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Sample records for oyi vaccinated macaques

  1. Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

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    Sparger, Ellen E.; Dubie, Robert A.; Shacklett, Barbara L.; Cole, Kelly S.; Chang, W.L.; Luciw, Paul A.

    2008-01-01

    Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-γ enzyme-linked immunospot responses of low magnitude were observed after immunization with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus

  2. Inactivated polio vaccination using a microneedle patch is immunogenic in the rhesus macaque.

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    Edens, Chris; Dybdahl-Sissoko, Naomi C; Weldon, William C; Oberste, M Steven; Prausnitz, Mark R

    2015-09-08

    The phased replacement of oral polio vaccine (OPV) with inactivated polio vaccine (IPV) is expected to significantly complicate mass vaccination campaigns, which are an important component of the global polio eradication endgame strategy. To simplify mass vaccination with IPV, we developed microneedle patches that are easy to administer, have a small package size, generate no sharps waste and are inexpensive to manufacture. When administered to rhesus macaques, neutralizing antibody titers were equivalent among monkeys vaccinated using microneedle patches and conventional intramuscular injection for IPV types 1 and 2. Serologic response to IPV type 3 vaccination was weaker after microneedle patch vaccination compared to intramuscular injection; however, we suspect the administered type 3 dose was lower due to a flawed pre-production IPV type 3 analytical method. IPV vaccination using microneedle patches was well tolerated by the monkeys. We conclude that IPV vaccination using a microneedle patch is immunogenic in rhesus macaques and may offer a simpler method of IPV vaccination of people to facilitate polio eradication. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Histopathological observation of immunized rhesus macaques with plague vaccines after subcutaneous infection of Yersinia pestis.

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    Guang Tian

    Full Text Available In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270 and SV2 (200 µg F1 and 100 µg rV270 subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×10(6 CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague.

  4. Evaluation of recombinant influenza virus-simian immunodeficiency virus vaccines in macaques.

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    Sexton, Amy; De Rose, Robert; Reece, Jeanette C; Alcantara, Sheilajen; Loh, Liyen; Moffat, Jessica M; Laurie, Karen; Hurt, Aeron; Doherty, Peter C; Turner, Stephen J; Kent, Stephen J; Stambas, John

    2009-08-01

    There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.

  5. Virus-Like Particle Vaccination Protects Nonhuman Primates from Lethal Aerosol Exposure with Marburgvirus (VLP Vaccination Protects Macaques against Aerosol Challenges

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    John M. Dye

    2016-04-01

    Full Text Available Marburg virus (MARV was the first filovirus to be identified following an outbreak of viral hemorrhagic fever disease in Marburg, Germany in 1967. Due to several factors inherent to filoviruses, they are considered a potential bioweapon that could be disseminated via an aerosol route. Previous studies demonstrated that MARV virus-like particles (VLPs containing the glycoprotein (GP, matrix protein VP40 and nucleoprotein (NP generated using a baculovirus/insect cell expression system could protect macaques from subcutaneous (SQ challenge with multiple species of marburgviruses. In the current study, the protective efficacy of the MARV VLPs in conjunction with two different adjuvants: QS-21, a saponin derivative, and poly I:C against homologous aerosol challenge was assessed in cynomolgus macaques. Antibody responses against the GP antigen were equivalent in all groups receiving MARV VLPs irrespective of the adjuvant; adjuvant only-vaccinated macaques did not demonstrate appreciable antibody responses. All macaques were subsequently challenged with lethal doses of MARV via aerosol or SQ as a positive control. All MARV VLP-vaccinated macaques survived either aerosol or SQ challenge while animals administered adjuvant only exhibited clinical signs and lesions consistent with MARV disease and were euthanized after meeting the predetermined criteria. Therefore, MARV VLPs induce IgG antibodies recognizing MARV GP and VP40 and protect cynomolgus macaques from an otherwise lethal aerosol exposure with MARV.

  6. Altered response hierarchy and increased T-cell breadth upon HIV-1 conserved element DNA vaccination in macaques.

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    Viraj Kulkarni

    Full Text Available HIV sequence diversity and potential decoy epitopes are hurdles in the development of an effective AIDS vaccine. A DNA vaccine candidate comprising of highly conserved p24(gag elements (CE induced robust immunity in all 10 vaccinated macaques, whereas full-length gag DNA vaccination elicited responses to these conserved elements in only 5 of 11 animals, targeting fewer CE per animal. Importantly, boosting CE-primed macaques with DNA expressing full-length p55(gag increased both magnitude of CE responses and breadth of Gag immunity, demonstrating alteration of the hierarchy of epitope recognition in the presence of pre-existing CE-specific responses. Inclusion of a conserved element immunogen provides a novel and effective strategy to broaden responses against highly diverse pathogens by avoiding decoy epitopes, while focusing responses to critical viral elements for which few escape pathways exist.

  7. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques.

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    Borggren, Marie; Vinner, Lasse; Andresen, Betina Skovgaard; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara Laura; Sanders, Rogier W; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma Joanne; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Grand, Roger Le; Fomsgaard, Anders

    2013-07-19

    HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

  8. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

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    Roger Le Grand

    2013-07-01

    Full Text Available HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb. We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

  9. Characterization of a Cynomolgus Macaque Model of Pneumonic Plague for Evaluation of Vaccine Efficacy.

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    Fellows, Patricia; Price, Jessica; Martin, Shannon; Metcalfe, Karen; Krile, Robert; Barnewall, Roy; Hart, Mary Kate; Lockman, Hank

    2015-09-01

    The efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus macaques (CMs) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of Yersinia pestis strain Colorado 92. CMs were vaccinated with a range of rF1V doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. The humoral immune response following vaccination was evaluated with anti-rF1, anti-rV, and anti-rF1V bridge enzyme-linked immunosorbent assays (ELISAs). Animals were challenged via aerosol exposure on day 149. Vaccine doses and antibody responses were each significantly associated with the probability of CM survival (P plague in a dose-dependent manner. There were statistically significant correlations between the vaccine dose and the time to onset of fever (P < 0.0001), the time from onset of fever to death (P < 0.0001), the time to onset of elevated respiratory rate (P = 0.0003), and the time to onset of decreased activity (P = 0.0251) postinfection in animals exhibiting these clinical signs. Delays in the onset of these clinical signs of disease were associated with larger doses of rF1V. Immunization with ≥ 12 μg of rF1V resulted in 100% CM survival. Since both the vaccine dose and anti-rF1V antibody titers correlate with survival, rF1V bridge ELISA titers can be used as a correlate of protection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Immunogenicity of DNA vaccines encoding simian immunodeficiency virus antigen targeted to dendritic cells in rhesus macaques.

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    Matthias Tenbusch

    Full Text Available BACKGROUND: Targeting antigens encoded by DNA vaccines to dendritic cells (DCs in the presence of adjuvants enhances their immunogenicity and efficacy in mice. METHODOLOGY/PRINCIPAL FINDINGS: To explore the immunogenicity of this approach in non-human primates, we generated a single chain antibody to the antigen uptake receptor DEC-205 expressed on rhesus macaque DCs. DNA vaccines encoding this single chain antibody fused to the SIV capsid protein were delivered to six monkeys each by either intramuscular electroporation or conventional intramuscular injection co-injected or not with poly ICLC, a stabilized poly I: C analogue, as adjuvant. Antibodies to capsid were induced by the DC-targeting and non-targeting control DNA delivered by electroporation while conventional DNA immunization at a 10-fold higher dose of DNA failed to induce detectable humoral immune responses. Substantial cellular immune responses were also observed after DNA electroporation of both DNAs, but stronger responses were induced by the non-targeting vaccine. Conventional immunization with the DC-targeting DNA at a 10-fold higher dose did not give rise to substantial cellular immune responses, neither when co-injected with poly ICLC. CONCLUSIONS/SIGNIFICANCE: The study confirms the potent immunogenicity of DNA vaccines delivered by electroporation. Targeting the DNA via a single chain antibody to DEC-205 expressed by DCs, however, does not improve the immunogenicity of the antigens in non-human primates.

  11. Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection.

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    Nakayama, Misako; Ozaki, Hiroichi; Itoh, Yasushi; Soda, Kosuke; Ishigaki, Hirohito; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Park, Chun-Ho; Tsuchiya, Hideaki; Kida, Hiroshi; Ogasawara, Kazumasa

    2016-12-01

    H9N2 avian influenza virus causes sporadic human infection. Since humans do not possess acquired immunity specific to this virus, we examined the pathogenicity of an H9N2 virus isolated from a human and then analyzed protective effects of a vaccine in cynomolgus macaques. After intranasal challenge with A/Hong Kong/1073/1999 (H9N2) (HK1073) isolated from a human patient, viruses were isolated from nasal and tracheal swabs in unvaccinated macaques with mild fever and body weight loss. A formalin-inactivated H9N2 whole particle vaccine derived from our virus library was subcutaneously inoculated to macaques. Vaccination induced viral antigen-specific IgG and neutralization activity in sera. After intranasal challenge with H9N2, the virus was detected only the day after inoculation in the vaccinated macaques. Without vaccination, many bronchus-associated lymphoid tissues (BALTs) were formed in the lungs after infection, whereas the numbers of BALTs were smaller and the cytokine responses were weaker in the vaccinated macaques than those in the unvaccinated macaques. These findings indicate that the H9N2 avian influenza virus HK1073 is pathogenic in primates but seems to cause milder symptoms than does H7N9 influenza virus as found in our previous studies and that a formalin-inactivated H9N2 whole particle vaccine induces protective immunity against H9N2 virus. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  12. Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV.

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    Chie Sugimoto

    Full Text Available HIV vaccine development has been hampered by issues such as undefined correlates of protection and extensive diversity of HIV. We addressed these issues using a previously established SIV-macaque model in which SIV mutants with deletions of multiple gp120 N-glycans function as potent live attenuated vaccines to induce near-sterile immunity against the parental pathogenic SIVmac239. In this study, we investigated the protective efficacy of these mutants against a highly pathogenic heterologous SIVsmE543-3 delivered intravenously to rhesus macaques with diverse MHC genotypes. All 11 vaccinated macaques contained the acute-phase infection with blood viral loads below the level of detection between 4 and 10 weeks postchallenge (pc, following a transient but marginal peak of viral replication at 2 weeks in only half of the challenged animals. In the chronic phase, seven vaccinees contained viral replication for over 80 weeks pc, while four did not. Neutralizing antibodies against challenge virus were not detected. Although overall levels of SIV specific T cell responses did not correlate with containment of acute and chronic viral replication, a critical role of cellular responses in the containment of viral replication was suggested. Emergence of viruses with altered fitness due to recombination between the vaccine and challenge viruses and increased gp120 glycosylation was linked to the failure to control SIV. These results demonstrate the induction of effective protective immune responses in a significant number of animals against heterologous virus by infection with deglycosylated attenuated SIV mutants in macaques with highly diverse MHC background. These findings suggest that broad HIV cross clade protection is possible, even in hosts with diverse genetic backgrounds. In summary, results of this study indicate that deglycosylated live-attenuated vaccines may provide a platform for the elucidation of correlates of protection needed for a

  13. Contribution of nonneutralizing vaccine-elicited antibody activities to improved protective efficacy in rhesus macaques immunized with Tat/Env compared with multigenic vaccines.

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    Florese, Ruth H; Demberg, Thorsten; Xiao, Peng; Kuller, LaRene; Larsen, Kay; Summers, L Ebonita; Venzon, David; Cafaro, Aurelio; Ensoli, Barbara; Robert-Guroff, Marjorie

    2009-03-15

    Previously, chronic-phase protection against SHIV(89.6P) challenge was significantly greater in macaques primed with replicating adenovirus type 5 host range mutant (Ad5hr) recombinants encoding HIVtat and env and boosted with Tat and Env protein compared with macaques primed with multigenic adenovirus recombinants (HIVtat, HIVenv, SIVgag, SIVnef) and boosted with Tat, Env, and Nef proteins. The greater protection was correlated with Tat- and Env-binding Abs. Because the macaques lacked SHIV(89.6P)-neutralizing activity prechallenge, we investigated whether Ab-dependent cellular cytotoxicity (ADCC) and Ab-dependent cell-mediated viral inhibition (ADCVI) might exert a protective effect. We clearly show that Tat can serve as an ADCC target, although the Tat-specific activity elicited did not correlate with better protection. However, Env-specific ADCC activity was consistently higher in the Tat/Env group, with sustained cell killing postchallenge exhibited at higher levels (p vaccine regimens.

  14. Long-term immunogenicity studies of formalin-inactivated enterovirus 71 whole-virion vaccine in macaques.

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    Chia-Chyi Liu

    Full Text Available Enterovirus 71 (EV71 has caused epidemics of hand, foot and mouth diseases in Asia during the past decades and no vaccine is available. A formalin-inactivated EV71 candidate vaccine (EV71vac based on B4 subgenotype has previously been developed and found to elicit strong neutralizing antibody responses in mice and humans. In this study, we evaluated the long-term immunogenicity and safety of this EV71vac in a non-human primate model. Juvenile macaques were immunized at 0, 3 and 6 weeks either with 10 or 5 µg doses of EV71vac formulated with AlPO4 adjuvant, or PBS as control. During the 56 weeks of studies, no fever nor local redness and swelling at sites of injections was observed in the immunized macaques. After single immunization, 100% seroconversion based on 4-fold increased in neutralization titer (Nt was detected in EV71vac immunized monkeys but not PBS controls. A dose-dependent IgG antibody response was observed in monkeys receiving EV71vac immunization. The Nt of EV71vac immunized macaques had reached the peak after 3 vaccinations, then decreased gradually; however, the GMT of neutralizing antibody in the EV71vac immunized macaques were still above 100 at the end of the study. Correspondingly, both dose- and time-dependent interferon-γ and CD4+ T cell responses were detected in monkeys receiving EV71vac. Interestingly, similar to human responses, the dominant T cell epitopes of macaques were identified mainly in VP2 and VP3 regions. In addition, strong cross-neutralizing antibodies against most EV71 subgenotypes except some C2 and C4b strains, and Coxsackievirus A16 were observed. In summary, our results indicate that EV71vac elicits dose-dependent T-cell and antibody responses in macaques that could be a good animal model for evaluating the long-term immune responses elicited by EV71 vaccines.

  15. Association of TLR7 variants with AIDS-like disease and AIDS vaccine efficacy in rhesus macaques.

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    Roman A Siddiqui

    Full Text Available In HIV infection, TLR7-triggered IFN-α production exerts a direct antiviral effect through the inhibition of viral replication, but may also be involved in immune pathogenesis leading to AIDS. TLR7 could also be an important mediator of vaccine efficacy. In this study, we analyzed polymorphisms in the X-linked TLR7 gene in the rhesus macaque model of AIDS. Upon resequencing of the TLR7 gene in 36 rhesus macaques of Indian origin, 12 polymorphic sites were detected. Next, we identified three tightly linked single nucleotide polymorphisms (SNP as being associated with survival time. Genotyping of 119 untreated, simian immunodeficiency virus (SIV-infected male rhesus macaques, including an 'MHC adjusted' subset, revealed that the three TLR7 SNPs are also significantly associated with set-point viral load. Surprisingly, this effect was not observed in 72 immunized SIV-infected male monkeys. We hypothesize (i that SNP c.13G>A in the leader peptide is causative for the observed genotype-phenotype association and that (ii the underlying mechanism is related to RNA secondary structure formation. Therefore, we investigated a fourth SNP (c.-17C>T, located 17 bp upstream of the ATG translation initiation codon, that is also potentially capable of influencing RNA structure. In c.13A carriers, neither set-point viral load nor survival time were related to the c.-17C>T genotype. In c.13G carriers, by contrast, the c.-17C allele was significantly associated with prolonged survival. Again, no such association was detected among immunized SIV-infected macaques. Our results highlight the dual role of TLR7 in immunodeficiency virus infection and vaccination and imply that it may be important to control human AIDS vaccine trials, not only for MHC genotype, but also for TLR7 genotype.

  16. Longitudinal study to assess the safety and efficacy of a live-attenuated SHIV vaccine in long term immunized rhesus macaques

    International Nuclear Information System (INIS)

    Yankee, Thomas M.; Sheffer, Darlene; Liu Zhengian; Dhillon, Sukhbir; Jia Fenglan; Chebloune, Yahia; Stephens, Edward B.; Narayan, Opendra

    2009-01-01

    Live-attenuated viruses derived from SIV and SHIV have provided the most consistent protection against challenge with pathogenic viruses, but concerns regarding their long-term safety and efficacy have hampered their clinical usefulness. We report a longitudinal study in which we evaluated the long-term safety and efficacy of ΔvpuSHIV PPC , a live virus vaccine derived from SHIV PPC . Macaques were administered two inoculations of ΔvpuSHIV PPC , three years apart, and followed for eight years. None of the five vaccinated macaques developed an AIDS-like disease from the vaccine. At eight years, macaques were challenged with pathogenic SIV and SHIV. None of the four macaques with detectable cellular-mediated immunity prior to challenge had detectable viral RNA in the plasma. This study demonstrates that multiple inoculations of a live vaccine virus can be used safely and can significantly extend the efficacy of the vaccine, as compared to a single inoculation, which is efficacious for approximately three years

  17. Effect of complement Factor H on anti-FHbp serum bactericidal antibody responses of infant rhesus macaques boosted with a licensed meningococcal serogroup B vaccine.

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    Giuntini, Serena; Beernink, Peter T; Granoff, Dan M

    2015-12-16

    FHbp is a major serogroup B meningococcal vaccine antigen. Binding of complement Factor H (FH) to FHbp is specific for human and some non-human primate FH. In previous studies, FH binding to FHbp vaccines impaired protective anti-FHbp antibody responses. In this study we investigated anti-FHbp antibody responses to a third dose of a licensed serogroup B vaccine (MenB-4C) in infant macaques vaccinated in a previous study with MenB-4C. Six macaques with high binding of FH to FHbp (FH(high)), and six with FH(low) baseline phenotypes, were immunized three months after dose 2. After dose 2, macaques with the FH(low) baseline phenotype had serum anti-FHbp antibodies that enhanced FH binding to FHbp (functionally converting them to a FH(high) phenotype). In this group, activation of the classical complement pathway (C4b deposition) by serum anti-FHbp antibody, and anti-FHbp serum bactericidal titers were lower after dose 3 than after dose 2 (pb deposition and bactericidal titers were similar after doses 2 and 3. Two macaques developed serum anti-FH autoantibodies after dose 2, which were not detected after dose 3. In conclusion, in macaques with the FH(low) baseline phenotype whose post-dose 2 serum anti-FHbp antibodies had converted them to FH(high), the anti-FHbp antibody repertoire to dose 3 was skewed to less protective epitopes than after dose 2. Mutant FHbp vaccines that eliminate FH binding may avoid eliciting anti-FHbp antibodies that enhance FH binding, and confer greater protection with less risk of inducing anti-FH autoantibodies than FHbp vaccines that bind FH. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen.

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    Grimaldi, Gabriel; Teva, Antonio; Porrozzi, Renato; Pinto, Marcelo A; Marchevsky, Renato S; Rocha, Maria Gabrielle L; Dutra, Miriam S; Bruña-Romero, Oscar; Fernandes, Ana-Paula; Gazzinelli, Ricardo T

    2014-06-01

    Visceral leishmaniasis (VL) is a severe vector-born disease of humans and dogs caused by Leishmania donovani complex parasites. Approximately 0.2 to 0.4 million new human VL cases occur annually worldwide. In the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. Thus, a prophylactic vaccine appears to be essential for VL control. The current efforts to develop an efficacious vaccine include the use of animal models that are as close to human VL. We have previously reported a L. infantum-macaque infection model that is reliable to determine which vaccine candidates are most worthy for further development. Among the few amastigote antigens tested so far, one of specific interest is the recombinant A2 (rA2) protein that protects against experimental L. infantum infections in mice and dogs. Primates were vaccinated using three rA2-based prime-boost immunization regimes: three doses of rA2 plus recombinant human interleukin-12 (rhIL-12) adsorbed in alum (rA2/rhIL-12/alum); two doses of non-replicative adenovirus recombinant vector encoding A2 (Ad5-A2) followed by two boosts with rA2/rhIL-12/alum (Ad5-A2+rA2/rhIL12/alum); and plasmid DNA encoding A2 gene (DNA-A2) boosted with two doses of Ad5-A2 (DNA-A2+Ad5-A2). Primates received a subsequent infectious challenge with L. infantum. Vaccines, apart from being safe, were immunogenic as animals responded with increased pre-challenge production of anti-A2-specific IgG antibodies, though with some variability in the response, depending on the vaccine formulation/protocol. The relative parasite load in the liver was significantly lower in immunized macaques as compared to controls. Protection correlated with hepatic granuloma resolution, and reduction of clinical symptoms, particularly when primates were vaccinated with the Ad5-A2+rA2/rhIL12/alum protocol. The remarkable clinical protection induced by A2 in an animal model that is

  19. Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen.

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    Gabriel Grimaldi

    2014-06-01

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is a severe vector-born disease of humans and dogs caused by Leishmania donovani complex parasites. Approximately 0.2 to 0.4 million new human VL cases occur annually worldwide. In the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. Thus, a prophylactic vaccine appears to be essential for VL control. The current efforts to develop an efficacious vaccine include the use of animal models that are as close to human VL. We have previously reported a L. infantum-macaque infection model that is reliable to determine which vaccine candidates are most worthy for further development. Among the few amastigote antigens tested so far, one of specific interest is the recombinant A2 (rA2 protein that protects against experimental L. infantum infections in mice and dogs. METHODOLOGY/PRINCIPAL FINDINGS: Primates were vaccinated using three rA2-based prime-boost immunization regimes: three doses of rA2 plus recombinant human interleukin-12 (rhIL-12 adsorbed in alum (rA2/rhIL-12/alum; two doses of non-replicative adenovirus recombinant vector encoding A2 (Ad5-A2 followed by two boosts with rA2/rhIL-12/alum (Ad5-A2+rA2/rhIL12/alum; and plasmid DNA encoding A2 gene (DNA-A2 boosted with two doses of Ad5-A2 (DNA-A2+Ad5-A2. Primates received a subsequent infectious challenge with L. infantum. Vaccines, apart from being safe, were immunogenic as animals responded with increased pre-challenge production of anti-A2-specific IgG antibodies, though with some variability in the response, depending on the vaccine formulation/protocol. The relative parasite load in the liver was significantly lower in immunized macaques as compared to controls. Protection correlated with hepatic granuloma resolution, and reduction of clinical symptoms, particularly when primates were vaccinated with the Ad5-A2+rA2/rhIL12/alum protocol. CONCLUSIONS

  20. Longitudinal multiparameter single-cell analysis of macaques immunized with pneumococcal protein-conjugated or unconjugated polysaccharide vaccines reveals distinct antigen specific memory B cell repertoires.

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    Bin Jia

    Full Text Available The efficacy of protein-conjugated pneumococcal polysaccharide vaccines has been well characterized for children. The level of protection conferred by unconjugated polysaccharide vaccines remains less clear, particularly for elderly individuals who have had prior antigenic experience through immunization with unconjugated polysaccharide vaccines or natural exposure to Streptococcus pneumoniae.We compared the magnitude, diversity and genetic biases of antigen-specific memory B cells in two groups of adult cynomolgus macaques that were immunized with a 7-valent conjugated vaccine and boosted after five years with either a 13-valent pneumococcal polysaccharide conjugate vaccine (13vPnC or a 23-valent unconjugated pneumococcal polysaccharide vaccine (23vPS using microengraving (a single-cell analysis method and single-cell RT-PCR.Seven days after boosting, the mean frequency of antigen-specific memory B cells was significantly increased in macaques vaccinated with 13vPnC compared to those receiving 23vPS. The 13vPnC-vaccinated macaques also exhibited a more even distribution of antibody specificities to four polysaccharides in the vaccine (PS4, 6B, 14, 23F that were examined. However, single-cell analysis of the antibody variable region sequences from antigen-specific B cells elicited by unconjugated and conjugated vaccines indicated that both the germline gene segments forming the heavy chains and the average lengths of the Complementary Determining Region 3 (CDR3 were similar.Our results confirm that distinctive differences can manifest between antigen-specific memory B cell repertoires in nonhuman primates immunized with conjugated and unconjugated pneumococcal polysaccharide vaccines. The study also supports the notion that the conjugated vaccines have a favorable profile in terms of both the frequency and breadth of the anamnestic response among antigen-specific memory B cells.

  1. Using Hematology Data from Malaria Vaccine Research Trials in Humans and Rhesus Macaques (Macaca mulatta) To Guide Volume Limits for Blood Withdrawal.

    Science.gov (United States)

    Hegge, Sara R; Hickey, Bradley W; Mcgrath, Shannon M; Stewart, V Ann

    2016-12-01

    Guidelines on safe volume limits for blood collection from research participants in both humans and laboratory animals vary widely between institutions. The main adverse event that may be encountered in large blood volume withdrawal is iron-deficiency anemia. Monitoring various parameters in a standard blood panel may help to prevent this outcome. To this end, we analyzed the Hgb and MCV values from 43 humans and 46 macaques in malaria vaccine research trials. Although the percentage of blood volume removed was greater for macaques than humans, macaques demonstrated an overall increase of MCV over time, indicating the ability to respond appropriately to frequent volume withdrawals. In contrast, humans showed a consistent declining trend in MCV. These declines in human MCV and Hgb were significant from the beginning to end of the study despite withdrawals that were smaller than recommended volume limits. Limiting the volume withdrawn to no more than 12.5% seemed to be sufficient for macaques, and at 14% or more individual animals tended to fail to respond appropriately to large-volume blood loss, as demonstrated by a decrease in MCV. The overall positive erythropoietic response seen in macaques was likely due to the controlled, iron-fortified diet they received. The lack of erythropoietic response in the human subjects may warrant iron supplementation or reconsideration of current blood volume withdrawal guidelines.

  2. Prime-Boost Vaccination Using Chemokine-Fused gp120 DNA and HIV Envelope Peptides Activates Both Immediate and Long-Term Memory Cellular Responses in Rhesus Macaques

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    Hong Qin

    2010-01-01

    Full Text Available HIV vaccine candidates with improved immunogenicity and induction of mucosal T-cell immunity are needed. A prime-boost strategy using a novel HIV glycoprotein 120 DNA vaccine was employed to immunize rhesus macaques. The DNA vaccine encoded a chimeric gp120 protein in fusion with monocyte chemoattractant protein-3, which was hypothesized to improve the ability of antigen-presenting cells to capture viral antigen through chemokine receptor-mediated endocytosis. DNA vaccination induced virus-reactive T cells in peripheral blood, detectable by T cell proliferation, INFγ ELISPOT and sustained IL-6 production, without humoral responses. With a peptide-cocktail vaccine containing a set of conserved polypeptides of HIV-1 envelope protein, given by nasogastric administration, primed T-cell immunity was significantly boosted. Surprisingly, long-term and peptide-specific mucosal memory T-cell immunity was detected in both vaccinated macaques after one year. Therefore, data from this investigation offer proof-of-principle for potential effectiveness of the prime-boost strategy with a chemokine-fused gp120 DNA and warrant further testing in the nonhuman primate models for developing as a potential HIV vaccine candidate in humans.

  3. Aerosol measles vaccination in macaques: Preclinical studies of immune responses and safety

    NARCIS (Netherlands)

    R.L. de Swart (Rik); T. Kuiken (Thijs); J. Fernandez-de Castro (Jorge); M.J. Papania (Mark); J.V. Bennett (John); J.L. Valdespino (José); P.D. Minor; C.L. Witham (Clyde); S. Yüksel (Selma); H.W. Vos (Helma); G. van Amerongen (Geert); A.D.M.E. Osterhaus (Albert)

    2006-01-01

    textabstractThe comparative efficacy and safety of measles vaccination via the aerosol route versus subcutaneous injection has not been fully resolved. We vaccinated cynomolgus monkeys (Macaca fascicularis) with the live-attenuated Edmonston-Zagreb measles virus (MV) vaccine and compared different

  4. Vaccination with Plasmodium knowlesi AMA1 formulated in the novel adjuvant co-vaccine HT™ protects against blood-stage challenge in rhesus macaques.

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    Muzamil Mahdi Abdel Hamid

    Full Text Available Plasmodium falciparum apical membrane antigen 1 (PfAMA1 is a leading blood stage vaccine candidate. Plasmodium knowlesi AMA1 (PkAMA1 was produced and purified using similar methodology as for clinical grade PfAMA1 yielding a pure, conformational intact protein. Combined with the adjuvant CoVaccine HT™, PkAMA1 was found to be highly immunogenic in rabbits and the efficacy of the PkAMA1 was subsequently tested in a rhesus macaque blood-stage challenge model. Six rhesus monkeys were vaccinated with PkAMA1 and a control group of 6 were vaccinated with PfAMA1. A total of 50 µg AMA1 was administered intramuscularly three times at 4 week intervals. One of six rhesus monkeys vaccinated with PkAMA1 was able to control parasitaemia, upon blood stage challenge with P. knowlesi H-strain. Four out of the remaining five showed a delay in parasite onset that correlated with functional antibody titres. In the PfAMA1 vaccinated control group, five out of six animals had to be treated with antimalarials 8 days after challenge; one animal did not become patent during the challenge period. Following a rest period, animals were boosted and challenged again. Four of the six rhesus monkeys vaccinated with PkAMA1 were able to control the parasitaemia, one had a delayed onset of parasitaemia and one animal was not protected, while all control animals required treatment. To confirm that the control of parasitaemia was AMA1-related, animals were allowed to recover, boosted and re-challenged with P. knowlesi Nuri strain. All control animals had to be treated with antimalarials by day 8, while five out of six PkAMA1 vaccinated animals were able to control parasitaemia. This study shows that: i Yeast-expressed PkAMA1 can protect against blood stage challenge; ii Functional antibody levels as measured by GIA correlated inversely with the day of onset and iii GIA IC(50 values correlated with estimated in vivo growth rates.

  5. Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge.

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    Iskra Tuero

    2015-08-01

    Full Text Available Many viral infections, including HIV, exhibit sex-based pathogenic differences. However, few studies have examined vaccine-related sex differences. We compared immunogenicity and protective efficacy of monomeric SIV gp120 with oligomeric SIV gp140 in a pre-clinical rhesus macaque study and explored a subsequent sex bias in vaccine outcome. Each immunization group (16 females, 8 males was primed twice mucosally with replication-competent Ad-recombinants encoding SIVsmH4env/rev, SIV239gag and SIV239nefΔ1-13 and boosted twice intramuscularly with SIVmac239 monomeric gp120 or oligomeric gp140 in MF59 adjuvant. Controls (7 females, 5 males received empty Ad and MF59. Up to 9 weekly intrarectal challenges with low-dose SIVmac251 were administered until macaques became infected. We assessed vaccine-induced binding, neutralizing, and non-neutralizing antibodies, Env-specific memory B cells and plasmablasts/plasma cells (PB/PC in bone marrow and rectal tissue, mucosal Env-specific antibodies, and Env-specific T-cells. Post-challenge, only one macaque (gp140-immunized remained uninfected. However, SIV acquisition was significantly delayed in vaccinated females but not males, correlated with Env-specific IgA in rectal secretions, rectal Env-specific memory B cells, and PC in rectal tissue. These results extend previous correlations of mucosal antibodies and memory B cells with protective efficacy. The gp140 regimen was more immunogenic, stimulating elevated gp140 and cyclic V2 binding antibodies, ADCC and ADCP activities, bone marrow Env-specific PB/PC, and rectal gp140-specific IgG. However, immunization with gp120, the form of envelope immunogen used in RV144, the only vaccine trial to show some efficacy, provided more significant acquisition delay. Further over 40 weeks of follow-up, no gp120 immunized macaques met euthanasia criteria in contrast to 7 gp140-immunized and 2 control animals. Although males had higher binding antibodies than females, ADCC

  6. Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge.

    Science.gov (United States)

    Tuero, Iskra; Mohanram, Venkatramanan; Musich, Thomas; Miller, Leia; Vargas-Inchaustegui, Diego A; Demberg, Thorsten; Venzon, David; Kalisz, Irene; Kalyanaraman, V S; Pal, Ranajit; Ferrari, Maria Grazia; LaBranche, Celia; Montefiori, David C; Rao, Mangala; Vaccari, Monica; Franchini, Genoveffa; Barnett, Susan W; Robert-Guroff, Marjorie

    2015-08-01

    Many viral infections, including HIV, exhibit sex-based pathogenic differences. However, few studies have examined vaccine-related sex differences. We compared immunogenicity and protective efficacy of monomeric SIV gp120 with oligomeric SIV gp140 in a pre-clinical rhesus macaque study and explored a subsequent sex bias in vaccine outcome. Each immunization group (16 females, 8 males) was primed twice mucosally with replication-competent Ad-recombinants encoding SIVsmH4env/rev, SIV239gag and SIV239nefΔ1-13 and boosted twice intramuscularly with SIVmac239 monomeric gp120 or oligomeric gp140 in MF59 adjuvant. Controls (7 females, 5 males) received empty Ad and MF59. Up to 9 weekly intrarectal challenges with low-dose SIVmac251 were administered until macaques became infected. We assessed vaccine-induced binding, neutralizing, and non-neutralizing antibodies, Env-specific memory B cells and plasmablasts/plasma cells (PB/PC) in bone marrow and rectal tissue, mucosal Env-specific antibodies, and Env-specific T-cells. Post-challenge, only one macaque (gp140-immunized) remained uninfected. However, SIV acquisition was significantly delayed in vaccinated females but not males, correlated with Env-specific IgA in rectal secretions, rectal Env-specific memory B cells, and PC in rectal tissue. These results extend previous correlations of mucosal antibodies and memory B cells with protective efficacy. The gp140 regimen was more immunogenic, stimulating elevated gp140 and cyclic V2 binding antibodies, ADCC and ADCP activities, bone marrow Env-specific PB/PC, and rectal gp140-specific IgG. However, immunization with gp120, the form of envelope immunogen used in RV144, the only vaccine trial to show some efficacy, provided more significant acquisition delay. Further over 40 weeks of follow-up, no gp120 immunized macaques met euthanasia criteria in contrast to 7 gp140-immunized and 2 control animals. Although males had higher binding antibodies than females, ADCC and ADCP

  7. Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: role of SIV-specific CD8+ T cell responses.

    Science.gov (United States)

    Malkevitch, Nina V; Patterson, L Jean; Aldrich, M Kristine; Wu, Yichen; Venzon, David; Florese, Ruth H; Kalyanaraman, V S; Pal, Ranajit; Lee, Eun Mi; Zhao, Jun; Cristillo, Anthony; Robert-Guroff, Marjorie

    2006-09-15

    Previously, priming with replication-competent adenovirus-SIV multigenic vaccines and boosting with envelope subunits strongly protected 39% of rhesus macaques against rectal SIV(mac251) challenge. To evaluate protection durability, eleven of the protected and two SIV-infected unimmunized macaques that controlled viremia were re-challenged rectally with SIV(mac251). Strong protection was observed in 8/11 vaccinees, including two exhibiting protected macaques. Durable protection was associated with significantly increased SIV-specific ELISPOT responses and lymphoproliferative responses to p27 at re-challenge. After CD8 depletion, 2 of 8 re-challenged, protected vaccinees maintained protection against re-challenge.

  8. Tat protein vaccination of cynomolgus macaques influences SHIV-89.6P cy243 epitope variability.

    Science.gov (United States)

    Ridolfi, Barbara; Genovese, Domenico; Argentini, Claudio; Maggiorella, Maria Teresa; Sernicola, Leonardo; Buttò, Stefano; Titti, Fausto; Borsetti, Alessandra; Ensoli, Barbara

    2008-02-01

    In a previous study we showed that vaccination with the native Tat protein controlled virus replication in five out of seven monkeys against challenge with the simian human immunodeficiency virus (SHIV)-89.6P cy243 and that this protection correlated with T helper (Th)-1 response and cytotoxic T lymphocyte (CTL) activity. To address the evolution of the SHIV-89.6P cy243 both in control and vaccinated infected monkeys, the sequence of the human immunodeficiency virus (HIV)-1 Tat protein and the C2-V3 Env region of the proviral-DNA-derived clones were analyzed in both control and vaccinated but unprotected animals. We also performed analysis of the T cell epitope using a predictive epitope model taking into consideration the phylogeny of the variants. Our results suggest that even though the viral evolution observed in both groups of monkeys was directed toward variations in the major histocompatibility complex (MHC)-I epitopes, in the control animals it was associated with mutational escape of such epitopes. On the contrary, it is possible that viral evolution in the vaccinated monkeys was linked to mutations that arose to keep high the viral fitness. In the vaccinated animals the reduction of epitope variability, obtained prompting the immune system by vaccination and inducing a specific immunological response against virus, was able to reduce the emergence of escape mutants. Thus the intervention of host's selective forces in driving CTL escape mutants and in modulating viral fitness appeared to be different in the two groups of monkeys. We concluded that in the vaccinated unprotected animals, vaccination with the Tat protein induced a broad antiviral response, as demonstrated by the reduced ability to develop escape mutants, which is known to help in the control of viral replication.

  9. Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV in macaques vaccinated with replication-deficient viral vectors

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    Strasak Alexander

    2009-06-01

    Full Text Available Abstract Background We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens. Results Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p Conclusion The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.

  10. A novel trivalent HPV 16/18/58 vaccine with anti-HPV 16 and 18 neutralizing antibody responses comparable to those induced by the Gardasil quadrivalent vaccine in rhesus macaque model

    Directory of Open Access Journals (Sweden)

    Fei Yin

    2017-06-01

    Full Text Available Persistent infection with human papillomavirus (HPV is a key factor in the development of precancerous lesions and invasive cervical cancer. Prophylactic vaccines to immunize against HPV are an effective approach to reducing HPV related disease burden. In this study, we investigated the immunogenicity and dosage effect of a trivalent HPV 16/18/58 vaccine (3vHPV produced in Escherichia coli (E.coli, with Gardasil quadrivalent vaccine (4vHPV, Merck & Co. as a positive control. Sera collected from rhesus macaques vaccinated with three dosage formulations of 3vHPV (termed low-, mid-, and high-dosage formulations, respectively, and the 4vHPV vaccine were analyzed by both Pseudovirus-Based Neutralization Assay (PBNA and Enzyme-Linked Immunosorbent Assay (ELISA. Strong immune responses against HPV 16/18/58 were successfully elicited, and dosage-dependence was observed, with likely occurrence of immune interference between different L1-VLP antigens. HPV 16/18 specific neutralizing antibody (nAb and total immunoglobulin G (IgG antibody responses in rhesus macaques receiving 3vHPV at the three dosages tested were generally non-inferior to those observed in rhesus macaques receiving 4vHPV throughout the study period. Particularly, HPV 18 nAb titers induced by the mid-dosage formulation that contained the same amounts of HPV 16/18 L1-VLPs as Gardasil 4vHPV were between 7.3 to 12.7-fold higher compared to the positive control arm from weeks 24–64. The durability of antibody responses specific to HPV 16/18 elicited by 3vHPV vaccines was also shown to be non-inferior to that associated with Gardasil 4vHPV. Keywords: Human papillomavirus, HPV 16/18/58, GMTs, Trivalent, Immunogenicity

  11. Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques

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    Bryan C. Au

    2016-02-01

    Full Text Available Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag-specific responses through direct injections of recombinant lentivectors (LVs that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months—the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an “off-the-shelf” anti-cancer vaccine that could be made at large scale and injected into patients—even on an out-patient basis.

  12. Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques.

    Science.gov (United States)

    Au, Bryan C; Lee, Chyan-Jang; Lopez-Perez, Orlay; Foltz, Warren; Felizardo, Tania C; Wang, James C M; Huang, Ju; Fan, Xin; Madden, Melissa; Goldstein, Alyssa; Jaffray, David A; Moloo, Badru; McCart, J Andrea; Medin, Jeffrey A

    2016-02-19

    Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag)-specific responses through direct injections of recombinant lentivectors (LVs) that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA)-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months-the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an "off-the-shelf" anti-cancer vaccine that could be made at large scale and injected into patients-even on an out-patient basis.

  13. Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine?

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    Xiao-Hong Li

    Full Text Available Rhesus macaques are unusual among schistosome hosts, self-curing from an established infection and thereafter manifesting solid immunity against a challenge, an ideal model for vaccine development. Previously, the immunological basis of self-cure was confirmed; surviving worms had ceased feeding but how immunological pressure achieved this was unclear. The schistosome esophagus is not simply a conduit for blood but plays a central role in its processing. Secretions from the anterior and posterior esophageal glands mix with incoming blood causing erythrocyte lysis and tethering and killing of leucocytes.We have analysed the self-cure process in rhesus macaques infected with Schistosoma japonicum. Faecal egg output and circulating antigen levels were used to chart the establishment of a mature worm population and its subsequent demise. The physiological stress of surviving females at perfusion was especially evident from their pale, shrunken appearance, while changes in the structure and function of the esophagus were observed in both sexes. In the anterior region electron microscopy revealed that the vesicle secretory process was disrupted, the tips of lining corrugations being swollen by greatly enlarged vesicles and the putative sites of vesicle release obscured by intense deposits of IgG. The lumen of the posterior esophagus in starving worms was occluded by cellular debris and the lining cytoplasmic plates were closely adherent, also potentially preventing secretion. Seven proteins secreted by the posterior gland were identified and IgG responses were detected to some or all of them. Intrinsic rhesus IgG colocalized with secreted SjMEGs 4.1, 8.2, 9, 11 and VAL-7 on cryosections, suggesting they are potential targets for disruption of function.Our data suggest that rhesus macaques self-cure by blocking esophagus function with antibody; the protein products of the glands provide a new class of potential vaccine targets.

  14. Prior DNA immunization enhances immune response to dominant and subdominant viral epitopes induced by a fowlpox-based SIVmac vaccine in long-term slow-progressor macaques infected with SIVmac251

    International Nuclear Information System (INIS)

    Radaelli, Antonia; Nacsa, Janos; Tsai, W.-P.; Edghill-Smith, Yvette; Zanotto, Carlo; Elli, Veronica; Venzon, David; Tryniszewska, Elzbieta; Markham, Phil; Mazzara, Gail P.; Panicali, Dennis; Morghen, Carlo De Giuli; Franchini, Genoveffa

    2003-01-01

    A therapeutic vaccine for individuals infected with HIV-1 and treated with antiretroviral therapy (ART) should be able to replenish virus-specific CD4+ T-cells and broaden the virus-specific CD8+ T-cell response in order to maintain CD8+ T-cell function and minimize viral immune escape after ART cessation. Because a combination of DNA and recombinant poxvirus vaccine modalities induces high levels of virus-specific CD4+ T-cell response and broadens the cytolytic activity in naive macaques, we investigated whether the same results could be obtained in SIVmac251-infected macaques. The macaques studied here were long-term nonprogressors that naturally contained viremia but were nevertheless treated with a combination of antiviral drugs to assess more carefully the effect of vaccination in the context of ART. The combination of a DNA expressing the gag and pol genes (DNA-SIV-gp) of SIVmac239 followed by a recombinant fowlpox expressing the same SIVmac genes (FP-SIV-gp) was significantly more immunogenic than two immunizations of FP-SIV-gp in SIVmac251-infected macaques treated with ART. The DNA/FP combination significantly expanded and broadened Gag-specific T-cell responses measured by tetramer staining, ELISPOT, and intracellular cytokine staining and measurement of ex vivo cytolytic function. Importantly, the combination of these vaccine modalities also induced a sizeable expansion in most macaques of Gag-specific CD8-(CD4+) T-cells able to produce TNF-α. Hopefully, this modality of vaccine combination may be useful in the clinical management of HIV-1-infected individuals

  15. Vaccine induced antibodies to the first variable loop of human immunodeficiency virus type 1 gp120, mediate antibody-dependent virus inhibition in macaques.

    Science.gov (United States)

    Bialuk, Izabela; Whitney, Stephen; Andresen, Vibeke; Florese, Ruth H; Nacsa, Janos; Cecchinato, Valentina; Valeri, Valerio W; Heraud, Jean-Michel; Gordon, Shari; Parks, Robyn Washington; Montefiori, David C; Venzon, David; Demberg, Thorsten; Guroff, Marjorie Robert-; Landucci, Gary; Forthal, Donald N; Franchini, Genoveffa

    2011-12-09

    The role of antibodies directed against the hyper variable envelope region V1 of human immunodeficiency virus type 1 (HIV-1), has not been thoroughly studied. We show that a vaccine able to elicit strain-specific non-neutralizing antibodies to this region of gp120 is associated with control of highly pathogenic chimeric SHIV(89.6P) replication in rhesus macaques. The vaccinated animal that had the highest titers of antibodies to the amino terminus portion of V1, prior to challenge, had secondary antibody responses that mediated cell killing by antibody-dependent cellular cytotoxicity (ADCC), as early as 2 weeks after infection and inhibited viral replication by antibody-dependent cell-mediated virus inhibition (ADCVI), by 4 weeks after infection. There was a significant inverse correlation between virus level and binding antibody titers to the envelope protein, (R=-0.83, p=0.015), and ADCVI (R=-0.84 p=0.044). Genotyping of plasma virus demonstrated in vivo selection of three SHIV(89.6P) variants with changes in potential N-linked glycosylation sites in V1. We found a significant inverse correlation between virus levels and titers of antibodies that mediated ADCVI against all the identified V1 virus variants. A significant inverse correlation was also found between neutralizing antibody titers to SHIV(89.6) and virus levels (R=-0.72 p=0.0050). However, passive inoculation of purified immunoglobulin from animal M316, the macaque that best controlled virus, to a naïve macaque, resulted in a low serum neutralizing antibodies and low ADCVI activity that failed to protect from SHIV(89.6P) challenge. Collectively, while our data suggest that anti-envelope antibodies with neutralizing and non-neutralizing Fc(R-dependent activities may be important in the control of SHIV replication, they also demonstrate that low levels of these antibodies alone are not sufficient to protect from infection. Published by Elsevier Ltd.

  16. Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV vaccinated rhesus macaques

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    Pahar Bapi

    2012-08-01

    Full Text Available Abstract Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV vector – simian immunodeficiency virus (SIV envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1. Findings The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals. Conclusions Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.

  17. Priming B cell-mediated anti-HIV envelope responses by vaccination allows for the long-term control of infection in macaques exposed to a R5-tropic SHIV

    International Nuclear Information System (INIS)

    Buckner, Clarisa; Gines, Leoned G.; Saunders, Cheryl J.; Vojtech, Lucia; Srivastava, Indresh; Gettie, Agegnehu; Bohm, Rudolph; Blanchard, James; Barnett, Susan W.; Safrit, Jeffrey T.; Stamatatos, Leonidas

    2004-01-01

    The potential of vaccine-elicited anti-HIV envelope antibodies to control HIV-infection was evaluated by immunizing macaques with the HIV envelope protein and transiently depleting them of their CD8+ cells before intravenous challenge with the pathogenic CCR5-tropic SIV/HIV chimeric virus, SHIV SF162P4 . Although sterilizing immunity was not achieved, all vaccinated animals effectively controlled infection and remained free of disease for the duration of observation (over 3 years). In contrast, during the same period, the control animals progressed to disease. Both the vaccinees and the controls developed robust cell-mediated antiviral and neutralizing antibody responses following infection. A comparative analysis of these responses suggests that the more effective long-term control of infection by the vaccinated animals is due to the more rapid development of anti-HIV envelope antibodies. These studies suggest that priming by vaccination of B cell anti-HIV envelope responses maybe crucial for the long-term control of HIV infection

  18. A tetravalent virus-like particle vaccine designed to display domain III of dengue envelope proteins induces multi-serotype neutralizing antibodies in mice and macaques which confer protection against antibody dependent enhancement in AG129 mice.

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    Viswanathan Ramasamy

    2018-01-01

    Full Text Available Dengue is one of the fastest spreading vector-borne diseases, caused by four antigenically distinct dengue viruses (DENVs. Antibodies against DENVs are responsible for both protection as well as pathogenesis. A vaccine that is safe for and efficacious in all people irrespective of their age and domicile is still an unmet need. It is becoming increasingly apparent that vaccine design must eliminate epitopes implicated in the induction of infection-enhancing antibodies.We report a Pichia pastoris-expressed dengue immunogen, DSV4, based on DENV envelope protein domain III (EDIII, which contains well-characterized serotype-specific and cross-reactive epitopes. In natural infection, <10% of the total neutralizing antibody response is EDIII-directed. Yet, this is a functionally relevant domain which interacts with the host cell surface receptor. DSV4 was designed by in-frame fusion of EDIII of all four DENV serotypes and hepatitis B surface (S antigen and co-expressed with unfused S antigen to form mosaic virus-like particles (VLPs. These VLPs displayed EDIIIs of all four DENV serotypes based on probing with a battery of serotype-specific anti-EDIII monoclonal antibodies. The DSV4 VLPs were highly immunogenic, inducing potent and durable neutralizing antibodies against all four DENV serotypes encompassing multiple genotypes, in mice and macaques. DSV4-induced murine antibodies suppressed viremia in AG129 mice and conferred protection against lethal DENV-4 virus challenge. Further, neither murine nor macaque anti-DSV4 antibodies promoted mortality or inflammatory cytokine production when passively transferred and tested in an in vivo dengue disease enhancement model of AG129 mice.Directing the immune response to a non-immunodominant but functionally relevant serotype-specific dengue epitope of the four DENV serotypes, displayed on a VLP platform, can help minimize the risk of inducing disease-enhancing antibodies while eliciting effective tetravalent

  19. Efficacy of an Adenovirus-based Anti-cocaine Vaccine to Reduce Cocaine Self-administration and Reacqusition using a Choice Procedure in Rhesus Macaques

    Science.gov (United States)

    Evans, Suzette M.; Foltin, Richard W.; Hicks, Martin J.; Rosenberg, Jonathan B.; De, Bishnu P.; Janda, Kim D.; Kaminsky, Stephen M.; Crystal, Ronald G.

    2016-01-01

    Immunopharmacotherapy offers an approach for treating cocaine abuse by specifically targeting the cocaine molecule and preventing its access to the CNS. dAd5GNE is a novel cocaine vaccine that attenuates the stimulant and the reinforcing effects of cocaine in rats. The goal of this study was to extend and validate dAd5GNE vaccine efficacy in non-human primates. Six experimentally naïve adult female rhesus monkeys (Macaca mulatta) were trained to self-administer 0.1 mg/kg/injection intravenous (i.v.) cocaine or receive candy; then 4 monkeys were administered the vaccine and 2 monkeys were administered vehicle intramuscularly, with additional vaccine boosts throughout the study. The reinforcing effects of cocaine were measured during self-administration, extinction, and reacquisition (relapse) phases. Serum antibody titers in the vaccinated monkeys remained high throughout the study. There was no change in the preference for cocaine over candy over a 20-week period in 5 of the 6 monkeys; only one of the 4 (25%) vaccinated monkeys showed a decrease in cocaine choice. All 6 monkeys extinguished responding for cocaine during saline extinction testing; vaccinated monkeys tended to take longer to extinguish responding than control monkeys (17.5 vs. 7.0 sessions). Vaccination substantially retarded reacquisition of cocaine self-administration; control monkeys resumed cocaine self-administration within 6–41 sessions and 1 vaccinated monkey resumed cocaine self-administration in 19 sessions. The other 3 vaccinated monkeys required between 57–94 sessions to resume cocaine self-administration even in the context of employing several manipulations to encourage cocaine reacquisition. These data suggest that the dAdGNE vaccine may have therapeutic potential for humans who achieve cocaine abstinence as part of a relapse prevention strategy. PMID:27697554

  20. Prior DNA vaccination does not interfere with the live-attenuated measles vaccine.

    Science.gov (United States)

    Premenko-Lanier, Mary; Rota, Paul; Rhodes, Gary; Bellini, William; McChesney, Michael

    2004-01-26

    The currently used live-attenuated measles vaccine is very effective although maternal antibody prevents its administration prior to 6 months of age. We are investigating the ability of a DNA vaccine encoding the measles viral hemagglutinin, fusion and nucleoprotein to protect newborn infants from measles. Here, we show that a measles DNA vaccine protects juvenile macaques from pathogenic measles virus challenge and that macaques primed and boosted with this DNA vaccine have anemnestic antibody and cell-mediated responses after vaccination with a live-attenuated canine distemper-measles vaccine. Therefore, this DNA vaccine administered to newborn infants may not hinder the subsequent use of live-attenuated measles vaccine.

  1. Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques.

    Directory of Open Access Journals (Sweden)

    Matthew T Aliota

    2016-12-01

    Full Text Available Zika virus (ZIKV; Flaviviridae, Flavivirus was declared a public health emergency of international concern by the World Health Organization (WHO in February 2016, because of the evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome in adults and congenital birth defects including microcephaly in the developing fetus. Because development of a ZIKV vaccine is a top research priority and because the genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, assessing whether immunity elicited against one ZIKV strain is sufficient to confer broad protection against all ZIKV strains is critical. Recently, in vitro studies demonstrated that ZIKV likely circulates as a single serotype. Here, we demonstrate that immunity elicited by African lineage ZIKV protects rhesus macaques against subsequent infection with Asian lineage ZIKV.Using our recently developed rhesus macaque model of ZIKV infection, we report that the prototypical ZIKV strain MR766 productively infects macaques, and that immunity elicited by MR766 protects macaques against heterologous Asian ZIKV. Furthermore, using next generation deep sequencing, we found in vivo restoration of a putative N-linked glycosylation site upon replication in macaques that is absent in numerous MR766 strains that are widely being used by the research community. This reversion highlights the importance of carefully examining the sequence composition of all viral stocks as well as understanding how passage history may alter a virus from its original form.An effective ZIKV vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses were primed by infection with East African ZIKV were completely protected from detectable viremia when subsequently rechallenged with heterologous Asian ZIKV. Therefore, these data suggest that immunogen selection is unlikely to adversely affect the breadth of

  2. Rational design of a live attenuated dengue vaccine: 2'-o-methyltransferase mutants are highly attenuated and immunogenic in mice and macaques.

    Directory of Open Access Journals (Sweden)

    Roland Züst

    Full Text Available Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue, resulting in a continuously increasing number of cases. A cost-effective, safe vaccine conferring protection with ideally a single injection could stop dengue transmission. Current vaccine candidates require several booster injections or do not provide protection against all four serotypes. Here we demonstrate that dengue virus mutants lacking 2'-O-methyltransferase activity are highly sensitive to type I IFN inhibition. The mutant viruses are attenuated in mice and rhesus monkeys and elicit a strong adaptive immune response. Monkeys immunized with a single dose of 2'-O-methyltransferase mutant virus showed 100% sero-conversion even when a dose as low as 1,000 plaque forming units was administrated. Animals were fully protected against a homologous challenge. Furthermore, mosquitoes feeding on blood containing the mutant virus were not infected, whereas those feeding on blood containing wild-type virus were infected and thus able to transmit it. These results show the potential of 2'-O-methyltransferase mutant virus as a safe, rationally designed dengue vaccine that restrains itself due to the increased susceptibility to the host's innate immune response.

  3. [VACCINES].

    Science.gov (United States)

    Bellver Capella, Vincente

    2015-10-01

    Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs.

  4. Efficient generation of monoclonal antibodies from single rhesus macaque antibody secreting cells.

    Science.gov (United States)

    Meng, Weixu; Li, Leike; Xiong, Wei; Fan, Xuejun; Deng, Hui; Bett, Andrew J; Chen, Zhifeng; Tang, Aimin; Cox, Kara S; Joyce, Joseph G; Freed, Daniel C; Thoryk, Elizabeth; Fu, Tong-Ming; Casimiro, Danilo R; Zhang, Ningyan; A Vora, Kalpit; An, Zhiqiang

    2015-01-01

    Nonhuman primates (NHPs) are used as a preclinical model for vaccine development, and the antibody profiles to experimental vaccines in NHPs can provide critical information for both vaccine design and translation to clinical efficacy. However, an efficient protocol for generating monoclonal antibodies from single antibody secreting cells of NHPs is currently lacking. In this study we established a robust protocol for cloning immunoglobulin (IG) variable domain genes from single rhesus macaque (Macaca mulatta) antibody secreting cells. A sorting strategy was developed using a panel of molecular markers (CD3, CD19, CD20, surface IgG, intracellular IgG, CD27, Ki67 and CD38) to identify the kinetics of B cell response after vaccination. Specific primers for the rhesus macaque IG genes were designed and validated using cDNA isolated from macaque peripheral blood mononuclear cells. Cloning efficiency was averaged at 90% for variable heavy (VH) and light (VL) domains, and 78.5% of the clones (n = 335) were matched VH and VL pairs. Sequence analysis revealed that diverse IGHV subgroups (for VH) and IGKV and IGLV subgroups (for VL) were represented in the cloned antibodies. The protocol was tested in a study using an experimental dengue vaccine candidate. About 26.6% of the monoclonal antibodies cloned from the vaccinated rhesus macaques react with the dengue vaccine antigens. These results validate the protocol for cloning monoclonal antibodies in response to vaccination from single macaque antibody secreting cells, which have general applicability for determining monoclonal antibody profiles in response to other immunogens or vaccine studies of interest in NHPs.

  5. Natural and cross-inducible anti-SIV antibodies in Mauritian cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Hongzhao Li

    Full Text Available Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10, respectively (PCS peptides, and three non-PCS Gag or Env peptides. Natural antibodies to SIV antigens were detected in subsets of monkeys. The antibody reactivity to SIV was further confirmed by Western blot using purified recombinant SIV Gag and Env proteins. As expected, the immunization of monkeys with PCS antigens elicited anti-PCS antibodies. However, unexpectedly, antibodies to non-PCS peptides were also induced, as shown by both Bio-Plex and Western blot analyses, while the non-PCS peptides do not share sequence homology with PCS peptides. The presence of natural and vaccine cross-inducible SIV antibodies in Mauritian cynomolgus macaques should be considered in animal selection, experimental design and result interpretation, for their best use in HIV vaccine research.

  6. Illegal trade in Barbary macaques

    NARCIS (Netherlands)

    van Uhm, Daan|info:eu-repo/dai/nl/380477025

    2014-01-01

    While Morocco is well known as the main port between Africa and the EU for the illegal drugs trade and migration, the illegal trade in wildlife is flourishing as well. Next to the illegal large-scale trafficking of tortoises and birds, it is estimated that as few as 5,000 Barbary macaques remain in

  7. Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.

    Directory of Open Access Journals (Sweden)

    J Gerardo García-Lerma

    2008-02-01

    Full Text Available In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission.We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC, group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF, and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4 received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively. All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected.This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities.

  8. Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid

    Science.gov (United States)

    Boyer, Jean D.; Robinson, Tara M.; Kutzler, Michele A.; Vansant, Gordon; Hokey, David A.; Kumar, Sanjeev; Parkinson, Rose; Wu, Ling; Sidhu, Maninder K.; Pavlakis, George N.; Felber, Barbara K.; Brown, Charles; Silvera, Peter; Lewis, Mark G.; Monforte, Joseph; Waldmann, Thomas A.; Eldridge, John; Weiner, David B.

    2007-01-01

    The cell-mediated immune profile induced by a recombinant DNA vaccine was assessed in the simian/HIV (SHIV) and macaque model. The vaccine strategy included coimmunization of a DNA-based vaccine alone or in combination with an optimized plasmid encoding macaque IL-15 (pmacIL-15). We observed strong induction of vaccine-specific IFN-γ-producing CD8+ and CD4+ effector T cells in the vaccination groups. Animals were subsequently challenged with 89.6p. The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone. Lymphocytes isolated from the group covaccinated with pmacIL-15 had higher cellular proliferative responses than lymphocytes isolated from the macaques that received SHIV DNA alone. Vaccine antigen activation of lymphocytes was also studied for a series of immunological molecules. Although mRNA for IFN-γ was up-regulated after antigen stimulation, the inflammatory molecules IL-8 and MMP-9 were down-regulated. These observed immune profiles are potentially reflective of the ability of the different groups to control SHIV replication. This study demonstrates that an optimized IL-15 immune adjuvant delivered with a DNA vaccine can impact the cellular immune profile in nonhuman primates and lead to enhanced suppression of viral replication. PMID:18000037

  9. Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa.

    Science.gov (United States)

    McCarthy, Kevin R; Johnson, Welkin E; Kirmaier, Andrea

    2016-01-01

    In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV) from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm). Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac) and pig-tailed macaques (SIVmne) have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa) were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery.

  10. Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa.

    Directory of Open Access Journals (Sweden)

    Kevin R McCarthy

    Full Text Available In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm. Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac and pig-tailed macaques (SIVmne have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery.

  11. Mucosal vaccination with heterologous viral vectored vaccine targeting subdominant SIV accessory antigens strongly inhibits early viral replication

    DEFF Research Database (Denmark)

    Xu, Huanbin; Andersson, Anne-Marie Carola; Ragonnaud, Emeline

    2017-01-01

    Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat...

  12. Memory immune responses against pandemic (H1N1 2009 influenza virus induced by a whole particle vaccine in cynomolgus monkeys carrying Mafa-A1*052:02.

    Directory of Open Access Journals (Sweden)

    Masahiko Arikata

    Full Text Available We made an H1N1 vaccine candidate from a virus library consisting of 144 ( = 16 HA×9 NA non-pathogenic influenza A viruses and examined its protective effects against a pandemic (2009 H1N1 strain using immunologically naïve cynomolgus macaques to exclude preexisting immunity and to employ a preclinical study since preexisting immunity in humans previously vaccinated or infected with influenza virus might make comparison of vaccine efficacy difficult. Furthermore, macaques carrying a major histocompatibility complex class I molecule, Mafa-A1*052:02, were used to analyze peptide-specific CD8(+ T cell responses. Sera of macaques immunized with an inactivated whole particle formulation without addition of an adjuvant showed higher neutralization titers against the vaccine strain A/Hokkaido/2/1981 (H1N1 than did sera of macaques immunized with a split formulation. Neutralization activities against the pandemic strain A/Narita/1/2009 (H1N1 in sera of macaques immunized twice with the split vaccine reached levels similar to those in sera of macaques immunized once with the whole particle vaccine. After inoculation with the pandemic virus, the virus was detected in nasal samples of unvaccinated macaques for 6 days after infection and for 2.67 days and 5.33 days on average in macaques vaccinated with the whole particle vaccine and the split vaccine, respectively. After the challenge infection, recall neutralizing antibody responses against the pandemic virus and CD8(+ T cell responses specific for nucleoprotein peptide NP262-270 bound to Mafa-A1*052:02 in macaques vaccinated with the whole particle vaccine were observed more promptly or more vigorously than those in macaques vaccinated with the split vaccine. These findings demonstrated that the vaccine derived from our virus library was effective for pandemic virus infection in macaques and that the whole particle vaccine conferred more effective memory and broader cross-reactive immune responses

  13. Comparative Pathology of Smallpox and Monkeypox in Man and Macaques

    Science.gov (United States)

    Cann, J. A.; Jahrling, P. B.; Hensley, L. E.; Wahl-Jensen, V.

    2012-01-01

    Summary In the three decades since the eradication of smallpox and cessation of routine vaccination, the collective memory of the devastating epidemics caused by this orthopoxvirus has waned, and the human population has become increasingly susceptible to a disease that remains high on the list of possible bioterrorism agents. Research using surrogate orthopoxviruses in their natural hosts, as well as limited variola virus research in animal models, continues worldwide; however, interpretation of findings is often limited by our relative lack of knowledge about the naturally occurring disease. For modern comparative pathologists, many of whom have no first-hand knowledge of naturally occurring smallpox, this work provides a contemporary review of this historical disease, as well as discussion of how it compares with human monkeypox and the corresponding diseases in macaques. PMID:22884034

  14. Expression, purification, crystallization and preliminary X-ray diffraction analysis of rhesus macaque CD8αα homodimer

    International Nuclear Information System (INIS)

    Zong, Lili; Chen, Yong; Yan, Jinghua; Zhang, Jianhua

    2010-01-01

    CD8α exodomain protein, a crucial immune-system factor in rhesus macaque (M. mulatta), one of the best animal models for vaccine design, was assembled and crystallized. The full structure data will contribute to future studies of immune responses in rhesus macaques. As a T-cell co-receptor, CD8 binds to MHC class I molecules and plays a pivotal role in the activation of cytotoxic T lymphocytes. To date, structures of CD8 have been solved for two different mammals: human and mouse. The infection of rhesus macaques (Macaca mulatta) by simian immunodeficiency virus (SIV) is the best animal model for studying HIV. In this study, the rhesus macaque CD8 (rCD8) αα homodimer was obtained and rCD8α exodomain protein crystals were successfully obtained for further structural analysis. Diffraction data were collected to a resolution of 2.4 Å. The crystal belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 46.52, b = 56.28, c = 82.40 Å. These data will facilitate further studies on the structural differences between these CD8 structures and the cellular immune responses of rhesus macaque

  15. Progression of pathogenic events in cynomolgus macaques infected with variola virus.

    Directory of Open Access Journals (Sweden)

    Victoria Wahl-Jensen

    Full Text Available Smallpox, caused by variola virus (VARV, is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

  16. Effect of Chronic Social Stress on Prenatal Transfer of Antitetanus Immunity in Captive Breeding Rhesus Macaques (Macaca mulatta).

    Science.gov (United States)

    Stammen, Rachelle L; Cohen, Joyce K; Meeker, Tracy L; Crane, Maria M; Amara, Rama R; Hicks, Sakeenah L; Meyer, Jerrold S; Ethun, Kelly F

    2018-05-15

    Because tetanus can cause significant morbidity and mortality in NHP, colonywide vaccination with tetanus toxoid is recommendedfor outdoor breeding colonies of rhesus macaques, with primary immunizations commonly given to infants at 6 mo of age followed by booster vaccines every 10 y. Maternal antibodies are thought to offer protective immunity to infants younger than 6 mo. However, historical colony data from the Yerkes National Primate Research Center show a higher incidence of tetanus among infants (≤ 6 mo old) born to subordinate dams. Whether this higher incidence of infantile tetanus is due to a higher incidence of trauma among subordinate animals or is a stress-induced impairment of maternal antibody protection is unknown. Studies in other NHP species suggest that chronic exposure to social stressors interferes with the receptor-mediated transplacental transfer of IgG. Therefore, the primary aim of this study was to determine whether chronic stress associated with social subordination impairs prenatal transfer of antitetanus immunity in breeding female rhesus macaques. Subjects included 26 high- and 26 low-ranking adult female rhesus macaques that were nearly 5 or 10 y after their initial immunization and their nonimmunized infants. We hypothesized that infants born to subordinate dams that were nearly 10 y after immunization would have the lowest infant-to-dam antibody ratios and thus would be at greatest risk for infection. Results revealed no significant intergroup differences in infant antitetanus IgG levels. However, infant-to-dam IgG ratios against tetanus were significantly lower among subordinate animals compared with dominant macaques, after accounting for the number of years since the dam's initial vaccination. In addition, higher maternal hair cortisol levels predicted lower infant-to-dam tetanus toxoid IgG ratios. Together, these findings suggest that chronic social stress in female rhesus macaques may hamper the prenatal transfer of

  17. Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques.

    Science.gov (United States)

    Coffey, Lark L; Pesavento, Patricia A; Keesler, Rebekah I; Singapuri, Anil; Watanabe, Jennifer; Watanabe, Rie; Yee, JoAnn; Bliss-Moreau, Eliza; Cruzen, Christina; Christe, Kari L; Reader, J Rachel; von Morgenland, Wilhelm; Gibbons, Anne M; Allen, A Mark; Linnen, Jeff; Gao, Kui; Delwart, Eric; Simmons, Graham; Stone, Mars; Lanteri, Marion; Bakkour, Sonia; Busch, Michael; Morrison, John; Van Rompay, Koen K A

    2017-01-01

    Animal models of Zika virus (ZIKV) are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. Humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. We inoculated 2 non-pregnant rhesus macaques with a 2015 Brazilian ZIKV strain. Consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias that cleared as neutralizing antibody developed. In 1 animal, viral RNA (vRNA) could be detected longer in whole blood than in plasma. Despite no major histopathologic changes, many adult tissues contained vRNA 14 days post-infection with highest levels in hemolymphatic tissues. These observations warrant further studies to investigate ZIKV persistence and its potential clinical implications for transmission via blood products or tissue and organ transplants.

  18. Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques.

    Directory of Open Access Journals (Sweden)

    Lark L Coffey

    Full Text Available Animal models of Zika virus (ZIKV are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. Humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. We inoculated 2 non-pregnant rhesus macaques with a 2015 Brazilian ZIKV strain. Consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias that cleared as neutralizing antibody developed. In 1 animal, viral RNA (vRNA could be detected longer in whole blood than in plasma. Despite no major histopathologic changes, many adult tissues contained vRNA 14 days post-infection with highest levels in hemolymphatic tissues. These observations warrant further studies to investigate ZIKV persistence and its potential clinical implications for transmission via blood products or tissue and organ transplants.

  19. X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide

    International Nuclear Information System (INIS)

    Feng, Youjun; Qi, Jianxun; Zhang, Huimin; Wang, Jinzi; Liu, Jinhua; Jiang, Fan; Gao, Feng

    2005-01-01

    X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide. Simian immunodeficiency virus (SIV) in the rhesus macaque is regarded as a classic animal model, playing a crucial role in HIV vaccine strategies and therapeutics by characterizing various cytotoxic T-lymphocyte (CTL) responses in macaque monkeys. However, the availability of well documented structural reports focusing on rhesus macaque major histocompatibility complex class I (MHC I) molecules remains extremely limited. Here, a complex of the rhesus macaque MHC I molecule (Mamu-A*02) with human β 2 m and an immunodominant SIV-Gag nonapeptide, GESNLKSLY (GY9), has been crystallized. The crystal diffracts X-rays to 2.7 Å resolution and belongs to space group C2, with unit-cell parameters a = 124.11, b = 110.45, c = 100.06 Å, and contains two molecules in the asymmetric unit. The availability of the structure, which is being solved by molecular replacement, will provide new insights into rhesus macaque MHC I (Mamu-A*02) presenting pathogenic SIV peptides

  20. X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Youjun [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate School, Chinese Academy of Sciences, Beijing (China); Qi, Jianxun [Graduate School, Chinese Academy of Sciences, Beijing (China); Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Zhang, Huimin; Wang, Jinzi [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Liu, Jinhua [College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China); Jiang, Fan [Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Gao, Feng, E-mail: gaofeng@im.ac.cn [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China)

    2006-01-01

    X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide. Simian immunodeficiency virus (SIV) in the rhesus macaque is regarded as a classic animal model, playing a crucial role in HIV vaccine strategies and therapeutics by characterizing various cytotoxic T-lymphocyte (CTL) responses in macaque monkeys. However, the availability of well documented structural reports focusing on rhesus macaque major histocompatibility complex class I (MHC I) molecules remains extremely limited. Here, a complex of the rhesus macaque MHC I molecule (Mamu-A*02) with human β{sub 2}m and an immunodominant SIV-Gag nonapeptide, GESNLKSLY (GY9), has been crystallized. The crystal diffracts X-rays to 2.7 Å resolution and belongs to space group C2, with unit-cell parameters a = 124.11, b = 110.45, c = 100.06 Å, and contains two molecules in the asymmetric unit. The availability of the structure, which is being solved by molecular replacement, will provide new insights into rhesus macaque MHC I (Mamu-A*02) presenting pathogenic SIV peptides.

  1. Monkey business : the illegal trade in Barbary macaques

    NARCIS (Netherlands)

    van Uhm, D.P.|info:eu-repo/dai/nl/380477025

    2016-01-01

    This article focuses on the organization, modus operandi and trade route of the illegal trade in Barbary macaques. The Barbary macaque is the most seized CITES mammal in the EU, accounting for almost 25% of live mammalrelated seizures. It is estimated that as few as 5,000-6,000 Barbary macaques

  2. Safety study of the Bio-10-SAD Bern strain of the rabies virus on the rhesus macaque monkey species

    Directory of Open Access Journals (Sweden)

    Vladimír Vrzal

    2013-01-01

    Full Text Available Based on a WHO recommendation, residual pathogenicity of the Bio-10-SAD Bern rabies virus strain (component of the Lysvulpen por. ad us. vet. vaccine was tested on rhesus macaque monkeys. Each of the ten monkeys, females, two years old, was administered orally 2 ml × 109 TCID50 of the Bio-10-SAD Bern rabies strain. The animals were monitored for 90 days. Subsequently, the animals were sacrificed and their brains were examined for presence of the vaccination rabies virus by the immunofluorescence and PCR methods. The occurrence of anti-rabies antibodies prior to and following administration of the vaccination rabies virus was also evaluated. No clinical signs of rabies were observed nor did any of the animals die of rabies following application of the virus. No rabies was detected in the study animals by post mortem examination. All of the 10 animals developed anti-rabies antibodies during the 90 days following administration of the rabies virus. It can be concluded, that Bio-10-SAD Bern virus administered at a dose equal to the tenfold maximum dose specified for field uses is safe to monkeys of the rhesus macaque species. This study is the first of its type performed in rhesus macaque monkey species.

  3. Ambiguity aversion in rhesus macaques

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    Benjamin eHayden

    2010-09-01

    Full Text Available People generally prefer risky options, which have fully specified outcome probabilities, to ambiguous options, which have unspecified probabilities. This preference, formalized in economics, is strong enough that people will reliably prefer a risky option to an ambiguous option with a greater expected value. Explanations for ambiguity aversion often invoke uniquely human faculties like language, self-justification, or a desire to avoid public embarrassment. Challenging these ideas, here we demonstrate that a preference for unambiguous options is shared with rhesus macaques. We trained four monkeys to choose between pairs of options that both offered explicitly cued probabilities of large and small juice outcomes. We then introduced occasional trials where one of the options was obscured and examined their resulting preferences; we ran humans in a parallel experiment on a nearly identical task. We found that monkeys reliably preferred risky options to ambiguous ones, even when this bias was costly, closely matching the behavior of humans in the analogous task. Notably, ambiguity aversion varied parametrically with the extent of ambiguity. As expected, ambiguity aversion gradually declined as monkeys learned the underlying probability distribution of rewards. These data indicate that ambiguity aversion reflects fundamental cognitive biases shared with other animals rather than uniquely human factors guiding decisions.

  4. Venezuelan equine encephalitis virus replicon particle vaccine protects nonhuman primates from intramuscular and aerosol challenge with ebolavirus.

    Science.gov (United States)

    Herbert, Andrew S; Kuehne, Ana I; Barth, James F; Ortiz, Ramon A; Nichols, Donald K; Zak, Samantha E; Stonier, Spencer W; Muhammad, Majidat A; Bakken, Russell R; Prugar, Laura I; Olinger, Gene G; Groebner, Jennifer L; Lee, John S; Pratt, William D; Custer, Max; Kamrud, Kurt I; Smith, Jonathan F; Hart, Mary Kate; Dye, John M

    2013-05-01

    There are no vaccines or therapeutics currently approved for the prevention or treatment of ebolavirus infection. Previously, a replicon vaccine based on Venezuelan equine encephalitis virus (VEEV) demonstrated protective efficacy against Marburg virus in nonhuman primates. Here, we report the protective efficacy of Sudan virus (SUDV)- and Ebola virus (EBOV)-specific VEEV replicon particle (VRP) vaccines in nonhuman primates. VRP vaccines were developed to express the glycoprotein (GP) of either SUDV or EBOV. A single intramuscular vaccination of cynomolgus macaques with VRP expressing SUDV GP provided complete protection against intramuscular challenge with SUDV. Vaccination against SUDV and subsequent survival of SUDV challenge did not fully protect cynomolgus macaques against intramuscular EBOV back-challenge. However, a single simultaneous intramuscular vaccination with VRP expressing SUDV GP combined with VRP expressing EBOV GP did provide complete protection against intramuscular challenge with either SUDV or EBOV in cynomolgus macaques. Finally, intramuscular vaccination with VRP expressing SUDV GP completely protected cynomolgus macaques when challenged with aerosolized SUDV, although complete protection against aerosol challenge required two vaccinations with this vaccine.

  5. The most common Chinese rhesus macaque MHC class I molecule shares peptide binding repertoire with the HLA-B7 supertype

    DEFF Research Database (Denmark)

    Solomon, C.; Southwood, S.; Hoof, Ilka

    2010-01-01

    Of the two rhesus macaque subspecies used for AIDS studies, the Simian immunodeficiency virus-infected Indian rhesus macaque (Macaca mulatta) is the most established model of HIV infection, providing both insight into pathogenesis and a system for testing novel vaccines. Despite the Chinese rhesus.......3%) of the sequences identified were novel. From all MHC alleles detected, we prioritized Mamu-A1*02201 for functional characterization based on its higher frequency of expression. Upon the development of MHC/peptide binding assays and definition of its associated motif, we revealed that this allele shares peptide...

  6. Development of a Zika Virus Infection Model in Cynomolgus Macaques

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    Fusataka Koide

    2016-12-01

    Full Text Available Limited availability of Indian rhesus macaques (IRM is a bottleneck to study Zika virus (ZIKV pathogenesis and evaluation of appropriate control measures in non-human primates. To address these issues, we report here the Mauritian cynomolgus macaque (MCM model for ZIKV infection. In brief, six MCMs (seronegative for dengue and ZIKV were subdivided into 3 cohorts with a male and female each and challenged with different doses of Asian PRVABC59 (Puerto Rico or FSS13025 (Cambodia or African (IBH30656 lineage ZIKV isolates. Clinical signs were monitored; and biological fluids (serum, saliva and urine and tissues (testes and brain were assessed for viral load by quantitative RT-PCR and neutralizing antibodies (Nab by 50% Plaque Reduction Neutralization Test (PRNT50 at various times post infection (p.i. PRVABC59 induced viremia detectable up to day 10, with peak viral load at 2 to 3 days p.i. An intermittent viremia spike was observed on day 30 with titers reaching 2.5 ×103 genomes/mL. Moderate viral load was observed in testes, urine and saliva. In contrast, FSS13025 induced viremia lasting only up to 6 days and detectable viral loads in testes but not in urine and saliva. Recurrent viremia was detected but at lower titers compare to PRVABC59. Challenge with either PRVABC59 or FSS13025 resulted in 100% seroconversion; with mean PRNT50 titers ranging from 597 to 5179. IBH30656 failed to establish infection in MCM suggesting that MCM are susceptible to infection with ZIKV isolates of the Asian lineage but not from Africa. Due to the similarity of biphasic viremia and Nab responses between MCM and IRM models, MCM could be a suitable alternative for evaluation of ZIKV vaccine and therapeutic candidates.

  7. Gene targeting in adult rhesus macaque fibroblasts

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    Wolf Don P

    2008-03-01

    Full Text Available Abstract Background Gene targeting in nonhuman primates has the potential to produce critical animal models for translational studies related to human diseases. Successful gene targeting in fibroblasts followed by somatic cell nuclear transfer (SCNT has been achieved in several species of large mammals but not yet in primates. Our goal was to establish the protocols necessary to achieve gene targeting in primary culture of adult rhesus macaque fibroblasts as a first step in creating nonhuman primate models of genetic disease using nuclear transfer technology. Results A primary culture of adult male fibroblasts was transfected with hTERT to overcome senescence and allow long term in vitro manipulations. Successful gene targeting of the HPRT locus in rhesus macaques was achieved by electroporating S-phase synchronized cells with a construct containing a SV40 enhancer. Conclusion The cell lines reported here could be used for the production of null mutant rhesus macaque models of human genetic disease using SCNT technology. In addition, given the close evolutionary relationship and biological similarity between rhesus macaques and humans, the protocols described here may prove useful in the genetic engineering of human somatic cells.

  8. Personality structure and social style in macaques.

    Science.gov (United States)

    Adams, Mark James; Majolo, Bonaventura; Ostner, Julia; Schülke, Oliver; De Marco, Arianna; Thierry, Bernard; Engelhardt, Antje; Widdig, Anja; Gerald, Melissa S; Weiss, Alexander

    2015-08-01

    Why regularities in personality can be described with particular dimensions is a basic question in differential psychology. Nonhuman primates can also be characterized in terms of personality structure. Comparative approaches can help reveal phylogenetic constraints and social and ecological patterns associated with the presence or absence of specific personality dimensions. We sought to determine how different personality structures are related to interspecific variation in social style. Specifically, we examined this question in 6 different species of macaques, because macaque social style is well characterized and can be categorized on a spectrum of despotic (Grade 1) versus tolerant (Grade 4) social styles. We derived personality structures from adjectival ratings of Japanese (Macaca fuscata; Grade 1), Assamese (M. assamensis; Grade 2), Barbary (M. sylvanus; Grade 3), Tonkean (M. tonkeana; Grade 4), and crested (M. nigra; Grade 4) macaques and compared these species with rhesus macaques (M. mulatta; Grade 1) whose personality was previously characterized. Using a nonparametric method, fuzzy set analysis, to identify commonalities in personality dimensions across species, we found that all but 1 species exhibited consistently defined Friendliness and Openness dimensions, but that similarities in personality dimensions capturing aggression and social competence reflect similarities in social styles. These findings suggest that social and phylogenetic relationships contribute to the origin, maintenance, and diversification of personality. (c) 2015 APA, all rights reserved.

  9. Project Lifescape - The Macaques of India

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 6; Issue 9. Project Lifescape - The Macaques of India. Anindya Sinha. Classroom Volume 6 Issue 9 September 2001 pp 94-105. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/006/09/0094-0105 ...

  10. Human exposure to herpesvirus B-seropositive macaques, Bali, Indonesia.

    Science.gov (United States)

    Engel, Gregory A; Jones-Engel, Lisa; Schillaci, Michael A; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

    2002-08-01

    Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a "monkey forest" (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B.

  11. Cytotoxic T-Lymphocyte Escape Does Not Always Explain the Transient Control of Simian Immunodeficiency Virus SIVmac239 Viremia in Adenovirus-Boosted and DNA-Primed Mamu-A*01-Positive Rhesus Macaques

    Science.gov (United States)

    McDermott, Adrian B.; O'Connor, David H.; Fuenger, Sarah; Piaskowski, Shari; Martin, Sarah; Loffredo, John; Reynolds, Matthew; Reed, Jason; Furlott, Jessica; Jacoby, Timothy; Riek, Cara; Dodds, Elizabeth; Krebs, Kendall; Davies, Mary-Ellen; Schleif, William A.; Casimiro, Danilo R.; Shiver, John W.; Watkins, D. I.

    2005-01-01

    Adenovirus 5 (Ad5) vectors show promise as human immunodeficiency virus vaccine candidates. Indian rhesus macaques vaccinated with Ad5-gag controlled simian-human immunodeficiency virus SHIV89.6P viral replication in the absence of Env immunogens that might elicit humoral immunity. Here we immunized 15 macaques using either a homologous Ad5-gag/Ad5-gag (Ad5/Ad5) or a heterologous DNA-gag/Ad5-gag (DNA/Ad5) prime-boost regimen and challenged them with a high dose of simian immunodeficiency virus SIVmac239. Macaques vaccinated with the DNA/Ad5 regimen experienced a brief viral load nadir of less than 10,000 viral copies per ml blood plasma that was not seen in Mamu-A*01-negative DNA/Ad5 vaccinees, Mamu-A*01-positive Ad5/Ad5 vaccinees, or vaccine-naive controls. Interestingly, most of these animals were not durably protected from disease progression when challenged with SIVmac239. To investigate the reasons underlying this short-lived vaccine effect, we investigated breadth of the T-cell response, immunogenetic background, and viral escape from CD8+ lymphocytes that recognize immunodominant T-cell epitopes. We show that these animals do not mount unusually broad cellular immune response, nor do they express unusual major histocompatibility complex class I alleles. Viral recrudescence occurred in four of the five Mamu-A*01-positive vaccinated macaques. However, only a single animal in this group demonstrated viral escape in the immunodominant Gag181-189CM9 response. These results suggest that viral “breakthrough” in vaccinated animals and viral escape are not inextricably linked and underscore the need for additional research into the mechanisms of vaccine failure. PMID:16306626

  12. Protection against H5N1 Highly Pathogenic Avian and Pandemic (H1N1) 2009 Influenza Virus Infection in Cynomolgus Monkeys by an Inactivated H5N1 Whole Particle Vaccine

    Science.gov (United States)

    Nakayama, Misako; Shichinohe, Shintaro; Itoh, Yasushi; Ishigaki, Hirohito; Kitano, Mitsutaka; Arikata, Masahiko; Pham, Van Loi; Ishida, Hideaki; Kitagawa, Naoko; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Ichikawa, Takaya; Tsuchiya, Hideaki; Nakamura, Shinichiro; Le, Quynh Mai; Ito, Mutsumi; Kawaoka, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa

    2013-01-01

    H5N1 highly pathogenic avian influenza virus (HPAIV) infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3), in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1) 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3. PMID:24376571

  13. Protection against H5N1 highly pathogenic avian and pandemic (H1N1 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine.

    Directory of Open Access Journals (Sweden)

    Misako Nakayama

    Full Text Available H5N1 highly pathogenic avian influenza virus (HPAIV infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3, in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3.

  14. Vaccines for HIV | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The development of an effective HIV vaccine has been an ongoing area of research. The high variability in HIV-1 virus strains has represented a major challenge in successful development. Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV. Two major hurdles to overcome are immunodominance and sequence diversity. This vaccine utilizes a strategy for overcoming these two issues by identifying the conserved regions of the virus and exploiting them for use in a targeted therapy. NCI seeks licensees and/or research collaborators to commercialize this technology, which has been validated in macaque models.

  15. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...

  16. Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Rebecca Broeckel

    2017-06-01

    Full Text Available Chikungunya virus (CHIKV is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs, one (4N12 of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12. Because therapeutic administration of SVIR001 in immunocompetent mice significantly reduced viral load in joint tissues, we evaluated its efficacy in a rhesus macaque model of CHIKV infection. Rhesus macaques that were treated after infection with SVIR001 showed rapid elimination of viremia and less severe joint infiltration and disease compared to animals treated with SVIR002, an isotype control mAb. SVIR001 reduced viral burden at the site of infection and at distant sites and also diminished the numbers of activated innate immune cells and levels of pro-inflammatory cytokines and chemokines. SVIR001 therapy; however, did not substantively reduce the induction of CHIKV-specific B or T cell responses. Collectively, these results show promising therapeutic activity of a human anti-CHIKV mAb in rhesus macaques and provide proof-of-principle for its possible use in humans to treat active CHIKV infections.

  17. Heterologous prime-boost regimens with a recombinant chimpanzee adenoviral vector and adjuvanted F4 protein elicit polyfunctional HIV-1-specific T-Cell responses in macaques.

    Science.gov (United States)

    Lorin, Clarisse; Vanloubbeeck, Yannick; Baudart, Sébastien; Ska, Michaël; Bayat, Babak; Brauers, Geoffroy; Clarinval, Géraldine; Donner, Marie-Noëlle; Marchand, Martine; Koutsoukos, Marguerite; Mettens, Pascal; Cohen, Joe; Voss, Gerald

    2015-01-01

    HIV-1-specific CD4+ and CD8+ T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4+ T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8+ T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN ('A'), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 ('P'), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4+ and CD8+ T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4+ T cells. Approximately 50% of AdC7-GRN-induced memory CD8+ T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4+ and CD8+ T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4+ and CD8+ T-cell responses and antibodies in macaques. Besides

  18. Biologically-directed modeling reflects cytolytic clearance of SIV-infected cells in vivo in macaques.

    Directory of Open Access Journals (Sweden)

    W David Wick

    Full Text Available The disappointing outcomes of cellular immune-based vaccines against HIV-1 despite strong evidence for the protective role of CD8⁺ T lymphocytes (CTLs has prompted revisiting the mechanisms of cellular immunity. Prior data from experiments examining the kinetics of Simian Immunodeficiency Virus (SIV clearance in infected macaques with or without in vivo CD8 depletion were interpreted as refuting the concept that CTLs suppress SIV/HIV by direct killing of infected cells. Here we briefly review the biological evidence for CTL cytolytic activity in viral infections, and utilize biologically-directed modeling to assess the possibility of a killing mechanism for the antiviral effect of CTLs, taking into account the generation, proliferation, and survival of activated CD4⁺ and CD8⁺ T lymphocytes, as well as the life cycle of the virus. Our analyses of the published macaque data using these models support a killing mechanism, when one considers T lymphocyte and HIV-1 lifecycles, and factors such as the eclipse period before release of virions by infected cells, an exponential pattern of virion production by infected cells, and a variable lifespan for acutely infected cells. We conclude that for SIV/HIV pathogenesis, CTLs deserve their reputation as being cytolytic.

  19. Measles vaccination of nonhuman primates provides partial protection against infection with canine distemper virus.

    Science.gov (United States)

    de Vries, Rory D; Ludlow, Martin; Verburgh, R Joyce; van Amerongen, Geert; Yüksel, Selma; Nguyen, D Tien; McQuaid, Stephen; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L

    2014-04-01

    Measles virus (MV) is being considered for global eradication, which would likely reduce compliance with MV vaccination. As a result, children will grow up without MV-specific immunity, creating a potential niche for closely related animal morbilliviruses such as canine distemper virus (CDV). Natural CDV infection causing clinical signs has never been reported in humans, but recent outbreaks in captive macaques have shown that CDV can cause disease in primates. We studied the virulence and tropism of recombinant CDV expressing enhanced green fluorescent protein in naive and measles-vaccinated cynomolgus macaques. In naive animals CDV caused viremia and fever and predominantly infected CD150(+) lymphocytes and dendritic cells. Virus was reisolated from the upper and lower respiratory tracts, but infection of epithelial or neuronal cells was not detectable at the time points examined, and the infections were self-limiting. This demonstrates that CDV readily infects nonhuman primates but suggests that additional mutations are necessary to achieve full virulence in nonnatural hosts. Partial protection against CDV was observed in measles-vaccinated macaques, as demonstrated by accelerated control of virus replication and limited shedding from the upper respiratory tract. While neither CDV infection nor MV vaccination induced detectable cross-reactive neutralizing antibodies, MV-specific neutralizing antibody levels of MV-vaccinated macaques were boosted by CDV challenge infection, suggesting that cross-reactive VN epitopes exist. Rapid increases in white blood cell counts in MV-vaccinated macaques following CDV challenge suggested that cross-reactive cellular immune responses were also present. This study demonstrates that zoonotic morbillivirus infections can be controlled by measles vaccination. Throughout history viral zoonoses have had a substantial impact on human health. Given the drive toward global eradication of measles, it is essential to understand the

  20. Identification of Rotavirus VP6-Specific CD4+ T Cell Epitopes in a G1P[8] Human Rotavirus-Infected Rhesus Macaque

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    2008-01-01

    Full Text Available A non-human primate model was used to evaluate its potential for identification of rotavirus viral protein 6 (VP6 CD4+ T cell epitopes. Four juvenile rhesus macaques were inoculated with a mixed inoculum (G1P[8] and G9P[8] of human rotaviruses. Infection accompanied by G1P[8] shedding was achieved in the two macaques that had no rotavirus immunoglobulin A (IgA in plasma. To measure the interferon gamma (IFN-γ and tumor necrosis factor (TNF anti-viral cytokines produced by peripheral CD4+ cells that recognize VP6 epitopes, whole blood cells from one infected macaque were stimulated in vitro with VP6 peptides. Stimulation with peptide pools derived from the simian rotavirus VP6 161–395 region revealed reactivity of CD4+ T cells with the VP6 281–331 domain. A VP6 301–315 region was identified as the epitope responsible for IFN-γ production while a broader VP6 293–327 domain was linked to TNF production. These results suggest that human rotavirus-infected macaques can be used for identification of additional epitopes and domains to address specific questions related to the development of pediatric vaccines.

  1. Grooming reciprocity in male Tibetan macaques.

    Science.gov (United States)

    Xia, Dong-Po; Li, Jin-Hua; Garber, Paul A; Matheson, Megan D; Sun, Bing-Hua; Zhu, Yong

    2013-10-01

    In several primate species, adult males are reported to compete for access to reproductive partners as well as forming affiliative and cohesive social bonds based on the exchange of goods or services. We hypothesized that among a broad set of fitness-maximizing strategies, grooming can be used by individual adult males to enhance social relationships through reciprocity and/or through the interchange of grooming for a different but equivalent good or service. We used focal animal sampling and continuously recorded dyadic grooming and agonistic interactions to test a series of predictions regarding male social interactions in a free-ranging group of Tibetan macaques (Macaca thibetana) at Huangshan, China. During the non-mating season or between males of similar rank throughout the year, grooming effort given was matched by grooming effort received. However, lower ranking males groomed higher ranking males at a greater rate and/or for a longer duration during both the mating and non-mating periods. We found that higher ranking males directed less aggression towards males with whom they formed a frequent grooming partnership, indicating that grooming received was interchanged for increased social tolerance. These data suggest that individual male Tibetan macaques employ alternative social strategies associated with grooming reciprocity or interchange depending on dominance rank and rates of aggression, and highlight the importance of both biological markets and grooming reciprocity as behavioral mechanisms used by resident adult males to form and maintain affiliative social bonds. © 2013 Wiley Periodicals, Inc.

  2. The Cynomolgus Macaque Natural History Model of Pneumonic Tularemia for Predicting Clinical Efficacy Under the Animal Rule

    Science.gov (United States)

    Guina, Tina; Lanning, Lynda L.; Omland, Kristian S.; Williams, Mark S.; Wolfraim, Larry A.; Heyse, Stephen P.; Houchens, Christopher R.; Sanz, Patrick; Hewitt, Judith A.

    2018-01-01

    Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans and a Tier 1 select agent. The natural incidence of pneumonic tularemia worldwide is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCM) in human populations. Development and licensure of tularemia therapeutics and vaccines need to occur under the Food and Drug Administration's (FDA's) Animal Rule under which efficacy studies are conducted in well-characterized animal models that reflect the pathophysiology of human disease. The Tularemia Animal Model Qualification (AMQ) Working Group is seeking qualification of the cynomolgus macaque (Macaca fascicularis) model of pneumonic tularemia under Drug Development Tools Qualification Programs with the FDA based upon the results of studies described in this manuscript. Analysis of data on survival, average time to death, average time to fever onset, average interval between fever and death, and bacteremia; together with summaries of clinical signs, necropsy findings, and histopathology from the animals exposed to aerosolized F. tularensis Schu S4 in five natural history studies and one antibiotic efficacy study form the basis for the proposed cynomolgus macaque model. Results support the conclusion that signs of pneumonic tularemia in cynomolgus macaques exposed to 300–3,000 colony forming units (cfu) aerosolized F. tularensis Schu S4, under the conditions described herein, and human pneumonic tularemia cases are highly similar. Animal age, weight, and sex of animals challenged with 300–3,000 cfu Schu S4 did not impact fever onset in studies described herein. This study summarizes critical parameters and endpoints of a well-characterized cynomolgus macaque model of pneumonic tularemia and demonstrates this model is appropriate for qualification, and for testing efficacy of tularemia therapeutics under Animal Rule. PMID

  3. GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates.

    Directory of Open Access Journals (Sweden)

    Peter T Loudon

    2010-06-01

    Full Text Available The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a world-wide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99 HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun was analyzed in rhesus macaques.Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particle-mediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine.These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skin-delivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract.

  4. Convergent evolution of SIV env after independent inoculation of rhesus macaques with infectious proviral DNA

    International Nuclear Information System (INIS)

    Buckley, Kathleen A.; Li Peilin; Khimani, Anis H.; Hofmann-Lehmann, Regina; Liska, Vladimir; Anderson, Daniel C.; McClure, Harold M.; Ruprecht, Ruth M.

    2003-01-01

    The env gene of three simian immunodeficiency virus (SIV) variants developed convergent mutations during disease progression in six rhesus macaques. The monkeys had been inoculated with supercoiled plasmids encoding infectious proviruses of SIVmac239 (a pathogenic, wild-type strain), SIVΔ3 (the live attenuated vaccine strain derived from SIVmac239), or SIVΔ3+ (a pathogenic progeny virus that had evolved from SIVΔ3). All six monkeys developed immunodeficiency and progressed to fatal disease. Although many divergent mutations arose in env among the different hosts, three regions consistently mutated in all monkeys studied; these similar mutations developed independently even though the animals had received only a single infectious molecular clone rather than standard viral inocula that contain viral quasispecies. Together, these data indicate that the env genes of SIVmac239, SIVΔ3, and SIVΔ3+, in the context of different proviral backbones, evolve similarly in different hosts during disease progression

  5. Genetic characterization of rhesus macaques (Macaca mulatta) in Nepal.

    Science.gov (United States)

    Kyes, Randall C; Jones-Engel, Lisa; Chalise, Mukesh K; Engel, Gregory; Heidrich, John; Grant, Richard; Bajimaya, Shyam S; McDonough, John; Smith, David Glenn; Ferguson, Betsy

    2006-05-01

    Indian-origin rhesus macaques (Macaca mulatta) have long served as an animal model for the study of human disease and behavior. Given the current shortage of Indian-origin rhesus, many researchers have turned to rhesus macaques from China as a substitute. However, a number of studies have identified marked genetic differences between the Chinese and Indian animals. We investigated the genetic characteristics of a third rhesus population, the rhesus macaques of Nepal. Twenty-one rhesus macaques at the Swoyambhu Temple in Kathmandu, Nepal, were compared with more than 300 Indian- and Chinese-origin rhesus macaques. The sequence analyses of two mitochondrial DNA (mtDNA) loci, from the HVS I and 12 S rRNA regions, showed that the Nepali animals were more similar to Indian-origin than to Chinese-origin animals. The distribution of alleles at 24 short tandem repeat (STR) loci distributed across 17 chromosomes also showed greater similarity between the Nepali and Indian-origin animals. Finally, an analysis of seven major histocompatibility complex (MHC) alleles showed that the Nepali animals expressed Class I alleles that are common to Indian-origin animals, including Mamu-A*01. All of these analyses also revealed a low level of genetic diversity within this Nepali rhesus sample. We conclude that the rhesus macaques of Nepal more closely resemble rhesus macaques of Indian origin than those of Chinese origin. As such, the Nepali rhesus may offer an additional resource option for researchers who wish to maintain research protocols with animals that possess key genetic features characteristic of Indian-origin rhesus macaques. 2005 Wiley-Liss, Inc.

  6. Manual lateralization in macaques: handedness, target laterality and task complexity.

    Science.gov (United States)

    Regaiolli, Barbara; Spiezio, Caterina; Vallortigara, Giorgio

    2016-01-01

    Non-human primates represent models to understand the evolution of handedness in humans. Despite several researches have been investigating non-human primates handedness, few studies examined the relationship between target position, hand preference and task complexity. This study aimed at investigating macaque handedness in relation to target laterality and tastiness, as well as task complexity. Seven pig-tailed macaques (Macaca nemestrina) were involved in three different "two alternative choice" tests: one low-level task and two high-level tasks (HLTs). During the first and the third tests macaques could select a preferred food and a non-preferred food, whereas by modifying the design of the second test, macaques were presented with no-difference alternative per trial. Furthermore, a simple-reaching test was administered to assess hand preference in a social context. Macaques showed hand preference at individual level both in simple and complex tasks, but not in the simple-reaching test. Moreover, target position seemed to affect hand preference in retrieving an object in the low-level task, but not in the HLT. Additionally, individual hand preference seemed to be affected from the tastiness of the item to be retrieved. The results suggest that both target laterality and individual motivation might influence hand preference of macaques, especially in simple tasks.

  7. Green revolution vaccines, edible vaccines

    African Journals Online (AJOL)

    Admin

    of development. Food vaccines may also help to suppress autoimmunity disorders such as Type-1. Diabetes. Key words: Edible vaccines, oral vaccines, antigen expression, food vaccines. INTRODUCTION. Vaccination involves the stimulation of the immune system to prepare it for the event of an invasion from a particular ...

  8. Vaccine Safety

    Science.gov (United States)

    ... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...

  9. Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates

    OpenAIRE

    Bolton, Diane L.; Santra, Sampa; Swett, Cindy; Custers, Jerome; Song, Kaimei; Balachandran, Harikrishnan; Kozlowski, Pamela A.; Letvin, Norman; Roederer, Mario; Radošević, Katarina

    2012-01-01

    Licensed live attenuated virus vaccines capable of expressing transgenes from other pathogens have the potential to reduce the number of childhood immunizations by eliciting robust immunity to multiple pathogens simultaneously. Recombinant attenuated measles virus (rMV) derived from the Edmonston Zagreb vaccine strain was engineered to express simian immunodeficiency virus (SIV) Gag protein for the purpose of evaluating the immunogenicity of rMV as a vaccine vector in rhesus macaques. rMV-Gag...

  10. Vicarious Reinforcement In Rhesus Macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Steve W. C. Chang

    2011-03-01

    Full Text Available What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that this reinforcement can motivate them to subsequently deliver or withhold rewards from the other animal. We exploited Pavlovian and instrumental conditioning to associate rewards to self (M1 and/or rewards to another monkey (M2 with visual cues. M1s made more errors in the instrumental trials when cues predicted reward to M2 compared to when cues predicted reward to M1, but made even more errors when cues predicted reward to no one. In subsequent preference tests between pairs of conditioned cues, M1s preferred cues paired with reward to M2 over cues paired with reward to no one. By contrast, M1s preferred cues paired with reward to self over cues paired with reward to both monkeys simultaneously. Rates of attention to M2 strongly predicted the strength and valence of vicarious reinforcement. These patterns of behavior, which were absent in nonsocial control trials, are consistent with vicarious reinforcement based upon sensitivity to observed, or counterfactual, outcomes with respect to another individual. Vicarious reward may play a critical role in shaping cooperation and competition, as well as motivating observational learning and group coordination in rhesus macaques, much as it does in humans. We propose that vicarious reinforcement signals mediate these behaviors via homologous neural circuits involved in reinforcement learning and decision-making.

  11. Vicarious reinforcement in rhesus macaques (macaca mulatta).

    Science.gov (United States)

    Chang, Steve W C; Winecoff, Amy A; Platt, Michael L

    2011-01-01

    What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that this reinforcement can motivate them to subsequently deliver or withhold rewards from the other animal. We exploited Pavlovian and instrumental conditioning to associate rewards to self (M1) and/or rewards to another monkey (M2) with visual cues. M1s made more errors in the instrumental trials when cues predicted reward to M2 compared to when cues predicted reward to M1, but made even more errors when cues predicted reward to no one. In subsequent preference tests between pairs of conditioned cues, M1s preferred cues paired with reward to M2 over cues paired with reward to no one. By contrast, M1s preferred cues paired with reward to self over cues paired with reward to both monkeys simultaneously. Rates of attention to M2 strongly predicted the strength and valence of vicarious reinforcement. These patterns of behavior, which were absent in non-social control trials, are consistent with vicarious reinforcement based upon sensitivity to observed, or counterfactual, outcomes with respect to another individual. Vicarious reward may play a critical role in shaping cooperation and competition, as well as motivating observational learning and group coordination in rhesus macaques, much as it does in humans. We propose that vicarious reinforcement signals mediate these behaviors via homologous neural circuits involved in reinforcement learning and decision-making.

  12. Efficacy of Vesicular Stomatitis Virus-Ebola Virus Postexposure Treatment in Rhesus Macaques Infected With Ebola Virus Makona.

    Science.gov (United States)

    Marzi, Andrea; Hanley, Patrick W; Haddock, Elaine; Martellaro, Cynthia; Kobinger, Gary; Feldmann, Heinz

    2016-10-15

    The Ebola virus (EBOV) epidemic in West Africa increased the focus on vaccine development against this hemorrhagic fever-causing pathogen, and as a consequence human clinical trials for a few selected platforms were accelerated. One of these vaccines is vesicular stomatitis virus (VSV)-EBOV, also known as rVSV-ZEBOV, a fast-acting vaccine against EBOV and so far the only vaccine with reported efficacy against EBOV infections in humans in phase III clinical trials. In this study, we analyzed the potential of VSV-EBOV for postexposure treatment of rhesus macaques infected with EBOV-Makona. We treated groups of animals with 1 dose of VSV-EBOV either in a single injection at 1 or 24 hours after EBOV exposure or with 2 injections, half the dose at each time point; 1 control group received the same dose of the VSV-based Marburg virus vaccine at both time points; another group remained untreated. Although all untreated animals succumbed to EBOV infection, 33%-67% of the animals in each treatment group survived the infection, including the group treated with the VSV-based Marburg virus vaccine. This result suggests that protection from postexposure vaccination may be antigen unspecific and due rather to an early activation of the innate immune system. In conclusion, VSV-EBOV remains a potent and fast-acting prophylactic vaccine but demonstrates only limited efficacy in postexposure treatment. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  13. Ancestry, Plasmodium cynomolgi prevalence and rhesus macaque admixture in cynomolgus macaques (Macaca fascicularis) bred for export in Chinese breeding farms.

    Science.gov (United States)

    Zhang, Xinjun; Meng, Yuhuan; Houghton, Paul; Liu, Mingyu; Kanthaswamy, Sreetharan; Oldt, Robert; Ng, Jillian; Trask, Jessica Satkoski; Huang, Ren; Singh, Balbir; Du, Hongli; Smith, David Glenn

    2017-04-01

    Most cynomolgus macaques (Macaca fascicularis) used in the United States as animal models are imported from Chinese breeding farms without documented ancestry. Cynomolgus macaques with varying rhesus macaque ancestry proportions may exhibit differences, such as susceptibility to malaria, that affect their suitability as a research model. DNA of 400 cynomolgus macaques from 10 Chinese breeding farms was genotyped to characterize their regional origin and rhesus ancestry proportion. A nested PCR assay was used to detect Plasmodium cynomolgi infection in sampled individuals. All populations exhibited high levels of genetic heterogeneity and low levels of inbreeding and genetic subdivision. Almost all individuals exhibited an Indochinese origin and a rhesus ancestry proportion of 5%-48%. The incidence of P. cynomolgi infection in cynomolgus macaques is strongly associated with proportion of rhesus ancestry. The varying amount of rhesus ancestry in cynomolgus macaques underscores the importance of monitoring their genetic similarity in malaria research. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Vesicular stomatitis virus-based vaccines protect nonhuman primates against Bundibugyo ebolavirus.

    Directory of Open Access Journals (Sweden)

    Chad E Mire

    Full Text Available Ebola virus (EBOV causes severe and often fatal hemorrhagic fever in humans and nonhuman primates (NHPs. Currently, there are no licensed vaccines or therapeutics for human use. Recombinant vesicular stomatitis virus (rVSV-based vaccine vectors, which encode an EBOV glycoprotein in place of the VSV glycoprotein, have shown 100% efficacy against homologous Sudan ebolavirus (SEBOV or Zaire ebolavirus (ZEBOV challenge in NHPs. In addition, a single injection of a blend of three rVSV vectors completely protected NHPs against challenge with SEBOV, ZEBOV, the former Côte d'Ivoire ebolavirus, and Marburg virus. However, recent studies suggest that complete protection against the newly discovered Bundibugyo ebolavirus (BEBOV using several different heterologous filovirus vaccines is more difficult and presents a new challenge. As BEBOV caused nearly 50% mortality in a recent outbreak any filovirus vaccine advanced for human use must be able to protect against this new species. Here, we evaluated several different strategies against BEBOV using rVSV-based vaccines. Groups of cynomolgus macaques were vaccinated with a single injection of a homologous BEBOV vaccine, a single injection of a blended heterologous vaccine (SEBOV/ZEBOV, or a prime-boost using heterologous SEBOV and ZEBOV vectors. Animals were challenged with BEBOV 29-36 days after initial vaccination. Macaques vaccinated with the homologous BEBOV vaccine or the prime-boost showed no overt signs of illness and survived challenge. In contrast, animals vaccinated with the heterologous blended vaccine and unvaccinated control animals developed severe clinical symptoms consistent with BEBOV infection with 2 of 3 animals in each group succumbing. These data show that complete protection against BEBOV will likely require incorporation of BEBOV glycoprotein into the vaccine or employment of a prime-boost regimen. Fortunately, our results demonstrate that heterologous rVSV-based filovirus vaccine

  15. Vaccines.gov

    Science.gov (United States)

    ... Vaccine Safety Vaccines Work Vaccine Types Vaccine Ingredients Vaccines by Disease Chickenpox ... Typhoid Fever Whooping Cough (Pertussis) Yellow Fever Who and When Infants, Children, and Teens ...

  16. Immunogenicity in pig-tailed macaques of poliovirus replicons expressing HIV-1 and SIV antigens and protection against SHIV-89.6P disease

    International Nuclear Information System (INIS)

    Fultz, Patricia N.; Stallworth, Jackie; Porter, Donna; Novak, Miroslav; Anderson, Marie J.; Morrow, Casey D.

    2003-01-01

    In the search for an effective vaccine against the human immunodeficiency virus (HIV), novel ways to deliver viral antigens are being evaluated. One such approach is the use of nonreplicating viral vectors encoding HIV and/or SIV genes that are expressed after infection of host cells. Nonreplicating poliovirus vectors, termed replicons, that expressed HIV-1/HXB2 and SIVmac239 gag and various HIV-1 env genes from different clades were tested for immunogenicity and protective efficacy against intravenous challenge of pig-tailed macaques with SHIV-89.6P. To maximize both cellular and humoral immune responses, a prime-boost regimen was used. Initially, macaques were immunized four times over 35 weeks by either the intranasal and intrarectal or the intramuscular (im) route with mixtures of poliovirus replicons expressing HIV-1 gag and multiple env genes. Immunization with replicons alone induced both serum antibodies and lymphocyte proliferative responses. After boosting with purified Env protein, neutralizing antibodies to SHIV-89.6P were induced in four of five immunized animals. In a second experiment, four macaques were immunized im three times over 27 weeks with replicons expressing the SIVmac239 gag and HIV-1/HXB2 env genes. All immunized animals were then boosted twice with purified HIV-1-89.6 rgp140-Env and SIVmac239 p55-Gag proteins. Four control animals received only the two protein inoculations. Immunized and control animals were then challenged intravenously with the pathogenic SHIV-89.6P. After challenge the animals were monitored for virus isolation from peripheral blood mononuclear cells and plasma viremia and for changes in virus-specific antibody titers. Naieve pig-tailed macaques experienced rapid loss of CD4 + T cells and died between 38 and 62 weeks after infection. In contrast, macaques immunized with replicons and proteins rapidly cleared plasma virus and did not experience sustained loss of CD4 + lymphocytes. Furthermore, two of the four macaques

  17. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver [Robert Koch-Institut, Berlin (Germany); Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D. [Paul-Ehrlich-Institut, Langen (Germany); Bannert, Norbert; Kurth, Reinhard [Robert Koch-Institut, Berlin (Germany); Norley, Stephen, E-mail: NorleyS@rki.de [Robert Koch-Institut, Berlin (Germany)

    2016-02-15

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  18. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    International Nuclear Information System (INIS)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver; Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D.; Bannert, Norbert; Kurth, Reinhard; Norley, Stephen

    2016-01-01

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  19. A Characterization of Aerosolized Sudan Virus Infection in African Green Monkeys, Cynomolgus Macaques, and Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Donald K. Nichols

    2012-10-01

    Full Text Available Filoviruses are members of the genera Ebolavirus, Marburgvirus, and “Cuevavirus”. Because they cause human disease with high lethality and could potentially be used as a bioweapon, these viruses are classified as CDC Category A Bioterrorism Agents. Filoviruses are relatively stable in aerosols, retain virulence after lyophilization, and can be present on contaminated surfaces for extended periods of time. This study explores the characteristics of aerosolized Sudan virus (SUDV Boniface in non-human primates (NHP belonging to three different species. Groups of cynomolgus macaques (cyno, rhesus macaques (rhesus, and African green monkeys (AGM were challenged with target doses of 50 or 500 plaque-forming units (pfu of aerosolized SUDV. Exposure to either viral dose resulted in increased body temperatures in all three NHP species beginning on days 4–5 post-exposure. Other clinical findings for all three NHP species included leukocytosis, thrombocytopenia, anorexia, dehydration, and lymphadenopathy. Disease in all of the NHPs was severe beginning on day 6 post-exposure, and all animals except one surviving rhesus macaque were euthanized by day 14. Serum alanine transaminase (ALT and aspartate transaminase (AST concentrations were elevated during the course of disease in all three species; however, AGMs had significantly higher ALT and AST concentrations than cynos and rhesus. While all three species had detectable viral load by days 3-4 post exposure, Rhesus had lower average peak viral load than cynos or AGMs. Overall, the results indicate that the disease course after exposure to aerosolized SUDV is similar for all three species of NHP.

  20. Risk and Resilience: Early Manipulation of Macaque Social Experience and Persistent Behavioral and Neurophysiological Outcomes

    Science.gov (United States)

    Stevens, Hanna E.; Leckman, James F.; Coplan, Jeremy D.; Suomi, Stephen J.

    2009-01-01

    A literature review on macaque monkeys finds that peer rearing of young macaques and rearing of young macaques by mothers that are undergoing variable foraging conditions result in emotional and neurophysiological disturbance. Certain genotypes contribute to resilience to this disturbance. The findings have implications to child mental health and…

  1. Respiratory and oral vaccination improves protection conferred by the live vaccine strain against pneumonic tularemia in the rabbit model.

    Science.gov (United States)

    Stinson, Elizabeth; Smith, Le'Kneitah P; Cole, Kelly Stefano; Barry, Eileen M; Reed, Douglas S

    2016-10-01

    Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Rotavirus vaccines

    Directory of Open Access Journals (Sweden)

    Kang G

    2006-01-01

    Full Text Available Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licenced vaccines are either animal-human reassortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies.

  3. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel.

    Directory of Open Access Journals (Sweden)

    Martin Cranage

    2008-08-01

    Full Text Available The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT inhibitor tenofovir (PMPA, 9-[(R-2-(phosphonomethoxy propyl] adenine monohydrate, a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV in a well-established and standardised macaque model.A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50 of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC, quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA load by sensitive quantitative competitive (qc RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from infection (n = 6 or had

  4. Rotational displacement skills in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Hughes, Kelly D; Santos, Laurie R

    2012-11-01

    Rotational displacement tasks, in which participants must track an object at a hiding location within an array while the array rotates, exhibit a puzzling developmental pattern in humans. Human children take an unusually long time to master this task and tend to solve rotational problems through the use of nongeometric features or landmarks as opposed to other kinds of spatial cues. We investigated whether these developmental characteristics are unique to humans by testing rotational displacement skills in a monkey species, the rhesus macaque (Macaca mulatta), using a looking-time method. Monkeys first saw food hidden in two differently colored boxes within an array. The array was then rotated 180° and the boxes reopened to reveal the food in an expected or unexpected location. Our first two experiments explored the developmental time-course of performance on this rotational displacement task. We found that adult macaques looked longer at the unexpected event, but such performance was not mirrored in younger-aged macaques. In a third study, we systematically varied featural information and visible access to the array to investigate which strategies adult macaques used in solving rotational displacements. Our results show that adult macaques need both sets of information to solve the task. Taken together, these results suggest both similarities and differences in mechanisms by which human and nonhuman primates develop this spatial skill.

  5. Analysis of carboxylesterase 2 transcript variants in cynomolgus macaque liver.

    Science.gov (United States)

    Uno, Yasuhiro; Igawa, Yoshiyuki; Tanaka, Maori; Ohura, Kayoko; Hosokawa, Masakiyo; Imai, Teruko

    2018-04-27

    Carboxylesterase (CES) is important for the detoxification of a wide range of drugs and xenobiotics. In this study, the hepatic level of CES2 mRNA was examined in cynomolgus macaques used widely in preclinical studies for drug metabolism. Three CES2 mRNAs were present in cynomolgus macaque liver. The mRNA level was highest for cynomolgus CES2A (formerly CES2v3), much lower for cynomolgus CES2B (formerly CES2v1) and extremely low for cynomolgus CES2C (formerly CES2v2). Most various transcript variants produced from cynomolgus CES2B gene did not contain a complete coding region. Thus, CES2A is the major CES2 enzyme in cynomolgus liver. A new transcript variant of CES2A, CES2Av2, was identified. CES2Av2 contained exon 3 region different from wild-type (CES2Av1). In cynomolgus macaques expressing only CES2Av2 transcript, CES2A contained the sequence of CES2B in exon 3 and vicinity, probably due to gene conversion. On genotyping, this CES2Av2 allele was prevalent in Indochinese cynomolgus macaques, but not in Indonesian cynomolgus or rhesus macaques. CES2Av2 recombinant protein showed similar activity to CES2Av1 protein for several substrates. It is concluded that CES2A is the major cynomolgus hepatic CES2, and new transcript variant, CES2Av2, has similar functions to CES2Av1.

  6. Hepatitis Vaccines

    OpenAIRE

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...

  7. Immunization of rhesus macaques with Echinococcus multilocularis recombinant 14-3-3 antigen leads to specific antibody response.

    Science.gov (United States)

    Lampe, Karen; Gottstein, B; Becker, T; Stahl-Hennig, C; Kaup, F-J; Mätz-Rensing, K

    2017-01-01

    E. multilocularis (Em) is the etiologic agent of alveolar echinococcosis (AE), a severe and potentially fatal disease, primarily affecting the liver of and occurring in aberrant intermediate hosts, e.g., humans and non-human primates. Due to increasing numbers of spontaneous cases of AE in the Old World monkey colonies of the German Primate Center, the question arose as to whether vaccination of non-human primates may represent a useful prophylactic approach. In this pilot study, the recombinant antigen Em14-3-3, which has provided a 97 % protection against E. multilocularis challenge infection in rodent models, was used for the first time to immunize rhesus macaques. In order to increase immunogenicity, the antigen was formulated with different adjuvants including Quil A®, aluminum hydroxide (alum), and muramyl dipeptide (MDP). Also, different vaccination regimens were tested. All vaccinated animals developed antigen-specific antibodies. While Quil A® induced a local adverse reaction, alum proved to be the most potent adjuvant in terms of induced antibody levels, longevity as well as tolerability. In conclusion, our pilot study demonstrated that recombinant Em14-3-3 is safe and immunogenic in rhesus monkeys. As a next step, efficacy of the vaccination remains to be explored.

  8. Inactivated yellow fever 17D vaccine: development and nonclinical safety, immunogenicity and protective activity.

    Science.gov (United States)

    Monath, Thomas P; Lee, Cynthia K; Julander, Justin G; Brown, Alicja; Beasley, David W; Watts, Douglas M; Hayman, Edward; Guertin, Patrick; Makowiecki, Joseph; Crowell, Joseph; Levesque, Philip; Bowick, Gavin C; Morin, Merribeth; Fowler, Elizabeth; Trent, Dennis W

    2010-05-14

    In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age 60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with beta-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX [geometric mean titer (GMT) 20,480 vs. 1940, respectively (Pvaccine or a single dose of YF-VAX were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Rotavirus vaccines

    Science.gov (United States)

    Yen, Catherine; Tate, Jacqueline E; Hyde, Terri B; Cortese, Margaret M; Lopman, Benjamin A; Jiang, Baoming; Glass, Roger I; Parashar, Umesh D

    2014-01-01

    Rotavirus is the leading cause of severe diarrhea among children rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction. PMID:24755452

  10. Cynomolgus macaque as an animal model for severe acute respiratory syndrome.

    Directory of Open Access Journals (Sweden)

    James V Lawler

    2006-05-01

    Full Text Available The emergence of severe acute respiratory syndrome (SARS in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs infected with SARS-CoV.In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.

  11. Priming-boosting vaccination with recombinant Mycobacterium bovis bacillus Calmette-Guérin and a nonreplicating vaccinia virus recombinant leads to long-lasting and effective immunity.

    Science.gov (United States)

    Ami, Yasushi; Izumi, Yasuyuki; Matsuo, Kazuhiro; Someya, Kenji; Kanekiyo, Masaru; Horibata, Shigeo; Yoshino, Naoto; Sakai, Koji; Shinohara, Katsuaki; Matsumoto, Sohkichi; Yamada, Takeshi; Yamazaki, Shudo; Yamamoto, Naoki; Honda, Mitsuo

    2005-10-01

    Virus-specific T-cell responses can limit immunodeficiency virus type 1 (HIV-1) transmission and prevent disease progression and so could serve as the basis for an affordable, safe, and effective vaccine in humans. To assess their potential for a vaccine, we used Mycobacterium bovis bacillus Calmette-Guérin (BCG)-Tokyo and a replication-deficient vaccinia virus strain (DIs) as vectors to express full-length gag from simian immunodeficiency viruses (SIVs) (rBCG-SIVgag and rDIsSIVgag). Cynomolgus macaques were vaccinated with either rBCG-SIVgag dermally as a single modality or in combination with rDIsSIVgag intravenously. When cynomologus macaques were primed with rBCG-SIVgag and then boosted with rDIsSIVgag, high levels of gamma interferon (IFN-gamma) spot-forming cells specific for SIV Gag were induced. This combination regimen elicited effective protective immunity against mucosal challenge with pathogenic simian-human immunodeficiency virus for the 1 year the macaques were under observation. Antigen-specific intracellular IFN-gamma activity was similarly induced in each of the macaques with the priming-boosting regimen. Other groups receiving the opposite combination or the single-modality vaccines were not effectively protected. These results suggest that a recombinant M. bovis BCG-based vector may have potential as an HIV/AIDS vaccine when administered in combination with a replication-deficient vaccinia virus DIs vector in a priming-boosting strategy.

  12. Vaccine Hesitancy.

    Science.gov (United States)

    Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  13. Human-wildlife conflict: proximate predictors of aggression between humans and rhesus macaques in India.

    Science.gov (United States)

    Beisner, Brianne A; Heagerty, Allison; Seil, Shannon K; Balasubramaniam, Krishna N; Atwill, Edward R; Gupta, Brij K; Tyagi, Praveen C; Chauhan, Netrapal P S; Bonal, B S; Sinha, P R; McCowan, Brenda

    2015-02-01

    Macaques live in close contact with humans across South and Southeast Asia, and direct interaction is frequent. Aggressive contact is a concern in many locations, particularly among populations of rhesus and longtail macaques that co-inhabit urbanized cities and towns with humans. We investigated the proximate factors influencing the occurrence of macaque aggression toward humans as well as human aggression toward macaques to determine the extent to which human behavior elicits macaque aggression and vice versa. We conducted a 3-month study of four free-ranging populations of rhesus macaques in Dehradun, India from October-December 2012, using event sampling to record all instances of human-macaque interaction (N = 3120). Our results show that while human aggression was predicted by the potential for economic losses or damage, macaque aggression was influenced by aggressive or intimidating behavior by humans as well as recent rates of conspecific aggression. Further, adult female macaques participated in aggression more frequently than expected, whereas adult and subadult males participated as frequently as expected. Our analyses demonstrate that neither human nor macaque aggression is unprovoked. Rather, both humans and macaques are responding to one another's behavior. Mitigation of human-primate conflict, and indeed other types of human-wildlife conflict in such coupled systems, will require a holistic investigation of the ways in which each participant is responding to, and consequently altering, the behavior of the other. © 2015 Wiley Periodicals, Inc.

  14. Pathology of experimental Machupo virus infection, Chicava strain, in cynomolgus macaques (Macaca fascicularis) by intramuscular and aerosol exposure.

    Science.gov (United States)

    Bell, T M; Shaia, C I; Bunton, T E; Robinson, C G; Wilkinson, E R; Hensley, L E; Cashman, K A

    2015-01-01

    Machupo virus, the causative agent of Bolivian hemorrhagic fever (BHF), is a highly lethal viral hemorrhagic fever of which little is known and for which no Food and Drug Administration-approved vaccines or therapeutics are available. This study evaluated the cynomolgus macaque as an animal model using the Machupo virus, Chicava strain, via intramuscular and aerosol challenge. The incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial skin rash. These were often followed by neurologic signs and death within an average of 18 days. Complete blood counts revealed leukopenia as well as marked thrombocytopenia. Serum chemistry values identified a decrease in total protein, marked increases in alanine aminotransferase and aspartate aminotransferase, and moderate increases in alkaline phosphatase. Gross pathology findings included a macular rash extending across the axillary and inguinal regions beginning at approximately 10 days postexposure as well as enlarged lymph nodes and spleen, enlarged and friable liver, and sporadic hemorrhages along the gastrointestinal mucosa and serosa. Histologic lesions consisted of foci of degeneration and necrosis/apoptosis in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, stomach, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system (nonsuppurative encephalitis) was histologically apparent approximately 16 days postexposure and was generally progressive. This study provides insight into the course of Machupo virus infection in cynomolgus macaques and supports the usefulness of cynomolgus macaques as a viable model of human Machupo virus infection. © The Author(s) 2014.

  15. Mimetic Muscles in a Despotic Macaque (Macaca mulatta) Differ from Those in a Closely Related Tolerant Macaque (M. nigra).

    Science.gov (United States)

    Burrows, Anne M; Waller, Bridget M; Micheletta, Jérôme

    2016-10-01

    Facial displays (or expressions) are a primary means of visual communication among conspecifics in many mammalian orders. Macaques are an ideal model among primates for investigating the co-evolution of facial musculature, facial displays, and social group size/behavior under the umbrella of "ecomorphology". While all macaque species share some social behaviors, dietary, and ecological parameters, they display a range of social dominance styles from despotic to tolerant. A previous study found a larger repertoire of facial displays in tolerant macaque species relative to despotic species. The present study was designed to further explore this finding by comparing the gross morphological features of mimetic muscles between the Sulawesi macaque (Macaca nigra), a tolerant species, and the rhesus macaque (M. mulatta), a despotic species. Five adult M. nigra heads were dissected and mimetic musculature was compared to those from M. mulatta. Results showed that there was general similarity in muscle presence/absence between the species as well as muscle form except for musculature around the external ear. M. mulatta had more musculature around the external ear than M. nigra. In addition, M. nigra lacked a zygomaticus minor while M. mulatta is reported to have one. These morphological differences match behavioral observations documenting a limited range of ear movements used by M. nigra during facial displays. Future studies focusing on a wider phylogenetic range of macaques with varying dominance styles may further elucidate the roles of phylogeny, ecology, and social variables in the evolution of mimetic muscles within Macaca Anat Rec, 299:1317-1324, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Detection thresholds of macaque otolith afferents.

    Science.gov (United States)

    Yu, Xiong-Jie; Dickman, J David; Angelaki, Dora E

    2012-06-13

    The vestibular system is our sixth sense and is important for spatial perception functions, yet the sensory detection and discrimination properties of vestibular neurons remain relatively unexplored. Here we have used signal detection theory to measure detection thresholds of otolith afferents using 1 Hz linear accelerations delivered along three cardinal axes. Direction detection thresholds were measured by comparing mean firing rates centered on response peak and trough (full-cycle thresholds) or by comparing peak/trough firing rates with spontaneous activity (half-cycle thresholds). Thresholds were similar for utricular and saccular afferents, as well as for lateral, fore/aft, and vertical motion directions. When computed along the preferred direction, full-cycle direction detection thresholds were 7.54 and 3.01 cm/s(2) for regular and irregular firing otolith afferents, respectively. Half-cycle thresholds were approximately double, with excitatory thresholds being half as large as inhibitory thresholds. The variability in threshold among afferents was directly related to neuronal gain and did not depend on spike count variance. The exact threshold values depended on both the time window used for spike count analysis and the filtering method used to calculate mean firing rate, although differences between regular and irregular afferent thresholds were independent of analysis parameters. The fact that minimum thresholds measured in macaque otolith afferents are of the same order of magnitude as human behavioral thresholds suggests that the vestibular periphery might determine the limit on our ability to detect or discriminate small differences in head movement, with little noise added during downstream processing.

  17. Cholinergic control of visual categorisation in macaques

    Directory of Open Access Journals (Sweden)

    Nikolaos C. Aggelopoulos

    2011-11-01

    Full Text Available Acetylcholine (ACh is a neurotransmitter acting via muscarinic and nicotinic receptors that is implicated in several cognitive functions and impairments, such as Alzheimer’s disease. It is believed to especially affect the acquisition of new information, which is particularly important when behaviour needs to be adapted to new situations and to novel sensory events. Categorisation, the process of assigning stimuli to a category, is a cognitive function that also involves information acquisition. The role of ACh on categorisation has not been previously studied. We have examined the effects of scopolamine, an antagonist of muscarinic ACh receptors, on visual categorisation in macaque monkeys using familiar and novel stimuli. When the peripheral effects of scopolamine on the parasympathetic nervous system were controlled for, categorisation performance was disrupted following systemic injections of scopolamine. This impairment was observed only when the stimuli that needed to be categorised had not been seen before. In other words, the monkeys were not impaired by the central action of scopolamine in categorising a set of familiar stimuli (stimuli which they had categorised successfully in previous sessions. Categorisation performance also deteriorated as the stimulus became less salient by an increase in the level of visual noise. However, scopolamine did not cause additional performance disruptions for difficult categorisation judgements at lower coherence levels. Scopolamine, therefore, specifically affects the assignment of new exemplars to established cognitive categories, presumably by impairing the processing of novel information. Since we did not find an effect of scopolamine in the categorisation of familiar stimuli, scopolamine had no significant central action on other cognitive functions such as perception, attention, memory or executive control within the context of our categorisation task.

  18. Differential sequence diversity at merozoite surface protein-1 locus of Plasmodium knowlesi from humans and macaques in Thailand.

    Science.gov (United States)

    Putaporntip, Chaturong; Thongaree, Siriporn; Jongwutiwes, Somchai

    2013-08-01

    To determine the genetic diversity and potential transmission routes of Plasmodium knowlesi, we analyzed the complete nucleotide sequence of the gene encoding the merozoite surface protein-1 of this simian malaria (Pkmsp-1), an asexual blood-stage vaccine candidate, from naturally infected humans and macaques in Thailand. Analysis of Pkmsp-1 sequences from humans (n=12) and monkeys (n=12) reveals five conserved and four variable domains. Most nucleotide substitutions in conserved domains were dimorphic whereas three of four variable domains contained complex repeats with extensive sequence and size variation. Besides purifying selection in conserved domains, evidence of intragenic recombination scattering across Pkmsp-1 was detected. The number of haplotypes, haplotype diversity, nucleotide diversity and recombination sites of human-derived sequences exceeded that of monkey-derived sequences. Phylogenetic networks based on concatenated conserved sequences of Pkmsp-1 displayed a character pattern that could have arisen from sampling process or the presence of two independent routes of P. knowlesi transmission, i.e. from macaques to human and from human to humans in Thailand. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Control of viremia and prevention of AIDS following immunotherapy of SIV-infected macaques with peptide-pulsed blood.

    Directory of Open Access Journals (Sweden)

    Robert De Rose

    2008-05-01

    Full Text Available Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIV(mac251 replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably approximately 10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans.

  20. Low dose rectal inoculation of rhesus macaques by SIV smE660 or SIVmac251 recapitulates

    Energy Technology Data Exchange (ETDEWEB)

    Hraber, Peter [Los Alamos National Laboratory; Giorgi, Elena E [Los Alamos National Laboratory; Keele, Brandon [UNIV OF ALABAMA; Li, Hui [UNIV OF ALABAMA; Learn, Gerald [UNIV OF ALABAMA

    2008-01-01

    We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques. Animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV-1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA 1--5 wk after infection. i.r. inoculation was followed by productive infection by one or a few viruses (median 1; range 1--5) that diversified randomly with near starlike phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or a few nucleotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder viruses. i.v. infection was >2,000-fold more efficient than i.r. infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV-macaque mucosal infection model for HIV-1 vaccine and microbicide research.

  1. DHEC: Vaccinations

    Science.gov (United States)

    Data, Maps - SC Public Health Diseases and Conditions Flu Tuberculosis STD/HIV and Viral Hepatitis Zika Illnesses E. coli Listeriosis Salmonella Hepatitis A Shellfish Monitoring and Regulation Certified Shippers Vaccines Teen and Preteen Vaccines Vaccines Needed for School Admission Related Topics Perinatal Hepatitis

  2. Stepping toward a Macaque Model of HIV-1 Induced AIDS

    Directory of Open Access Journals (Sweden)

    Jason T. Kimata

    2014-09-01

    Full Text Available HIV-1 exhibits a narrow host range, hindering the development of a robust animal model of pathogenesis. Past studies have demonstrated that the restricted host range of HIV-1 may be largely due to the inability of the virus to antagonize and evade effector molecules of the interferon response in other species. They have also guided the engineering of HIV-1 clones that can replicate in CD4 T-cells of Asian macaque species. However, while replication of these viruses in macaque hosts is persistent, it has been limited and without progression to AIDS. In a new study, Hatziioannou et al., demonstrate for the first time that adapted macaque-tropic HIV-1 can persistently replicate at high levels in pigtailed macaques (Macaca nemestrina, but only if CD8 T-cells are depleted at the time of inoculation. The infection causes rapid disease and recapitulates several aspects of AIDS in humans. Additionally, the virus undergoes genetic changes to further escape innate immunity in association with disease progression. Here, the importance of these findings is discussed, as they relate to pathogenesis and model development.

  3. Evolutionary and biomedical insights from the rhesus macaque genome

    DEFF Research Database (Denmark)

    Gibbs, Richard A; Rogers, Jeffrey; Katze, Michael G

    2007-01-01

    The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied...

  4. Reconciliation and relationship quality in Assamese macaques (Macaca assamensis)

    NARCIS (Netherlands)

    Cooper, M.A.; Bernstein, I.S.; Hemelrijk, C.K.

    A consistent conclusion in reconciliation research is that animals that reconcile are likely to have strong social bonds. This has led to the hypothesis that reconciliation occurs most often between valuable social partners. We tested this hypothesis in a group of Assamese macaques (Macaca

  5. Molecular characterization and polymorphisms of butyrylcholinesterase in cynomolgus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Uehara, Shotaro; Mahadhi, Hassan M D; Ohura, Kayoko; Hosokawa, Masakiyo; Imai, Teruko

    2018-06-01

    Butyrylcholinesterase (BChE), an enzyme essential for drug metabolism, has been investigated as antidotes against organophosphorus nerve agents, and the efficacy and safety have been studied in cynomolgus macaques. BChE polymorphisms partly account for variable BChE activities among individuals in humans, but have not been investigated in cynomolgus macaques. Molecular characterization was carried out by analyzing primary sequence, gene, tissue expression, and genetic variants. In cynomolgus and human BChE, phylogenetically closely related, amino acid residues important for enzyme function were conserved, and gene and genomic structure were similar. Cynomolgus BChE mRNA was most abundantly expressed in liver among the 10 tissue types analyzed. Re-sequencing found 26 non-synonymous genetic variants in 121 cynomolgus and 23 rhesus macaques, indicating that macaque BChE is polymorphic, although none of these variants corresponded to the null or defective alleles of human BChE. These results suggest molecular similarities of cynomolgus and human BChE. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Expression of cytochrome P450 regulators in cynomolgus macaque.

    Science.gov (United States)

    Uno, Yasuhiro; Yamazaki, Hiroshi

    2017-09-11

    1. Cytochrome P450 (P450) regulators including nuclear receptors and transcription factors have not been fully investigated in cynomolgus macaques, an important species used in drug metabolism studies. In this study, we analyzed 17 P450 regulators by sequence and phylogenetic analysis, and tissue expression. 2. Gene and genome structures of 17 P450 regulators were similar to the human orthologs, and the deduced amino acid sequences showed high sequence identities (92-95%) and more closely clustered in a phylogenetic tree, with the human orthologs. 3. Many of the P450 regulator mRNAs were preferentially expressed in the liver, kidney, and/or jejunum. Among the P450 regulator mRNAs, PXR was most abundant in the liver and jejunum, and HNF4α in the kidney. In the liver, the expression of most P450 regulator mRNAs did not show significant differential expression (>2.5-fold) between cynomolgus macaques bred in Cambodia, China, and Indonesia, or rhesus macaques. 4. By correlation analysis, most of the P450 regulators were significantly (p < 0.05) correlated to other P450 regulators, and many of them were also significantly (p < 0.05) correlated with P450s. 5. These results suggest that 17 P450 regulators of cynomolgus macaques had similar molecular characteristics to the human orthologs.

  7. Occipital White Matter Tracts in Human and Macaque.

    Science.gov (United States)

    Takemura, Hiromasa; Pestilli, Franco; Weiner, Kevin S; Keliris, Georgios A; Landi, Sofia M; Sliwa, Julia; Ye, Frank Q; Barnett, Michael A; Leopold, David A; Freiwald, Winrich A; Logothetis, Nikos K; Wandell, Brian A

    2017-06-01

    We compare several major white-matter tracts in human and macaque occipital lobe using diffusion magnetic resonance imaging. The comparison suggests similarities but also significant differences in the tracts. There are several apparently homologous tracts in the 2 species, including the vertical occipital fasciculus (VOF), optic radiation, forceps major, and inferior longitudinal fasciculus (ILF). There is one large human tract, the inferior fronto-occipital fasciculus, with no corresponding fasciculus in macaque. We could identify the macaque VOF (mVOF), which has been little studied. Its position is consistent with classical invasive anatomical studies by Wernicke. VOF homology is supported by similarity of the endpoints in V3A and ventral V4 across species. The mVOF fibers intertwine with the dorsal segment of the ILF, but the human VOF appears to be lateral to the ILF. These similarities and differences between the occipital lobe tracts will be useful in establishing which circuitry in the macaque can serve as an accurate model for human visual cortex. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Sequence of pathogenic events in cynomolgus macaques infected with aerosolized monkeypox virus.

    Science.gov (United States)

    Tree, J A; Hall, G; Pearson, G; Rayner, E; Graham, V A; Steeds, K; Bewley, K R; Hatch, G J; Dennis, M; Taylor, I; Roberts, A D; Funnell, S G P; Vipond, J

    2015-04-01

    To evaluate new vaccines when human efficacy studies are not possible, the FDA's "Animal Rule" requires well-characterized models of infection. Thus, in the present study, the early pathogenic events of monkeypox infection in nonhuman primates, a surrogate for variola virus infection, were characterized. Cynomolgus macaques were exposed to aerosolized monkeypox virus (10(5) PFU). Clinical observations, viral loads, immune responses, and pathological changes were examined on days 2, 4, 6, 8, 10, and 12 postchallenge. Viral DNA (vDNA) was detected in the lungs on day 2 postchallenge, and viral antigen was detected, by immunostaining, in the epithelium of bronchi, bronchioles, and alveolar walls. Lesions comprised rare foci of dysplastic and sloughed cells in respiratory bronchioles. By day 4, vDNA was detected in the throat, tonsil, and spleen, and monkeypox antigen was detected in the lung, hilar and submandibular lymph nodes, spleen, and colon. Lung lesions comprised focal epithelial necrosis and inflammation. Body temperature peaked on day 6, pox lesions appeared on the skin, and lesions, with positive immunostaining, were present in the lung, tonsil, spleen, lymph nodes, and colon. By day 8, vDNA was present in 9/13 tissues. Blood concentrations of interleukin 1ra (IL-1ra), IL-6, and gamma interferon (IFN-γ) increased markedly. By day 10, circulating IgG antibody concentrations increased, and on day 12, animals showed early signs of recovery. These results define early events occurring in an inhalational macaque monkeypox infection model, supporting its use as a surrogate model for human smallpox. Bioterrorism poses a major threat to public health, as the deliberate release of infectious agents, such smallpox or a related virus, monkeypox, would have catastrophic consequences. The development and testing of new medical countermeasures, e.g., vaccines, are thus priorities; however, tests for efficacy in humans cannot be performed because it would be unethical and

  9. Immunogenicity of NYVAC Prime-Protein Boost Human Immunodeficiency Virus Type 1 Envelope Vaccination and Simian-Human Immunodeficiency Virus Challenge of Nonhuman Primates.

    Science.gov (United States)

    Saunders, Kevin O; Santra, Sampa; Parks, Robert; Yates, Nicole L; Sutherland, Laura L; Scearce, Richard M; Balachandran, Harikrishnan; Bradley, Todd; Goodman, Derrick; Eaton, Amanda; Stanfield-Oakley, Sherry A; Tartaglia, James; Phogat, Sanjay; Pantaleo, Giuseppe; Esteban, Mariano; Gomez, Carmen E; Perdiguero, Beatriz; Jacobs, Bertram; Kibler, Karen; Korber, Bette; Montefiori, David C; Ferrari, Guido; Vandergrift, Nathan; Liao, Hua-Xin; Tomaras, Georgia D; Haynes, Barton F

    2018-04-15

    A preventive human immunodeficiency virus type 1 (HIV-1) vaccine is an essential part of the strategy to eradicate AIDS. A critical question is whether antibodies that do not neutralize primary isolate (tier 2) HIV-1 strains can protect from infection. In this study, we investigated the ability of an attenuated poxvirus vector (NYVAC) prime-envelope gp120 boost to elicit potentially protective antibody responses in a rhesus macaque model of mucosal simian-human immunodeficiency virus (SHIV) infection. NYVAC vector delivery of a group M consensus envelope, trivalent mosaic envelopes, or a natural clade B isolate B.1059 envelope elicited antibodies that mediated neutralization of tier 1 viruses, cellular cytotoxicity, and phagocytosis. None of the macaques made neutralizing antibodies against the tier 2 SHIV SF162P3 used for mucosal challenge. Significant protection from infection was not observed for the three groups of vaccinated macaques compared to unvaccinated macaques, although binding antibody to HIV-1 Env correlated with decreased viremia after challenge. Thus, NYVAC Env prime-gp120 boost vaccination elicited polyfunctional, nonneutralizing antibody responses with minimal protective activity against tier 2 SHIV mucosal challenge. IMPORTANCE The antibody responses that confer protection against HIV-1 infection remain unknown. Polyfunctional antibody responses correlated with time to infection in previous macaque studies. Determining the ability of vaccines to induce these types of responses is critical for understanding how to improve upon the one efficacious human HIV-1 vaccine trial completed thus far. We characterized the antibody responses induced by a NYVAC-protein vaccine and determined the protective capacity of polyfunctional antibody responses in an R5, tier 2 mucosal SHIV infection model. Copyright © 2018 American Society for Microbiology.

  10. The nucleus pararaphales in the human, chimpanzee, and macaque monkey.

    Science.gov (United States)

    Baizer, Joan S; Weinstock, Nadav; Witelson, Sandra F; Sherwood, Chet C; Hof, Patrick R

    2013-03-01

    The human cerebral cortex and cerebellum are greatly expanded compared to those of other mammals, including the great apes. This expansion is reflected in differences in the size and organization of precerebellar brainstem structures, such as the inferior olive. In addition, there are cell groups unique to the human brainstem. One such group may be the nucleus pararaphales (PRa); however, there is disagreement among authors about the size and location of this nucleus in the human brainstem. The name "pararaphales" has also been used for neurons in the medulla shown to project to the flocculus in the macaque monkey. We have re-examined the existence and status of the PRa in eight humans, three chimpanzees, and four macaque monkeys using Nissl-stained sections as well as immunohistochemistry. In the human we found a cell group along the midline of the medulla in all cases; it had the form of interrupted cell columns and was variable among cases in rostrocaudal and dorsoventral extent. Cells and processes were highly immunoreactive for non-phosphorylated neurofilament protein (NPNFP); somata were immunoreactive to the synthetic enzyme for nitric oxide, nitric oxide synthase, and for calretinin. In macaque monkey, there was a much smaller oval cell group with NPNFP immunoreactivity. In the chimpanzee, we found a region of NPNFP-immunoreactive cells and fibers similar to what was observed in macaques. These results suggest that the "PRa" in the human may not be the same structure as the flocculus-projecting cell group described in the macaque. The PRa, like the arcuate nucleus, therefore may be unique to humans.

  11. Pharmacokinetics of Cefovecin in Cynomolgus Macaques (Macaca fascicularis), Olive Baboons (Papio anubis), and Rhesus Macaques (Macaca mulatto)

    Energy Technology Data Exchange (ETDEWEB)

    Raabe, Brigitte M.; Lovaglio, Jamie A.; Grover, GScott; Brown, Scott A.; Boucher, Joseph F.; Yuan, Yang; Civil, Jacqueline R.; Gillhouse, Kimberly A.; Stubbs, Makeida N.; Hoggatt, Amber F.; Halliday, Lisa C.; Fortman, Jeffrey D.

    2011-05-01

    Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatto) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 {+-} 1.47 h in cynomolgus macaques, 9.17 {+-} 1.84 h in olive baboons, and 8.40 {+-} 2.53 h in rhesus macaques. These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.

  12. FLU VACCINATION

    CERN Multimedia

    2007-01-01

    People working on the CERN site who wish to be vaccinated may go to the Infirmary (ground-floor, bldg. 57), with their vaccine, without a prior appointment. The vaccine can be reimbursed directly by Uniqa providing you attach the receipt and the prescription that you will receive from the Medical Service the day of your injection at the infirmary. Ideally, the vaccination should take place between 1st October and 30th November 2007 (preferably between 14:00 and 16:00). CERN staff aged 50 or over are recommended to have influenza vaccinations. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and those convalescing from serious medical problems or after serious surgical operations. The Medical Service will not administer vaccines for family members or retired staff members, who must contact their normal family doctor. Medical Service

  13. Yersinia pestis biovar Microtus strain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques.

    Science.gov (United States)

    Zhang, Qingwen; Wang, Qiong; Tian, Guang; Qi, Zhizhen; Zhang, Xuecan; Wu, Xiaohong; Qiu, Yefeng; Bi, Yujing; Yang, Xiaoyan; Xin, Youquan; He, Jian; Zhou, Jiyuan; Zeng, Lin; Yang, Ruifu; Wang, Xiaoyi

    2014-01-01

    Yersinia pestis biovar Microtus is considered to be a virulent to larger mammals, including guinea pigs, rabbits and humans. It may be used as live attenuated plague vaccine candidates in terms of its low virulence. However, the Microtus strain's protection against plague has yet to be demonstrated in larger mammals. In this study, we evaluated the protective efficacy of the Microtus strain 201 as a live attenuated plague vaccine candidate. Our results show that this strain is highly attenuated by subcutaneous route, elicits an F1-specific antibody titer similar to the EV and provides a protective efficacy similar to the EV against bubonic plague in Chinese-origin rhesus macaques. The Microtus strain 201 could induce elevated secretion of both Th1-associated cytokines (IFN-γ, IL-2 and TNF-α) and Th2-associated cytokines (IL-4, IL-5, and IL-6), as well as chemokines MCP-1 and IL-8. However, the protected animals developed skin ulcer at challenge site with different severity in most of the immunized and some of the EV-immunized monkeys. Generally, the Microtus strain 201 represented a good plague vaccine candidate based on its ability to generate strong humoral and cell-mediated immune responses as well as its good protection against high dose of subcutaneous virulent Y. pestis challenge.

  14. Characterization of the rhesus macaque (Macaca mulatta) scrub typhus model: Susceptibility to intradermal challenge with the human pathogen Orientia tsutsugamushi Karp

    Science.gov (United States)

    Sunyakumthorn, Piyanate; Somponpun, Suwit J.; Im-erbsin, Rawiwan; Anantatat, Tippawan; Jenjaroen, Kemajittra; Dunachie, Susanna J.; Lombardini, Eric D.; Burke, Robin L.; Blacksell, Stuart D.; Jones, James W.; Mason, Carl J.; Richards, Allen L.; Day, Nicholas P. J.

    2018-01-01

    Background Scrub typhus is an important endemic disease in tropical Asia caused by Orientia tsutsugamushi for which no effective broadly protective vaccine is available. The successful evaluation of vaccine candidates requires well-characterized animal models and a better understanding of the immune response against O. tsutsugamushi. While many animal species have been used to study host immunity and vaccine responses in scrub typhus, only limited data exists in non-human primate (NHP) models. Methodology/Principle findings In this study we evaluated a NHP scrub typhus disease model based on intradermal inoculation of O. tsutsugamushi Karp strain in rhesus macaques (n = 7). After an intradermal inoculation with 106 murine LD50 of O. tsutsugamushi at the anterior thigh (n = 4) or mock inoculum (n = 3), a series of time course investigations involving hematological, biochemical, molecular and immunological assays were performed, until day 28, when tissues were collected for pathology and immunohistochemistry. In all NHPs with O. tsutsugamushi inoculation, but not with mock inoculation, the development of a classic eschar with central necrosis, regional lymphadenopathy, and elevation of body temperature was observed on days 7–21 post inoculation (pi); bacteremia was detected by qPCR on days 6–18 pi; and alteration of liver enzyme function and increase of white blood cells on day 14 pi. Immune assays demonstrated raised serum levels of soluble cell adhesion molecules, anti-O. tsutsugamushi-specific antibody responses (IgM and IgG) and pathogen-specific cell-mediated immune responses in inoculated macaques. The qPCR assays detected O. tsutsugamushi in eschar, spleen, draining and non-draining lymph nodes, and immuno-double staining demonstrated intracellular O. tsutsugamushi in antigen presenting cells of eschars and lymph nodes. Conclusions/Significance These data show the potential of using rhesus macaques as a scrub typhus model, for evaluation of correlates of

  15. Hepatitis Vaccines

    Directory of Open Access Journals (Sweden)

    Sina Ogholikhan

    2016-03-01

    Full Text Available Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver.

  16. Hepatitis Vaccines

    Science.gov (United States)

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  17. Route of delivery to the airway influences the distribution of pulmonary disease but not the outcome of Mycobacterium tuberculosis infection in rhesus macaques.

    Science.gov (United States)

    Sibley, Laura; Dennis, Mike; Sarfas, Charlotte; White, Andrew; Clark, Simon; Gleeson, Fergus; McIntyre, Anthony; Rayner, Emma; Pearson, Geoffrey; Williams, Ann; Marsh, Philip; Sharpe, Sally

    2016-01-01

    Non-human primates (NHP) provide a key component in the preclinical assessment pathway for new TB vaccines. In the established models, Mycobacterium tuberculosis challenge is typically delivered to airways of macaques either by aerosol or bronchoscopic instillation and therefore, an understanding of these delivery routes would facilitate the comparison of data generated from models using different challenge methods. This study compared the clinical effects, antigen-specific IFNγ response profiles and disease burden following delivery of comparable doses of M. tuberculosis to the lungs of rhesus macaques by either aerosol or bronchoscopic instillation. The outcome of infection in terms of clinical effects and overall disease burden was comparable between both routes of challenge. However, the pathology in the lungs differed as disease was localised to the site of inoculation following bronchoscopic instillation while aerosol exposure resulted in lesions being evenly distributed through the lung. Whilst the IFNγ response to PPD was similar, responses to CFP10 and ESAT6 peptide pools measured with an ex vivo ELISPOT differed with regards to responses to the N-terminal regions depending on the route of infection. Both challenge routes therefore provide valid and comparable models for evaluation of new TB vaccines, although subtle differences in host responses may occur. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Immunogenicity of seven new recombinant yellow fever viruses 17D expressing fragments of SIVmac239 Gag, Nef, and Vif in Indian rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Mauricio A Martins

    Full Text Available An effective vaccine remains the best solution to stop the spread of human immunodeficiency virus (HIV. Cellular immune responses have been repeatedly associated with control of viral replication and thus may be an important element of the immune response that must be evoked by an efficacious vaccine. Recombinant viral vectors can induce potent T-cell responses. Although several viral vectors have been developed to deliver HIV genes, only a few have been advanced for clinical trials. The live-attenuated yellow fever vaccine virus 17D (YF17D has many properties that make it an attractive vector for AIDS vaccine regimens. YF17D is well tolerated in humans and vaccination induces robust T-cell responses that persist for years. Additionally, methods to manipulate the YF17D genome have been established, enabling the generation of recombinant (rYF17D vectors carrying genes from unrelated pathogens. Here, we report the generation of seven new rYF17D viruses expressing fragments of simian immunodeficiency virus (SIVmac239 Gag, Nef, and Vif. Studies in Indian rhesus macaques demonstrated that these live-attenuated vectors replicated in vivo, but only elicited low levels of SIV-specific cellular responses. Boosting with recombinant Adenovirus type-5 (rAd5 vectors resulted in robust expansion of SIV-specific CD8(+ T-cell responses, particularly those targeting Vif. Priming with rYF17D also increased the frequency of CD4(+ cellular responses in rYF17D/rAd5-immunized macaques compared to animals that received rAd5 only. The effect of the rYF17D prime on the breadth of SIV-specific T-cell responses was limited and we also found evidence that some rYF17D vectors were more effective than others at priming SIV-specific T-cell responses. Together, our data suggest that YF17D - a clinically relevant vaccine vector - can be used to prime AIDS virus-specific T-cell responses in heterologous prime boost regimens. However, it will be important to optimize rYF17D

  19. Flu Vaccination

    CERN Multimedia

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  20. Flu vaccination

    CERN Multimedia

    CERN Medical Service

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor.CERN Medical Service

  1. FLU VACCINATION

    CERN Multimedia

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  2. Flu Vaccination

    CERN Multimedia

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical service

  3. Characterization of 47 MHC class I sequences in Filipino cynomolgus macaques

    Science.gov (United States)

    Campbell, Kevin J.; Detmer, Ann M.; Karl, Julie A.; Wiseman, Roger W.; Blasky, Alex J.; Hughes, Austin L.; Bimber, Benjamin N.; O’Connor, Shelby L.; O’Connor, David H.

    2009-01-01

    Cynomolgus macaques (Macaca fascicularis) provide increasingly common models for infectious disease research. Several geographically distinct populations of these macaques from Southeast Asia and the Indian Ocean island of Mauritius are available for pathogenesis studies. Though host genetics may profoundly impact results of such studies, similarities and differences between populations are often overlooked. In this study we identified 47 full-length MHC class I nucleotide sequences in 16 cynomolgus macaques of Filipino origin. The majority of MHC class I sequences characterized (39 of 47) were unique to this regional population. However, we discovered eight sequences with perfect identity and six sequences with close similarity to previously defined MHC class I sequences from other macaque populations. We identified two ancestral MHC haplotypes that appear to be shared between Filipino and Mauritian cynomolgus macaques, notably a Mafa-B haplotype that has previously been shown to protect Mauritian cynomolgus macaques against challenge with a simian/human immunodeficiency virus, SHIV89.6P. We also identified a Filipino cynomolgus macaque MHC class I sequence for which the predicted protein sequence differs from Mamu-B*17 by a single amino acid. This is important because Mamu-B*17 is strongly associated with protection against simian immunodeficiency virus (SIV) challenge in Indian rhesus macaques. These findings have implications for the evolutionary history of Filipino cynomolgus macaques as well as for the use of this model in SIV/SHIV research protocols. PMID:19107381

  4. Identification and characterization of short tandem repeats in the Tibetan macaque genome based on resequencing data.

    Science.gov (United States)

    Liu, San-Xu; Hou, Wei; Zhang, Xue-Yan; Peng, Chang-Jun; Yue, Bi-Song; Fan, Zhen-Xin; Li, Jing

    2018-07-18

    The Tibetan macaque, which is endemic to China, is currently listed as a Near Endangered primate species by the International Union for Conservation of Nature (IUCN). Short tandem repeats (STRs) refer to repetitive elements of genome sequence that range in length from 1-6 bp. They are found in many organisms and are widely applied in population genetic studies. To clarify the distribution characteristics of genome-wide STRs and understand their variation among Tibetan macaques, we conducted a genome-wide survey of STRs with next-generation sequencing of five macaque samples. A total of 1 077 790 perfect STRs were mined from our assembly, with an N50 of 4 966 bp. Mono-nucleotide repeats were the most abundant, followed by tetra- and di-nucleotide repeats. Analysis of GC content and repeats showed consistent results with other macaques. Furthermore, using STR analysis software (lobSTR), we found that the proportion of base pair deletions in the STRs was greater than that of insertions in the five Tibetan macaque individuals (Pgenome showed good amplification efficiency and could be used to study population genetics in Tibetan macaques. The neighbor-joining tree classified the five macaques into two different branches according to their geographical origin, indicating high genetic differentiation between the Huangshan and Sichuan populations. We elucidated the distribution characteristics of STRs in the Tibetan macaque genome and provided an effective method for screening polymorphic STRs. Our results also lay a foundation for future genetic variation studies of macaques.

  5. A microneedle patch containing measles vaccine is immunogenic in non-human primates.

    Science.gov (United States)

    Edens, Chris; Collins, Marcus L; Goodson, James L; Rota, Paul A; Prausnitz, Mark R

    2015-09-08

    Very high vaccination coverage is required to eliminate measles, but achieving high coverage can be constrained by the logistical challenges associated with subcutaneous injection. To simplify the logistics of vaccine delivery, a patch containing micron-scale polymeric needles was formulated to encapsulate the standard dose of measles vaccine (1000 TCID₅₀) and the immunogenicity of the microneedle patch was compared with subcutaneous injection in rhesus macaques. The microneedle patch was administered without reconstitution with diluent, dissolved in skin within 10 min, and caused only mild, transient skin erythema. Both groups of rhesus macaques generated neutralizing antibody responses to measles that were consistent with protection and the neutralizing antibody titers were equivalent. In addition, the microneedle patches maintained an acceptable level of potency after storage at elevated temperature suggesting improved thermostability compared to standard lyophilized vaccine. In conclusion, a measles microneedle patch vaccine was immunogenic in non-human primates, and this approach offers a promising delivery method that could help increase vaccination coverage. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Development of a Lethal Intranasal Exposure Model of Ebola Virus in the Cynomolgus Macaque

    Directory of Open Access Journals (Sweden)

    Kendra J. Alfson

    2017-10-01

    Full Text Available Ebola virus (EBOV is a filovirus that can cause Ebola virus disease (EVD. No approved vaccines or therapies exist for filovirus infections, despite an urgent need. The development and testing of effective countermeasures against EBOV requires use of animal models and a thorough understanding of how the model aligns with EVD in humans. The majority of published studies report outcomes of parenteral exposures for emulating needle stick transmission. However, based on data from EVD outbreaks, close contact exposures to infected bodily fluid seems to be one of the primary routes of EBOV transmission. Thus, further work is needed to develop models that represent mucosal exposure. To characterize the outcome of mucosal exposure to EBOV, cynomolgus macaques were exposed to EBOV via intranasal (IN route using the LMA® mucosal atomization device (LMA® MAD. For comparison, four non-human primates (NHPs were exposed to EBOV via intramuscular (IM route. This IN exposure model was uniformly lethal and correlated with a statistically significant delay in time to death when compared to exposure via the IM route. This more closely reflects the timeframes observed in human infections. An IN model of exposure offers an attractive alternative to other models as it can offer insight into the consequences of exposure via a mucosal surface and allows for screening countermeasures via a different exposure route.

  7. Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.

    Directory of Open Access Journals (Sweden)

    Félicien Moukambi

    2015-12-01

    Full Text Available Follicular T helper cells (Tfh, a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.

  8. Testosterone correlates with Venezuelan equine encephalitis virus infection in macaques

    Directory of Open Access Journals (Sweden)

    Koterski James

    2006-03-01

    Full Text Available Abstract Here we briefly report testosterone and cytokine responses to Venezuelan equine encephalitis virus (VEEV in macaques which were used as part of a larger study conducted by the Department of Defense to better characterize pathological responses to aerosolized VEEV in non-human primates. Serial samples were collected and analyzed for testosterone and cytokines prior to and during infection in 8 captive male macaques. Infected animals exhibited a febrile response with few significant changes in cytokine levels. Baseline testosterone levels were positively associated with viremia following exposure and were significantly higher than levels obtained during infection. Such findings suggest that disease-induced androgen suppression is a reasonable area for future study. Decreased androgen levels during physiological perturbations may function, in part, to prevent immunosuppression by high testosterone levels and to prevent the use of energetic resources for metabolically-expensive anabolic functions.

  9. Molecular and functional aspects of menstruation in the macaque.

    Science.gov (United States)

    Brenner, Robert M; Slayden, Ov D

    2012-12-01

    Much of our understanding of the molecular control of menstruation arises from laboratory models that experimentally recapitulate some, but not all, aspects of uterine bleeding observed in women. These models include: in vitro culture of endometrial explants or isolated endometrial cells, transplantation of human endometrial tissue into immunodeficient mice and the induction of endometrial breakdown in appropriately pretreated mice. Each of these models has contributed to our understanding of molecular and cellular mechanisms of menstruation, but nonhuman primates, especially macaques, are the animal model of choice for evaluating therapies for menstrual disorders. In this chapter we review some basic aspects of menstruation, with special emphasis on the macaque model and its relevance to the clinical issues of irregular and heavy menstrual bleeding (HMB).

  10. Radiographic changes in rhesus macaques affected by scurvy

    International Nuclear Information System (INIS)

    Morgan, J.P.; Eisele, P.H.

    1992-01-01

    Spontaneous vitamin C deficiency, or scurvy, was recognized in juvenile rhesus monkeys maintained in a research center as a result of being fed a commercial diet for 2 to 3 months with low levels of vitamin C. Most severely affected animals (13) were radiographed repeatedly up to day 300 following detection of the disease. Early radiographic changes consisted of widened, lucent metaphyses with lateral flaring and radiopaque metaphyseal lines at the junction of the metaphyses and physes. Physeal slippage was noted commonly. Following institution of vitamin C therapy, calcification of subperiosteal hemorrhage occurred in the metaphyseal regions. Metaphyses and physes returned to normal radiographic appearance within 15 to 30 days. Initially, the subperiosteal hemorrhage progressed and a longer time was required for solution of the calcified hematomas. The macaques improved clinically and were released from the hospital when fractures were stable at 4-5 weeks after admission. Of the 13 macaques studied, all but one returned as normal members of the colony

  11. Astrocyte atrophy and immune dysfunction in self-harming macaques.

    Science.gov (United States)

    Lee, Kim M; Chiu, Kevin B; Sansing, Hope A; Inglis, Fiona M; Baker, Kate C; MacLean, Andrew G

    2013-01-01

    Self-injurious behavior (SIB) is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP) and Toll-like receptor 2 (TLR2). Morphologic features of astrocytes were determined using computer-assisted camera lucida. There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

  12. Evolutionary and biomedical insights from the rhesus macaque genome.

    Science.gov (United States)

    Gibbs, Richard A; Rogers, Jeffrey; Katze, Michael G; Bumgarner, Roger; Weinstock, George M; Mardis, Elaine R; Remington, Karin A; Strausberg, Robert L; Venter, J Craig; Wilson, Richard K; Batzer, Mark A; Bustamante, Carlos D; Eichler, Evan E; Hahn, Matthew W; Hardison, Ross C; Makova, Kateryna D; Miller, Webb; Milosavljevic, Aleksandar; Palermo, Robert E; Siepel, Adam; Sikela, James M; Attaway, Tony; Bell, Stephanie; Bernard, Kelly E; Buhay, Christian J; Chandrabose, Mimi N; Dao, Marvin; Davis, Clay; Delehaunty, Kimberly D; Ding, Yan; Dinh, Huyen H; Dugan-Rocha, Shannon; Fulton, Lucinda A; Gabisi, Ramatu Ayiesha; Garner, Toni T; Godfrey, Jennifer; Hawes, Alicia C; Hernandez, Judith; Hines, Sandra; Holder, Michael; Hume, Jennifer; Jhangiani, Shalini N; Joshi, Vandita; Khan, Ziad Mohid; Kirkness, Ewen F; Cree, Andrew; Fowler, R Gerald; Lee, Sandra; Lewis, Lora R; Li, Zhangwan; Liu, Yih-Shin; Moore, Stephanie M; Muzny, Donna; Nazareth, Lynne V; Ngo, Dinh Ngoc; Okwuonu, Geoffrey O; Pai, Grace; Parker, David; Paul, Heidie A; Pfannkoch, Cynthia; Pohl, Craig S; Rogers, Yu-Hui; Ruiz, San Juana; Sabo, Aniko; Santibanez, Jireh; Schneider, Brian W; Smith, Scott M; Sodergren, Erica; Svatek, Amanda F; Utterback, Teresa R; Vattathil, Selina; Warren, Wesley; White, Courtney Sherell; Chinwalla, Asif T; Feng, Yucheng; Halpern, Aaron L; Hillier, Ladeana W; Huang, Xiaoqiu; Minx, Pat; Nelson, Joanne O; Pepin, Kymberlie H; Qin, Xiang; Sutton, Granger G; Venter, Eli; Walenz, Brian P; Wallis, John W; Worley, Kim C; Yang, Shiaw-Pyng; Jones, Steven M; Marra, Marco A; Rocchi, Mariano; Schein, Jacqueline E; Baertsch, Robert; Clarke, Laura; Csürös, Miklós; Glasscock, Jarret; Harris, R Alan; Havlak, Paul; Jackson, Andrew R; Jiang, Huaiyang; Liu, Yue; Messina, David N; Shen, Yufeng; Song, Henry Xing-Zhi; Wylie, Todd; Zhang, Lan; Birney, Ewan; Han, Kyudong; Konkel, Miriam K; Lee, Jungnam; Smit, Arian F A; Ullmer, Brygg; Wang, Hui; Xing, Jinchuan; Burhans, Richard; Cheng, Ze; Karro, John E; Ma, Jian; Raney, Brian; She, Xinwei; Cox, Michael J; Demuth, Jeffery P; Dumas, Laura J; Han, Sang-Gook; Hopkins, Janet; Karimpour-Fard, Anis; Kim, Young H; Pollack, Jonathan R; Vinar, Tomas; Addo-Quaye, Charles; Degenhardt, Jeremiah; Denby, Alexandra; Hubisz, Melissa J; Indap, Amit; Kosiol, Carolin; Lahn, Bruce T; Lawson, Heather A; Marklein, Alison; Nielsen, Rasmus; Vallender, Eric J; Clark, Andrew G; Ferguson, Betsy; Hernandez, Ryan D; Hirani, Kashif; Kehrer-Sawatzki, Hildegard; Kolb, Jessica; Patil, Shobha; Pu, Ling-Ling; Ren, Yanru; Smith, David Glenn; Wheeler, David A; Schenck, Ian; Ball, Edward V; Chen, Rui; Cooper, David N; Giardine, Belinda; Hsu, Fan; Kent, W James; Lesk, Arthur; Nelson, David L; O'brien, William E; Prüfer, Kay; Stenson, Peter D; Wallace, James C; Ke, Hui; Liu, Xiao-Ming; Wang, Peng; Xiang, Andy Peng; Yang, Fan; Barber, Galt P; Haussler, David; Karolchik, Donna; Kern, Andy D; Kuhn, Robert M; Smith, Kayla E; Zwieg, Ann S

    2007-04-13

    The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

  13. Rectal HSV-2 Infection May Increase Rectal SIV Acquisition Even in the Context of SIVΔnef Vaccination.

    Directory of Open Access Journals (Sweden)

    Natalia Guerra-Pérez

    Full Text Available Prevalent HSV-2 infection increases the risk of HIV acquisition both in men and women even in asymptomatic subjects. Understanding the impact of HSV-2 on the mucosal microenvironment may help to identify determinants of susceptibility to HIV. Vaginal HSV-2 infection increases the frequency of cells highly susceptible to HIV in the vaginal tissue of women and macaques and this correlates with increased susceptibility to vaginal SHIV infection in macaques. However, the effect of rectal HSV-2 infection on HIV acquisition remains understudied. We developed a model of rectal HSV-2 infection in macaques in combination with rectal SIVmac239Δnef (SIVΔnef vaccination and our results suggest that rectal HSV-2 infection may increase the susceptibility of macaques to rectal SIVmac239 wild-type (wt infection even in SIVΔnef-infected animals. Rectal SIVΔnef infection/vaccination protected 7 out of 7 SIVΔnef-infected macaques from SIVmac239wt rectal infection (vs 12 out of 16 SIVΔnef-negative macaques, while 1 out of 3 animals co-infected with SIVΔnef and HSV-2 acquired SIVmac239wt infection. HSV-2/SIVmac239wt co-infected animals had increased concentrations of inflammatory factors in their plasma and rectal fluids and a tendency toward higher acute SIVmac239wt plasma viral load. However, they had higher blood CD4 counts and reduced depletion of CCR5+ CD4+ T cells compared to SIVmac239wt-only infected animals. Thus, rectal HSV-2 infection generates a pro-inflammatory environment that may increase susceptibility to rectal SIV infection and may impact immunological and virological parameters during acute SIV infection. Studies with larger number of animals are needed to confirm these findings.

  14. Spontaneous extracutaneous systemic mastocytosis in a cynomolgus macaque ()

    OpenAIRE

    Martina , Z. Zöller; Joachim , Kaspareit

    2010-01-01

    Abstract A uniform cell population of proliferating mast cells with poor cytoplasmic granularity and few eosinophilic infiltrates was observed in hepatic portal tracts and the cecal submucosa of an adult male cynomolgus macaque (Macaca fascicularis) that was part of a drug safety assessment toxicity study. The proliferating mast cells were positive for Giemsa and toluidine blue staining and had strong immunoreactivity for mast cell tryptase and CD68. Considering size, morphology, i...

  15. Social interactions through the eyes of macaques and humans.

    Directory of Open Access Journals (Sweden)

    Richard McFarland

    Full Text Available Group-living primates frequently interact with each other to maintain social bonds as well as to compete for valuable resources. Observing such social interactions between group members provides individuals with essential information (e.g. on the fighting ability or altruistic attitude of group companions to guide their social tactics and choice of social partners. This process requires individuals to selectively attend to the most informative content within a social scene. It is unclear how non-human primates allocate attention to social interactions in different contexts, and whether they share similar patterns of social attention to humans. Here we compared the gaze behaviour of rhesus macaques and humans when free-viewing the same set of naturalistic images. The images contained positive or negative social interactions between two conspecifics of different phylogenetic distance from the observer; i.e. affiliation or aggression exchanged by two humans, rhesus macaques, Barbary macaques, baboons or lions. Monkeys directed a variable amount of gaze at the two conspecific individuals in the images according to their roles in the interaction (i.e. giver or receiver of affiliation/aggression. Their gaze distribution to non-conspecific individuals was systematically varied according to the viewed species and the nature of interactions, suggesting a contribution of both prior experience and innate bias in guiding social attention. Furthermore, the monkeys' gaze behavior was qualitatively similar to that of humans, especially when viewing negative interactions. Detailed analysis revealed that both species directed more gaze at the face than the body region when inspecting individuals, and attended more to the body region in negative than in positive social interactions. Our study suggests that monkeys and humans share a similar pattern of role-sensitive, species- and context-dependent social attention, implying a homologous cognitive mechanism of

  16. Distributed acoustic cues for caller identity in macaque vocalization.

    Science.gov (United States)

    Fukushima, Makoto; Doyle, Alex M; Mullarkey, Matthew P; Mishkin, Mortimer; Averbeck, Bruno B

    2015-12-01

    Individual primates can be identified by the sound of their voice. Macaques have demonstrated an ability to discern conspecific identity from a harmonically structured 'coo' call. Voice recognition presumably requires the integrated perception of multiple acoustic features. However, it is unclear how this is achieved, given considerable variability across utterances. Specifically, the extent to which information about caller identity is distributed across multiple features remains elusive. We examined these issues by recording and analysing a large sample of calls from eight macaques. Single acoustic features, including fundamental frequency, duration and Weiner entropy, were informative but unreliable for the statistical classification of caller identity. A combination of multiple features, however, allowed for highly accurate caller identification. A regularized classifier that learned to identify callers from the modulation power spectrum of calls found that specific regions of spectral-temporal modulation were informative for caller identification. These ranges are related to acoustic features such as the call's fundamental frequency and FM sweep direction. We further found that the low-frequency spectrotemporal modulation component contained an indexical cue of the caller body size. Thus, cues for caller identity are distributed across identifiable spectrotemporal components corresponding to laryngeal and supralaryngeal components of vocalizations, and the integration of those cues can enable highly reliable caller identification. Our results demonstrate a clear acoustic basis by which individual macaque vocalizations can be recognized.

  17. DNA Vaccines

    Indian Academy of Sciences (India)

    diseases. Keywords. DNA vaccine, immune response, antibodies, infectious diseases. GENERAL .... tein vaccines require expensive virus/protein purification tech- niques as ... sphere continue to remain major health hazards in developing nations. ... significance since it can be produced at a very low cost and can be stored ...

  18. Vaccination Policies

    NARCIS (Netherlands)

    Verweij, M.F.

    2013-01-01

    Vaccination involves priming the immune system with an antigenic agent that mimics a virus or bacterium, which results in immunity against the “real” microorganism. Collective vaccination policies have played an important role in the control of infectious disease worldwide. They can serve the

  19. TUMOUR VACCINE

    NARCIS (Netherlands)

    Wagner, Ernst; Kircheis, Ralf; Crommelin, D.; Van Slooten, Maaike; Storm, Gert

    1999-01-01

    The invention relates to a tumour vaccine with a tumour antigen base. In addition to a source of tumour antigens, the vaccine contains a release system for the delayed release of the active agent IFN- gamma , the active dose of IFN- gamma being 50 ng to 5 mu g. The IFN- gamma is released over a

  20. Rotavirus Vaccine

    Science.gov (United States)

    Why get vaccinated?Rotavirus is a virus that causes diarrhea, mostly in babies and young children. The diarrhea can be severe, and lead ... and fever are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common ...

  1. Evidence for a role for interleukin-17, Th17 cells and iron homeostasis in protective immunity against tuberculosis in cynomolgus macaques.

    Science.gov (United States)

    Wareham, Alice S; Tree, Julia A; Marsh, Philip D; Butcher, Philip D; Dennis, Mike; Sharpe, Sally A

    2014-01-01

    Tuberculosis (TB) remains a major global public health problem. The only vaccine, BCG, gives variable protection, especially in adults, so several new vaccines are in clinical trials. There are no correlates of protective immunity to TB; therefore vaccines progress through lengthy and expensive pre-clinical assessments and human trials. Correlates of protection could act as early end-points during clinical trials, accelerating vaccine development and reducing costs. A genome-wide microarray was utilised to identify potential correlates of protection and biomarkers of disease induced post-BCG vaccination and post-Mycobacterium tuberculosis challenge in PPD-stimulated peripheral blood mononuclear cells from cynomolgus macaques where the outcome of infection was known. Gene expression post BCG-vaccination and post challenge was compared with gene expression when the animals were naïve. Differentially expressed genes were identified using a moderated T test with Benjamini Hochberg multiple testing correction. After BCG vaccination and six weeks post-M. tuberculosis challenge, up-regulation of genes related to a Th1 and Th17 response was observed in disease controllers. At post-mortem, RT-PCR revealed an up-regulation of iron regulatory genes in animals that developed TB and down-regulation of these genes in disease controllers, indicating the ability to successfully withhold iron may be important in the control of TB disease. The induction of a balanced Th1 and Th17 response, together with expression of effector cytokines, such as IFNG, IL2, IL17, IL21 and IL22, could be used as correlates of a protective host response.

  2. Evidence for a role for interleukin-17, Th17 cells and iron homeostasis in protective immunity against tuberculosis in cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Alice S Wareham

    Full Text Available Tuberculosis (TB remains a major global public health problem. The only vaccine, BCG, gives variable protection, especially in adults, so several new vaccines are in clinical trials. There are no correlates of protective immunity to TB; therefore vaccines progress through lengthy and expensive pre-clinical assessments and human trials. Correlates of protection could act as early end-points during clinical trials, accelerating vaccine development and reducing costs. A genome-wide microarray was utilised to identify potential correlates of protection and biomarkers of disease induced post-BCG vaccination and post-Mycobacterium tuberculosis challenge in PPD-stimulated peripheral blood mononuclear cells from cynomolgus macaques where the outcome of infection was known. Gene expression post BCG-vaccination and post challenge was compared with gene expression when the animals were naïve. Differentially expressed genes were identified using a moderated T test with Benjamini Hochberg multiple testing correction. After BCG vaccination and six weeks post-M. tuberculosis challenge, up-regulation of genes related to a Th1 and Th17 response was observed in disease controllers. At post-mortem, RT-PCR revealed an up-regulation of iron regulatory genes in animals that developed TB and down-regulation of these genes in disease controllers, indicating the ability to successfully withhold iron may be important in the control of TB disease. The induction of a balanced Th1 and Th17 response, together with expression of effector cytokines, such as IFNG, IL2, IL17, IL21 and IL22, could be used as correlates of a protective host response.

  3. Directed shift of vaginal microbiota induced by vaginal application of sucrose gel in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Kai-tao Hu

    2015-04-01

    Conclusions: Rhesus macaques can be used as animal models of bacterial vaginosis to develop drugs and test treatment efficacy. Furthermore, the topical application of sucrose gel induced the shifting of vaginal flora of rhesus macaques from a BV kind of flora to a lactobacilli-dominating flora.

  4. Interindividual Differences in Neonatal Imitation and the Development of Action Chains in Rhesus Macaques

    Science.gov (United States)

    Ferrari, Pier Francesco; Paukner, Annika; Ruggiero, Angela; Darcey, Lisa; Unbehagen, Sarah; Suomi, Stephen J.

    2009-01-01

    The capacity to imitate facial gestures is highly variable in rhesus macaques and this variability may be related to differences in specific neurobehavioral patterns of development. This study evaluated the differential neonatal imitative response of 41 macaques in relation to the development of sensory, motor, and cognitive skills throughout the…

  5. Correction of refractive errors in rhesus macaques (Macaca mulatta) involved in visual research.

    Science.gov (United States)

    Mitchell, Jude F; Boisvert, Chantal J; Reuter, Jon D; Reynolds, John H; Leblanc, Mathias

    2014-08-01

    Macaques are the most common animal model for studies in vision research, and due to their high value as research subjects, often continue to participate in studies well into old age. As is true in humans, visual acuity in macaques is susceptible to refractive errors. Here we report a case study in which an aged macaque demonstrated clear impairment in visual acuity according to performance on a demanding behavioral task. Refraction demonstrated bilateral myopia that significantly affected behavioral and visual tasks. Using corrective lenses, we were able to restore visual acuity. After correction of myopia, the macaque's performance on behavioral tasks was comparable to that of a healthy control. We screened 20 other male macaques to assess the incidence of refractive errors and ocular pathologies in a larger population. Hyperopia was the most frequent ametropia but was mild in all cases. A second macaque had mild myopia and astigmatism in one eye. There were no other pathologies observed on ocular examination. We developed a simple behavioral task that visual research laboratories could use to test visual acuity in macaques. The test was reliable and easily learned by the animals in 1 d. This case study stresses the importance of screening macaques involved in visual science for refractive errors and ocular pathologies to ensure the quality of research; we also provide simple methodology for screening visual acuity in these animals.

  6. Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques

    DEFF Research Database (Denmark)

    Yan, Guangmei; Zhang, Guojie; Fang, Xiaodong

    2011-01-01

    The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus...

  7. High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus

    Science.gov (United States)

    Nalca, Aysegul; Rossi, Franco D.; Miller, Lynn J.; Wiley, Michael R.; Perez-Sautu, Unai; Washington, Samuel C.; Norris, Sarah L.; Wollen-Roberts, Suzanne E.; Shamblin, Joshua D.; Kimmel, Adrienne E.; Bloomfield, Holly A.; Valdez, Stephanie M.; Sprague, Thomas R.; Principe, Lucia M.; Bellanca, Stephanie A.; Cinkovich, Stephanie S.; Lugo-Roman, Luis; Cazares, Lisa H.; Pratt, William D.; Palacios, Gustavo F.; Bavari, Sina; Pitt, M. Louise; Nasar, Farooq

    2017-01-01

    Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present. PMID:28548637

  8. High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus.

    Science.gov (United States)

    Haddow, Andrew D; Nalca, Aysegul; Rossi, Franco D; Miller, Lynn J; Wiley, Michael R; Perez-Sautu, Unai; Washington, Samuel C; Norris, Sarah L; Wollen-Roberts, Suzanne E; Shamblin, Joshua D; Kimmel, Adrienne E; Bloomfield, Holly A; Valdez, Stephanie M; Sprague, Thomas R; Principe, Lucia M; Bellanca, Stephanie A; Cinkovich, Stephanie S; Lugo-Roman, Luis; Cazares, Lisa H; Pratt, William D; Palacios, Gustavo F; Bavari, Sina; Pitt, M Louise; Nasar, Farooq

    2017-08-01

    Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present.

  9. Whither vaccines?

    Science.gov (United States)

    Rodrigues, Charlene M C; Pinto, Marta V; Sadarangani, Manish; Plotkin, Stanley A

    2017-06-01

    Currently used vaccines have had major effects on eliminating common infections, largely by duplicating the immune responses induced by natural infections. Now vaccinology faces more complex problems, such as waning antibody, immunosenescence, evasion of immunity by the pathogen, deviation of immunity by the microbiome, induction of inhibitory responses, and complexity of the antigens required for protection. Fortunately, vaccine development is now incorporating knowledge from immunology, structural biology, systems biology and synthetic chemistry to meet these challenges. In addition, international organisations are developing new funding and licensing pathways for vaccines aimed at pathogens with epidemic potential that emerge from tropical areas. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  10. Rhesus macaques (Macaca mulatta are natural hosts of specific Staphylococcus aureus lineages.

    Directory of Open Access Journals (Sweden)

    Sanne van den Berg

    Full Text Available Currently, there is no animal model known that mimics natural nasal colonization by Staphylococcus aureus in humans. We investigated whether rhesus macaques are natural nasal carriers of S. aureus. Nasal swabs were taken from 731 macaques. S. aureus isolates were typed by pulsed-field gel electrophoresis (PFGE, spa repeat sequencing and multi-locus sequence typing (MLST, and compared with human strains. Furthermore, the isolates were characterized by several PCRs. Thirty-nine percent of 731 macaques were positive for S. aureus. In general, the macaque S. aureus isolates differed from human strains as they formed separate PFGE clusters, 50% of the isolates were untypeable by agr genotyping, 17 new spa types were identified, which all belonged to new sequence types (STs. Furthermore, 66% of macaque isolates were negative for all superantigen genes. To determine S. aureus nasal colonization, three nasal swabs from 48 duo-housed macaques were taken during a 5 month period. In addition, sera were analyzed for immunoglobulin G and A levels directed against 40 staphylococcal proteins using a bead-based flow cytometry technique. Nineteen percent of the animals were negative for S. aureus, and 17% were three times positive. S. aureus strains were easily exchanged between macaques. The antibody response was less pronounced in macaques compared to humans, and nasal carrier status was not associated with differences in serum anti-staphylococcal antibody levels. In conclusion, rhesus macaques are natural hosts of S. aureus, carrying host-specific lineages. Our data indicate that rhesus macaques are useful as an autologous model for studying S. aureus nasal colonization and infection prevention.

  11. Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone.

    Science.gov (United States)

    Li, Xiao-Feng; Dong, Hao-Long; Wang, Hong-Jiang; Huang, Xing-Yao; Qiu, Ye-Feng; Ji, Xue; Ye, Qing; Li, Chunfeng; Liu, Yang; Deng, Yong-Qiang; Jiang, Tao; Cheng, Gong; Zhang, Fu-Chun; Davidson, Andrew D; Song, Ya-Jun; Shi, Pei-Yong; Qin, Cheng-Feng

    2018-02-14

    The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.

  12. Influenza vaccination

    DEFF Research Database (Denmark)

    Østerhus, Sven Frederick

    2015-01-01

    The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....

  13. Flu Vaccine Safety Information

    Science.gov (United States)

    ... Influenza Types Seasonal Avian Swine Variant Pandemic Other Flu Vaccine Safety Information Questions & Answers Language: English (US) ... safety of flu vaccines monitored? Egg Allergy Are flu vaccines safe? Flu vaccines have good safety record. ...

  14. Thimerosal in Flu Vaccine

    Science.gov (United States)

    ... Seasonal Avian Swine Variant Pandemic Other Thimerosal in Flu Vaccine Questions & Answers Language: English (US) Español Recommend ... and/or fungi from contaminating the vaccine. Do flu vaccines contain thimerosal? Flu vaccines in multi-dose ...

  15. Ear Infection and Vaccines

    Science.gov (United States)

    ... an ENT Doctor Near You Ear Infection and Vaccines Ear Infection and Vaccines Patient Health Information News ... or may need reinsertion over time. What about vaccines? A vaccine is a preparation administered to stimulate ...

  16. Antipneumococcal vaccination

    Directory of Open Access Journals (Sweden)

    Gian Vincenzo Zuccotti

    2013-06-01

    Full Text Available Streptococcus pneumoniae (SP is a gram-positive bacterium with more than 90 known serotypes causing around 11% of all deaths worldwide in children aged 1-59 months. A new era in prevention of SP-related diseases started in at the beginning of 2000s when a 7-valent pneumococcal conjugate vaccine (PCV7 was recommended as the vaccine of choice in pediatric age. PCV7 dramatically reduced invasive pneumococcal diseases (IPD among children with indirect effects noted among other age groups as well. However, thanks to a strict surveillance network, an increase in non-vaccine serotypes (NVTs causing IPD was noted worldwide and in late 2000s a new second generation vaccine (13-valent pneumococcal conjugate vaccine-PCV13 with an expanded serotype coverage was licensed. Due to the lack of solid effectiveness data, up to know it is difficult to predict how the composition of NVTs will change after the large-scale introduction of PCV13 or whether the characteristics of the serotypes will change. Long-term surveillance of both IPD, pneumonia, acute otitis media and carriage will be crucial to ascertain whether these second generation vaccines are having the desired effect of reducing the incidence of diseases in the long term. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  17. A critical period of progesterone withdrawal precedes menstruation in macaques

    Science.gov (United States)

    Slayden, Ov D; Brenner, Robert M

    2006-01-01

    Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12–24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked. PMID:17118170

  18. Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques.

    Directory of Open Access Journals (Sweden)

    Nami Suzuki-Hashido

    Full Text Available Bitter taste receptors (TAS2R proteins allow mammals to detect and avoid ingestion of toxins in food. Thus, TAS2Rs play an important role in food choice and are subject to complex natural selection pressures. In our previous study, we examined nucleotide variation in TAS2R38, a gene expressing bitter taste receptor for phenylthiocarbamide (PTC, in 333 Japanese macaques (Macaca fuscata from 9 local populations in Japan. We identified a PTC "non-taster" TAS2R38 allele in Japanese macaques that was caused by a loss of the start codon. This PTC non-taster allele was only found in a limited local population (the Kii area, at a frequency of 29%. In this study, we confirmed that this allele was present in only the Kii population by analyzing an additional 264 individuals from eight new populations. Using cellular and behavioral experiments, we found that this allele lost its receptor function for perceiving PTC. The nucleotide sequences of the allele including flanking regions (of about 10 kb from 23 chromosomes were identical, suggesting that a non-taster allele arose and expanded in the Kii population during the last 13,000 years. Genetic analyses of non-coding regions in Kii individuals and neighboring populations indicated that the high allele frequency in the Kii population could not be explained by demographic history, suggesting that positive selection resulted in a rapid increase in PTC non-tasters in the Kii population. The loss-of-function that occurred at the TAS2R38 locus presumably provided a fitness advantage to Japanese macaques in the Kii population. Because TAS2R38 ligands are often found in plants, this functional change in fitness is perhaps related to feeding habit specificity. These findings should provide valuable insights for elucidating adaptive evolutionary changes with respect to various environments in wild mammals.

  19. Seroconversion to HCoV-NL63 in Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Lia van der Hoek

    2009-10-01

    Full Text Available HCoV-NL63 is a recently identified respiratory virus. Its pathogenesis has not been fully unraveled because an animal model is currently lacking. Here we examined whether rhesus macaques encounter HCoV-NL63 infections during life, by examining the levels of antibodies to HCoV-NL63 in time. The animals were followed for 7 up till 19 years, and in three animals we observed a steep rise in antibodies during follow up, indicative of a natural infection with HCoV-NL63.

  20. Improved survival in rhesus macaques immunized with modified vaccinia virus Ankara recombinants expressing simian immunodeficiency virus envelope correlates with reduction in memory CD4+ T-cell loss and higher titers of neutralizing antibody.

    Science.gov (United States)

    Ourmanov, Ilnour; Kuwata, Takeo; Goeken, Robert; Goldstein, Simoy; Iyengar, Ranjani; Buckler-White, Alicia; Lafont, Bernard; Hirsch, Vanessa M

    2009-06-01

    Previous studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high viremia and AIDS following challenge with a pathogenic strain of SIV. Although all animals became infected, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines compared with animals that received nonrecombinant MVA. Most importantly, the reduction in viremia resulted in a significant increase in median and cumulative survival. Continued analysis of these animals over the subsequent 9 years has shown that they maintain a survival advantage, although all but two of the macaques have progressed to AIDS. Importantly, improved survival correlated with preservation of memory CD4(+) T cells in the peripheral blood. The greatest survival advantage was observed in macaques immunized with regimens containing SIV Env, and the titer of neutralizing antibodies to the challenge virus prior to or shortly following challenge correlated with preservation of CD4(+) T cells. These data are consistent with a role for neutralizing antibodies in nonsterilizing protection from high viremia and associated memory CD4(+) T-cell loss.

  1. ABO blood group phenotype frequency estimation using molecular phenotyping in rhesus and cynomolgus macaques.

    Science.gov (United States)

    Kanthaswamy, S; Ng, J; Oldt, R F; Valdivia, L; Houghton, P; Smith, D G

    2017-11-01

    A much larger sample (N = 2369) was used to evaluate a previously reported distribution of the A, AB and B blood group phenotypes in rhesus and cynomolgus macaques from six different regional populations. These samples, acquired from 15 different breeding and research facilities in the United States, were analyzed using a real-time quantitative polymerase chain reaction (qPCR) assay that targets single nucleotide polymorphisms (SNPs) responsible for the macaque A, B and AB phenotypes. The frequency distributions of blood group phenotypes of the two species differ significantly from each other and significant regional differentiation within the geographic ranges of each species was also observed. The B blood group phenotype was prevalent in rhesus macaques, especially those from India, while the frequencies of the A, B and AB phenotypes varied significantly among cynomolgus macaques from different geographic regions. The Mauritian cynomolgus macaques, despite having originated in Indonesia, showed significant (P ≪ .01) divergence from the Indonesian animals at the ABO blood group locus. Most Mauritian animals belonged to the B blood group while the Indonesian animals were mostly A. The close similarity in blood group frequency distributions between the Chinese rhesus and Indochinese cynomolgus macaques demonstrates that the introgression between these two species extends beyond the zone of intergradation in Indochina. This study underscores the importance of ABO blood group phenotyping of the domestic supply of macaques and their biospecimens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Estimation of Shear Wave Speed in the Rhesus Macaques Uterine Cervix

    Science.gov (United States)

    Huang, Bin; Drehfal, Lindsey C.; Rosado-Mendez, Ivan M.; Guerrero, Quinton W.; Palmeri, Mark L.; Simmons, Heather A.; Feltovich, Helen; Hall, Timothy J.

    2016-01-01

    Cervical softness is a critical parameter in pregnancy. Clinically, preterm birth is associated with premature cervical softening and post-dates birth is associated with delayed cervical softening. In practice, the assessment of softness is subjective, based on digital examination. Fortunately, objective, quantitative techniques to assess softness and other parameters associated with microstructural cervical change are emerging. One of these is shear wave speed (SWS) estimation. In principle, this allows objective characterization of stiffness because waves travel more slowly in softer tissue. We are studying SWS in humans and rhesus macaques, the latter in order to accelerate translation from bench to bedside. For the current study, we estimated SWS in ex vivo cervices of rhesus macaques, n=24 nulliparous (never given birth) and n=9 multiparous (delivered at least 1 baby). Misoprostol (a prostaglandin used to soften human cervices prior to gynecological procedures) was administered to 13 macaques prior to necropsy (nulliparous: 7, multiparous: 6). SWS measurements were made at predetermined locations from the distal to proximal end of the cervix on both the anterior and posterior cervix, with 5 repeat measures at each location. The intent was to explore macaque cervical microstructure, including biological and spatial variability, to elucidate the similarities and differences between the macaque and the human cervix in order to facilitate future in vivo studies. We found that SWS is dependent on location in the normal nonpregnant macaque cervix, as in the human cervix. Unlike the human cervix, we detected no difference between ripened and unripened rhesus macaque cervix samples, nor nulliparous versus multiparous samples, although we observed a trend toward stiffer tissue in nulliparous samples. We found rhesus macaque cervix to be much stiffer than human, which is important for technique refinement. These findings are useful for guiding study of cervical

  3. Th1-skewed tissue responses to a mycolyl glycolipid in mycobacteria-infected rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Daisuke; Miyamoto, Ayumi; Hattori, Yuki; Komori, Takaya [Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Nakamura, Takashi [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Igarashi, Tatsuhiko [Laboratory of Primate Model, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Harashima, Hideyoshi [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Sugita, Masahiko [Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan)

    2013-11-08

    Highlights: •Glucose monomycolate (GMM) is a marker glycolipid for active tuberculosis. •Tissue responses to GMM involved up-regulation of Th1-attracting chemokines. •Th1-skewed local responses were mounted at the GMM-injected tissue. -- Abstract: Trehalose 6,6′-dimycolate (TDM) is a major glycolipid of the cell wall of mycobacteria with remarkable adjuvant functions. To avoid detection by the host innate immune system, invading mycobacteria down-regulate the expression of TDM by utilizing host-derived glucose as a competitive substrate for their mycolyltransferases; however, this enzymatic reaction results in the concomitant biosynthesis of glucose monomycolate (GMM) which is recognized by the acquired immune system. GMM-specific, CD1-restricted T cell responses have been detected in the peripheral blood of infected human subjects and monkeys as well as in secondary lymphoid organs of small animals, such as guinea pigs and human CD1-transgenic mice. Nevertheless, it remains to be determined how tissues respond at the site where GMM is produced. Here we found that rhesus macaques vaccinated with Mycobacterium bovis bacillus Calmette–Guerin mounted a chemokine response in GMM-challenged skin that was favorable for recruiting T helper (Th)1 T cells. Indeed, the expression of interferon-γ, but not Th2 or Th17 cytokines, was prominent in the GMM-injected tissue. The GMM-elicited tissue response was also associated with the expression of monocyte/macrophage-attracting CC chemokines, such as CCL2, CCL4 and CCL8. Furthermore, the skin response to GMM involved the up-regulated expression of granulysin and perforin. Given that GMM is produced primarily by pathogenic mycobacteria proliferating within the host, the Th1-skewed tissue response to GMM may function efficiently at the site of infection.

  4. Th1-skewed tissue responses to a mycolyl glycolipid in mycobacteria-infected rhesus macaques

    International Nuclear Information System (INIS)

    Morita, Daisuke; Miyamoto, Ayumi; Hattori, Yuki; Komori, Takaya; Nakamura, Takashi; Igarashi, Tatsuhiko; Harashima, Hideyoshi; Sugita, Masahiko

    2013-01-01

    Highlights: •Glucose monomycolate (GMM) is a marker glycolipid for active tuberculosis. •Tissue responses to GMM involved up-regulation of Th1-attracting chemokines. •Th1-skewed local responses were mounted at the GMM-injected tissue. -- Abstract: Trehalose 6,6′-dimycolate (TDM) is a major glycolipid of the cell wall of mycobacteria with remarkable adjuvant functions. To avoid detection by the host innate immune system, invading mycobacteria down-regulate the expression of TDM by utilizing host-derived glucose as a competitive substrate for their mycolyltransferases; however, this enzymatic reaction results in the concomitant biosynthesis of glucose monomycolate (GMM) which is recognized by the acquired immune system. GMM-specific, CD1-restricted T cell responses have been detected in the peripheral blood of infected human subjects and monkeys as well as in secondary lymphoid organs of small animals, such as guinea pigs and human CD1-transgenic mice. Nevertheless, it remains to be determined how tissues respond at the site where GMM is produced. Here we found that rhesus macaques vaccinated with Mycobacterium bovis bacillus Calmette–Guerin mounted a chemokine response in GMM-challenged skin that was favorable for recruiting T helper (Th)1 T cells. Indeed, the expression of interferon-γ, but not Th2 or Th17 cytokines, was prominent in the GMM-injected tissue. The GMM-elicited tissue response was also associated with the expression of monocyte/macrophage-attracting CC chemokines, such as CCL2, CCL4 and CCL8. Furthermore, the skin response to GMM involved the up-regulated expression of granulysin and perforin. Given that GMM is produced primarily by pathogenic mycobacteria proliferating within the host, the Th1-skewed tissue response to GMM may function efficiently at the site of infection

  5. Genetic Divergence of the Rhesus Macaque Major Histocompatibility Complex

    Science.gov (United States)

    Daza-Vamenta, Riza; Glusman, Gustavo; Rowen, Lee; Guthrie, Brandon; Geraghty, Daniel E.

    2004-01-01

    The major histocompatibility complex (MHC) is comprised of the class I, class II, and class III regions, including the MHC class I and class II genes that play a primary role in the immune response and serve as an important model in studies of primate evolution. Although nonhuman primates contribute significantly to comparative human studies, relatively little is known about the genetic diversity and genomics underlying nonhuman primate immunity. To address this issue, we sequenced a complete rhesus macaque MHC spanning over 5.3 Mb, and obtained an additional 2.3 Mb from a second haplotype, including class II and portions of class I and class III. A major expansion of from six class I genes in humans to as many as 22 active MHC class I genes in rhesus and levels of sequence divergence some 10-fold higher than a similar human comparison were found, averaging from 2% to 6% throughout extended portions of class I and class II. These data pose new interpretations of the evolutionary constraints operating between MHC diversity and T-cell selection by contrasting with models predicting an optimal number of antigen presenting genes. For the clinical model, these data and derivative genetic tools can be implemented in ongoing genetic and disease studies that involve the rhesus macaque. PMID:15289473

  6. Risk Factors for Dystocia in Pigtailed Macaques (Macaca nemestrina)

    Science.gov (United States)

    Stockinger, Diane E; Torrence, Anne E; Hukkanen, Renee R; Vogel, Keith W; Hotchkiss, Charlotte E; Ha, James C

    2011-01-01

    Dystocia (difficult labor) is an important component of the management of nonhuman primates and results in significant fetal and maternal morbidity and increased use of veterinary resources. Dystocias can arise from abnormalities of the maternal pelvis or fetus or uncoordinated uterine activity. Although risk factors for stillbirths have been established in nonhuman primates, risk factors for dystocias have not. The objective of this study was to determine maternal and fetal risk factors for dystocia in macaques. Retrospective data were collected from 83 pigtailed macaques (Macaca nemestrina) diagnosed with dystocia. The diagnosis of dystocia was made based on clinical or pathologic evidence. Maternal records of age, reproductive history, experimental history, clinical records, and fetal birth weight and any applicable fetal necropsy reports were reviewed. The gestational age of the fetus, the infant's birth weight, total previous births by the dam, and the proportions of both viable delivery (inverse effect) and surgical pregnancy interventions (direct effect) in the dam's history generated a model that maximized the experimental variance for predicting dystocia in the current pregnancy and explained 24% of the dystocia deliveries. The number of total previous births and proportion of previous cesarean sections accounted for the greatest effect. This model can identify individual dams within a colony that are at risk for dystocias and allow for changes in breeding colony management, more intense monitoring of dams at risk, or allocation of additional resources. PMID:21535929

  7. Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain.

    Science.gov (United States)

    Noguchi, Kevin K; Johnson, Stephen A; Manzella, Francesca M; Masuoka, Kobe L; Williams, Sasha L; Martin, Lauren D; Dissen, Gregory A; Ikonomidou, Chrysanthy; Schenning, Katie J; Olney, John W; Brambrink, Ansgar M

    2018-03-28

    Caffeine is the most frequently used medication in premature infants. It is the respiratory stimulant of choice for apnea associated with prematurity and has been called the silver bullet in neonatology because of many proven benefits and few known risks. Research has revealed that sedative/anesthetic drugs trigger apoptotic death of neurons and oligodendrocytes in developing mammalian brains. Here we evaluated the influence of caffeine on the neurotoxicity of anesthesia in developing nonhuman primate brains. Fetal macaques (n = 7-8/group), at a neurodevelopmental age comparable to premature human infants, were exposed in utero for 5 hours to no drug (control), isoflurane, or isoflurane + caffeine and examined for evidence of apoptosis. Isoflurane exposure increased apoptosis 3.3 fold for neurons and 3.4 fold for oligodendrocytes compared to control brains. Isoflurane + caffeine caused neuronal apoptosis to increase 8.0 fold compared to control levels but did not augment oligoapoptosis. Neuronal death was particularly pronounced in the basal ganglia and cerebellum. Higher blood levels of caffeine within the range considered therapeutic and safe for human infants correlated with increased neuroapoptosis. Caffeine markedly augments neurotoxicity of isoflurane in the fetal macaque brain and challenges the assumption that caffeine is safe for premature infants.

  8. Astrocyte atrophy and immune dysfunction in self-harming macaques.

    Directory of Open Access Journals (Sweden)

    Kim M Lee

    Full Text Available BACKGROUND: Self-injurious behavior (SIB is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. METHODS: We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP and Toll-like receptor 2 (TLR2. Morphologic features of astrocytes were determined using computer-assisted camera lucida. RESULTS: There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. CONCLUSIONS: These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

  9. Grooming reciprocity in female tibetan macaques macaca thibetana.

    Science.gov (United States)

    Xia, Dongpo; Li, Jinhua; Garber, Paul A; Sun, Lixing; Zhu, Yong; Sun, Binghua

    2012-06-01

    Grooming among nonhuman primates is widespread and may represent an important service commodity that is exchanged within a biological marketplace. In this study, using focal animal sampling methods, we recorded grooming relationships among 12 adult females in a free-ranging group of Tibetan macaques (Macaca thibetana) at Huangshan, China, to determine the influence of rank and kinship on grooming relationships, and whether females act as reciprocal traders (exchange grooming received for grooming given) or interchange traders (interchange grooming for social tolerance or other commodities). The results showed that: (1) grooming given was positively correlated with grooming received; (2) kinship did not exert a significant influence on grooming reciprocity; and (3) grooming reciprocity occurred principally between individuals of adjacent rank; however, when females of different rank groomed, females tended to groom up the hierarchy (lower ranking individuals groomed higher ranking individuals more than vice versa). Our results support the contention that both grooming reciprocity and the interchange of grooming for tolerance represent important social tactics used by female Tibetan macaques. © 2012 Wiley Periodicals, Inc.

  10. Macaques can predict social outcomes from facial expressions.

    Science.gov (United States)

    Waller, Bridget M; Whitehouse, Jamie; Micheletta, Jérôme

    2016-09-01

    There is widespread acceptance that facial expressions are useful in social interactions, but empirical demonstration of their adaptive function has remained elusive. Here, we investigated whether macaques can use the facial expressions of others to predict the future outcomes of social interaction. Crested macaques (Macaca nigra) were shown an approach between two unknown individuals on a touchscreen and were required to choose between one of two potential social outcomes. The facial expressions of the actors were manipulated in the last frame of the video. One subject reached the experimental stage and accurately predicted different social outcomes depending on which facial expressions the actors displayed. The bared-teeth display (homologue of the human smile) was most strongly associated with predicted friendly outcomes. Contrary to our predictions, screams and threat faces were not associated more with conflict outcomes. Overall, therefore, the presence of any facial expression (compared to neutral) caused the subject to choose friendly outcomes more than negative outcomes. Facial expression in general, therefore, indicated a reduced likelihood of social conflict. The findings dispute traditional theories that view expressions only as indicators of present emotion and instead suggest that expressions form part of complex social interactions where individuals think beyond the present.

  11. Particle-to-PFU ratio of Ebola virus influences disease course and survival in cynomolgus macaques.

    Science.gov (United States)

    Alfson, Kendra J; Avena, Laura E; Beadles, Michael W; Staples, Hilary; Nunneley, Jerritt W; Ticer, Anysha; Dick, Edward J; Owston, Michael A; Reed, Christopher; Patterson, Jean L; Carrion, Ricardo; Griffiths, Anthony

    2015-07-01

    This study addresses the role of Ebola virus (EBOV) specific infectivity in virulence. Filoviruses are highly lethal, enveloped, single-stranded negative-sense RNA viruses that can cause hemorrhagic fever. No approved vaccines or therapies exist for filovirus infections, and infectious virus must be handled in maximum containment. Efficacy testing of countermeasures, in addition to investigations of pathogenicity and immune response, often requires a well-characterized animal model. For EBOV, an obstacle in performing accurate disease modeling is a poor understanding of what constitutes an infectious dose in animal models. One well-recognized consequence of viral passage in cell culture is a change in specific infectivity, often measured as a particle-to-PFU ratio. Here, we report that serial passages of EBOV in cell culture resulted in a decrease in particle-to-PFU ratio. Notably, this correlated with decreased potency in a lethal cynomolgus macaque (Macaca fascicularis) model of infection; animals were infected with the same viral dose as determined by plaque assay, but animals that received more virus particles exhibited increased disease. This suggests that some particles are unable to form a plaque in a cell culture assay but are able to result in lethal disease in vivo. These results have a significant impact on how future studies are designed to model EBOV disease and test countermeasures. Ebola virus (EBOV) can cause severe hemorrhagic disease with a high case-fatality rate, and there are no approved vaccines or therapies. Specific infectivity can be considered the total number of viral particles per PFU, and its impact on disease is poorly understood. In stocks of most mammalian viruses, there are particles that are unable to complete an infectious cycle or unable to cause cell pathology in cultured cells. We asked if these particles cause disease in nonhuman primates by infecting monkeys with equal infectious doses of genetically identical stocks

  12. Green revolution vaccines, edible vaccines | Tripurani | African ...

    African Journals Online (AJOL)

    Edible vaccines are sub-unit vaccines where the selected genes are introduced into the plants and the transgenic plant is then induced to manufacture the encoded protein. Edible vaccines are mucosal-targeted vaccines where stimulation of both systematic and mucosal immune network takes place. Foods under study ...

  13. A genetically engineered live-attenuated simian-human immunodeficiency virus that co-expresses the RANTES gene improves the magnitude of cellular immunity in rhesus macaques

    International Nuclear Information System (INIS)

    Shimizu, Yuya; Inaba, Katsuhisa; Kaneyasu, Kentaro; Ibuki, Kentaro; Himeno, Ai; Okoba, Masashi; Goto, Yoshitaka; Hayami, Masanori; Miura, Tomoyuki; Haga, Takeshi

    2007-01-01

    Regulated-on-activation-normal-T-cell-expressed-and-secreted (RANTES), a CC-chemokine, enhances antigen-specific T helper (Th) type-1 responses against HIV-1. To evaluate the adjuvant effects of RANTES against HIV vaccine candidate in SHIV-macaque models, we genetically engineered a live-attenuated SHIV to express the RANTES gene (SHIV-RANTES) and characterized the virus's properties in vivo. After the vaccination, the plasma viral loads were same in the SHIV-RANTES-inoculated monkeys and the parental nef-deleted SHIV (SHIV-NI)-inoculated monkeys. SHIV-RANTES provided some immunity in monkeys by remarkably increasing the antigen-specific CD4 + Th cell-proliferative response and by inducing an antigen-specific IFN-γ ELISpot response. The magnitude of the immunity in SHIV-RANTES-immunized animals, however, failed to afford greater protection against a heterologous pathogenic SHIV (SHIV-C2/1) challenge compared to control SHIV-NI-immunized animals. SHIV-RANTES immunized monkeys, elicited robust cellular CD4 + Th responses and IFN-γ ELISpot responses after SHIV-C2/1 challenge. These findings suggest that the chemokine RANTES can augment vaccine-elicited, HIV-specific CD4 + T cell responses

  14. Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Shufang Fan

    2009-05-01

    Full Text Available The continued spread of highly pathogenic H5N1 influenza viruses among poultry and wild birds, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. Inactivated subvirion or whole-virion H5N1 vaccines have shown promising immunogenicity in clinical trials, but their ability to elicit protective immunity in unprimed human populations remains unknown. A cold-adapted, live attenuated vaccine with the hemagglutinin (HA and neuraminidase (NA genes of an H5N1 virus A/VN/1203/2004 (clade 1 was protective against the pulmonary replication of homologous and heterologous wild-type H5N1 viruses in mice and ferrets. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H5N1 vaccine (AH/AAca that contains HA and NA genes from a recent H5N1 isolate, A/Anhui/2/05 virus (AH/05 (clade 2.3, and the backbone of the cold-adapted influenza H2N2 A/AnnArbor/6/60 virus (AAca. AH/AAca was attenuated in chickens, mice, and monkeys, and it induced robust neutralizing antibody responses as well as HA-specific CD4+ T cell immune responses in rhesus macaques immunized twice intranasally. Importantly, the vaccinated macaques were fully protected from challenge with either the homologous AH/05 virus or a heterologous H5N1 virus, A/bar-headed goose/Qinghai/3/05 (BHG/05; clade 2.2. These results demonstrate for the first time that a cold-adapted H5N1 vaccine can elicit protective immunity against highly pathogenic H5N1 virus infection in a nonhuman primate model and provide a compelling argument for further testing of double immunization with live attenuated H5N1 vaccines in human trials.

  15. Vesicular stomatitis virus-based ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Thomas W Geisbert

    2008-11-01

    Full Text Available Ebola virus (EBOV is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVDeltaG/ZEBOVGP in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV. All six animals showed no evidence of illness associated with the VSVDeltaG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV.

  16. Evidence that emotion mediates social attention in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Emily J Bethell

    Full Text Available BACKGROUND: Recent work on non-human primates indicates that the allocation of social attention is mediated by characteristics of the attending animal, such as social status and genotype, as well as by the value of the target to which attention is directed. Studies of humans indicate that an individual's emotion state also plays a crucial role in mediating their social attention; for example, individuals look for longer towards aggressive faces when they are feeling more anxious, and this bias leads to increased negative arousal and distraction from other ongoing tasks. To our knowledge, no studies have tested for an effect of emotion state on allocation of social attention in any non-human species. METHODOLOGY: We presented captive adult male rhesus macaques with pairs of adult male conspecific face images - one with an aggressive expression, one with a neutral expression - and recorded gaze towards these images. Each animal was tested twice, once during a putatively stressful condition (i.e. following a veterinary health check, and once during a neutral (or potentially positive condition (i.e. a period of environmental enrichment. Initial analyses revealed that behavioural indicators of anxiety and stress were significantly higher after the health check than during enrichment, indicating that the former caused a negative shift in emotional state. PRINCIPLE FINDINGS: The macaques showed initial vigilance for aggressive faces across both conditions, but subsequent responses differed between conditions. Following the health check, initial vigilance was followed by rapid and sustained avoidance of aggressive faces. By contrast, during the period of enrichment, the macaques showed sustained attention towards the same aggressive faces. CONCLUSIONS/SIGNIFICANCE: These data provide, to our knowledge, the first evidence that shifts in emotion state mediate social attention towards and away from facial cues of emotion in a non-human animal. This work

  17. Valuing vaccination.

    Science.gov (United States)

    Bärnighausen, Till; Bloom, David E; Cafiero-Fonseca, Elizabeth T; O'Brien, Jennifer Carroll

    2014-08-26

    Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery.

  18. Use-Wear Patterns on Wild Macaque Stone Tools Reveal Their Behavioural History

    OpenAIRE

    Haslam, Michael; Gumert, Michael D.; Biro, Dora; Carvalho, Susana; Malaivijitnond, Suchinda

    2013-01-01

    Burmese long-tailed macaques (Macaca fascicularis aurea) are one of a limited number of wild animal species to use stone tools, with their tool use focused on pounding shelled marine invertebrates foraged from intertidal habitats. These monkeys exhibit two main styles of tool use: axe hammering of oysters, and pound hammering of unattached encased foods. In this study, we examined macroscopic use-wear patterns on a sample of 60 wild macaque stone tools from Piak Nam Yai Island, Thailand, that...

  19. Function and Innervation of the Locus Ceruleus in a Macaque Model of Functional Hypothalamic Amenorrhea

    OpenAIRE

    Bethea, Cynthia L; Kim, Aaron; Cameron, Judy L

    2012-01-01

    A body of knowledge implicates an increase in output from the locus ceruleus (LC) during stress. We questioned the innervation and function of the LC in our macaque model of Functional Hypothalamic Amenorrhea, also known as Stress-Induced Amenorrhea. Cohorts of macaques were initially characterized as highly stress resilient (HSR) or stress-sensitive (SS) based upon the presence or absence of ovulation during a protocol involving 2 menstrual cycles with psychosocial and metabolic stress. Afte...

  20. Social management of laboratory rhesus macaques housed in large groups using a network approach: A review.

    Science.gov (United States)

    McCowan, Brenda; Beisner, Brianne; Hannibal, Darcy

    2017-12-07

    Biomedical facilities across the nation and worldwide aim to develop cost-effective methods for the reproductive management of macaque breeding groups, typically by housing macaques in large, multi-male multi-female social groups that provide monkey subjects for research as well as appropriate socialization for their psychological well-being. One of the most difficult problems in managing socially housed macaques is their propensity for deleterious aggression. From a management perspective, deleterious aggression (as opposed to less intense aggression that serves to regulate social relationships) is undoubtedly the most problematic behavior observed in group-housed macaques, which can readily escalate to the degree that it causes social instability, increases serious physical trauma leading to group dissolution, and reduces psychological well-being. Thus for both welfare and other management reasons, aggression among rhesus macaques at primate centers and facilities needs to be addressed with a more proactive approach.Management strategies need to be instituted that maximize social housing while also reducing problematic social aggression due to instability using efficacious methods for detection and prevention in the most cost effective manner. Herein we review a new proactive approach using social network analysis to assess and predict deleterious aggression in macaque groups. We discovered three major pathways leading to instability, such as unusually high rates and severity of trauma and social relocations.These pathways are linked either directly or indirectly to network structure in rhesus macaque societies. We define these pathways according to the key intrinsic and extrinsic variables (e.g., demographic, genetic or social factors) that influence network and behavioral measures of stability (see Fig. 1). They are: (1) presence of natal males, (2) matrilineal genetic fragmentation, and (3) the power structure and conflict policing behavior supported by this

  1. Glial cell morphological and density changes through the lifespan of rhesus macaques.

    Science.gov (United States)

    Robillard, Katelyn N; Lee, Kim M; Chiu, Kevin B; MacLean, Andrew G

    2016-07-01

    How aging impacts the central nervous system (CNS) is an area of intense interest. Glial morphology is known to affect neuronal and immune function as well as metabolic and homeostatic balance. Activation of glia, both astrocytes and microglia, occurs at several stages during development and aging. The present study analyzed changes in glial morphology and density through the entire lifespan of rhesus macaques, which are physiologically and anatomically similar to humans. We observed apparent increases in gray matter astrocytic process length and process complexity as rhesus macaques matured from juveniles through adulthood. These changes were not attributed to cell enlargement because they were not accompanied by proportional changes in soma or process volume. There was a decrease in white matter microglial process length as rhesus macaques aged. Aging was shown to have a significant effect on gray matter microglial density, with a significant increase in aged macaques compared with adults. Overall, we observed significant changes in glial morphology as macaques age indicative of astrocytic activation with subsequent increase in microglial density in aged macaques. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Mycobacterium kansasii Isolated from Tuberculinpositive Rhesus Macaques (Macaca mulatta) in the Absence of Disease.

    Science.gov (United States)

    Shipley, Steven T; Johnson, David K; Roodgar, Morteza; Smith, David Glenn; Montgomery, Charles A; Lloyd, Steven M; Higgins, James A; Kriel, Edwin H; Klein, Hilton J; Porter, William P; Nazareno, Jerome B; Houghton, Paul W; Panda, Aruna; DeTolla, Louis J

    2017-08-01

    Mycobacterial infections are of primary health concern in NHP colonies in biomedical research. NHP are constantly monitored and screened for Mycobacterium spp. We report 6 Chinese-origin rhesus macaques infected with Mycobacterium kansasii that exhibited positive tuberculin skin tests in the absence of disease. Two of these macaques were being used for research purposes; the remaining 4 macaques were residing at the contract quarantine company. Histopathology and acid-fast staining of fixed tissues from all macaques showed that all were free of disease. Thoracic radiographs were negative for any signs of disease or infection. Samples from bronchial lavage and tissues including lung, spleen, hilar and mesenteric lymph nodes tested negative by PCR assay for Mycobacterium spp. One of the research macaques tested culture-positive for M. kansasii and a poorly characterized M. avium complex organism. One macaque from the contract quarantine facility tested culture positive for M. kansasii. Genomic testing and target gene RNA expression analysis of the 2 M. kansasii isolates were performed to evaluate possible kinship and affected genes that might contribute to susceptibility to mycobacterial infection. Genotyping of the 2 isolates revealed 2 genetically distinct strains (strains 1 and 4). The presence of positive tuberculin skin tests in the absence of disease raises serious concerns regarding diagnostic methods used for infected NHP.

  3. Toxicity and efficacy of 2',3'-dideoxycytidine in clinical trials of pigtailed macaques infected with simian retrovirus type 2.

    OpenAIRE

    Tsai, C C; Follis, K E; Yarnall, M; Blakley, G A

    1989-01-01

    Four dosing regimens of 2',3'-dideoxycytidine (ddC) were administered intravenously for 10 to 28 days to 18 pigtailed macaques with simian acquired immunodeficiency syndrome. Ten macaques naturally infected with simian acquired immunodeficiency syndrome retrovirus serotype 2 (SRV-2), the etiologic agent of simian acquired immunodeficiency syndrome, received ddC by continuous intravenous infusion or by a daily bolus injection for 10 to 12 days. Another eight macaques that were negative for SRV...

  4. Spatial and temporal vision of macaques after central retinal lesions

    International Nuclear Information System (INIS)

    Merigan, W.H.; Pasternak, T.; Zehl, D.

    1981-01-01

    Spatial contrast and temporal modulation sensitivity of two macaque monkeys were measured at three luminance levels before and after binocular laser coagulation of the fovea. The radius of the lesions ranged from 1.6 to 2.2 degree from the center of the fovea. After placement of the lesions, the visibility of high spatial frequencies was greatly reduced, although sensitivity at middle and low spatial frequencies was unaffected. No loss of spatial resolution was found at the lowest luminance tested. When temporal modulation sensitivity was tested with 4 deg targets, foveal lesions had no effect at any temporal frequency or luminance. However, with a 0.57 degree target, sensitivity to lower temporal frequencies was impaired. Thus visual loss after destruction of the fovea is limited to high luminance, small targets, and the resolution of fine detail

  5. Discovery of a secular trend in Cayo Santiago macaque reproduction.

    Science.gov (United States)

    Hernández-Pacheco, Raisa; Rawlins, Richard G; Kessler, Matthew J; Delgado, Diana L; Ruiz-Lambides, Angelina V; Sabat, Alberto M

    2016-02-01

    Reproductive synchrony and the consequent clustering of births are hypothesized to be regulated by seasonal changes in rainfall and food availability. Such climate-related seasonality is, however, questionable in tropical populations occupying temporally invariant habitats year round. Using the long-term data of the Cayo Santiago rhesus macaques from 1973 to 2013, this study distinguishes synchrony (a greater than chance clustering of births) from seasonality (a cluster of births during a period of the year when abiotic conditions are favorable) and shows that females are highly synchronized (>72% of births in a 3-month period) but the effects of environmental zeitgebers on reproduction are overridden by biological factors. Specifically, biotic and abiotic factors including (i) loss of immature offspring; (ii) population density; (iii) age at delivery; (iv) rainfall; and (v) changes in colony management were modeled in relation to the annual onset of births and the median birth date. Females experiencing loss of immature offspring had an interbirth interval of trend in both the onset of births and the median date of birth is documented and the model predicts that the median birth date will advance across all calendar-based seasons by 2050. The secular trend in reproduction appears to be triggered by changes in the age at delivery of females, the absence of physiological constraints from maternal investment due to offspring loss, shorter interbirth interval, and a higher degree of coordination due to increasing population density. This study challenges the reproductive phenology previously described for rhesus macaques highlighting the importance of long-term studies in addressing the ultimate causes of reproductive synchrony. © 2015 Wiley Periodicals, Inc.

  6. Acoustic characteristics used by Japanese macaques for individual discrimination.

    Science.gov (United States)

    Furuyama, Takafumi; Kobayasi, Kohta I; Riquimaroux, Hiroshi

    2017-10-01

    The vocalizations of primates contain information about speaker individuality. Many primates, including humans, are able to distinguish conspecifics based solely on vocalizations. The purpose of this study was to investigate the acoustic characteristics used by Japanese macaques in individual vocal discrimination. Furthermore, we tested human subjects using monkey vocalizations to evaluate species specificity with respect to such discriminations. Two monkeys and five humans were trained to discriminate the coo calls of two unfamiliar monkeys. We created a stimulus continuum between the vocalizations of the two monkeys as a set of probe stimuli (whole morph). We also created two sets of continua in which only one acoustic parameter, fundamental frequency ( f 0 ) or vocal tract characteristic (VTC), was changed from the coo call of one monkey to that of another while the other acoustic feature remained the same ( f 0 morph and VTC morph, respectively). According to the results, the reaction times both of monkeys and humans were correlated with the morph proportion under the whole morph and f 0 morph conditions. The reaction time to the VTC morph was correlated with the morph proportion in both monkeys, whereas the reaction time in humans, on average, was not correlated with morph proportion. Japanese monkeys relied more consistently on VTC than did humans for discriminating monkey vocalizations. Our results support the idea that the auditory system of primates is specialized for processing conspecific vocalizations and suggest that VTC is a significant acoustic feature used by Japanese macaques to discriminate conspecific vocalizations. © 2017. Published by The Company of Biologists Ltd.

  7. Depth perception from moving cast shadow in macaque monkey.

    Science.gov (United States)

    Mizutani, Saneyuki; Usui, Nobuo; Yokota, Takanori; Mizusawa, Hidehiro; Taira, Masato; Katsuyama, Narumi

    2015-07-15

    In the present study, we investigate whether the macaque monkey can perceive motion in depth using a moving cast shadow. To accomplish this, we conducted two experiments. In the first experiment, an adult Japanese monkey was trained in a motion discrimination task in depth by binocular disparity. A square was presented on the display so that it appeared with a binocular disparity of 0.12 degrees (initial position), and moved toward (approaching) or away from (receding) the monkey for 1s. The monkey was trained to discriminate the approaching and receding motion of the square by GO/delayed GO-type responses. The monkey showed a significantly high accuracy rate in the task, and the performance was maintained when the position, color, and shape of the moving object were changed. In the next experiment, the change in the disparity was gradually decreased in the motion discrimination task. The results showed that the performance of the monkey declined as the distance of the approaching and receding motion of the square decreased from the initial position. However, when a moving cast shadow was added to the stimulus, the monkey responded to the motion in depth induced by the cast shadow in the same way as by binocular disparity; the reward was delivered randomly or given in all trials to prevent the learning of the 2D motion of the shadow in the frontal plane. These results suggest that the macaque monkey can perceive motion in depth using a moving cast shadow as well as using binocular disparity. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Predictors of insubordinate aggression among captive female rhesus macaques.

    Science.gov (United States)

    Seil, Shannon K; Hannibal, Darcy L; Beisner, Brianne A; McCowan, Brenda

    2017-11-01

    Cercopithicine primates tend to have nepotistic hierarchies characterized by predictable, kinship-based dominance. Although aggression is typically directed down the hierarchy, insubordinate aggression does occur. Insubordination is important to understand because it can precipitate social upheaval and undermine group stability; however, the factors underlying it are not well understood. We test whether key social and demographic variables predict insubordination among captive female rhesus macaques. To identify factors influencing insubordination, multivariate analyses of 10,821 dyadic conflicts among rhesus macaque females were conducted, using data from six captive groups. A segmented regression analysis was used to identify dyads with insubordination. Negative binomial regression analyses and an information theoretic approach were used to assess predictors of insubordination among dyads. In the best models, weight difference (w = 1.0; IRR = 0.930), age (dominant: w = 1.0, IRR = 0.681; subordinate: w = 1.0, IRR = 1.069), the subordinate's total number of allies (w = 0.727, IRR = 1.060) or non-kin allies (w = 0.273, IRR = 1.165), the interaction of the dominant's kin allies and weight difference (w = 0.938, IRR = 1.046), violation of youngest ascendancy (w = 1.0; IRR = 2.727), and the subordinate's maternal support (w = 1.0; IRR = 2.928), are important predictors of insubordination. These results show that both intrinsic and social factors influence insubordinate behavior. This adds to evidence of the importance of intrinsic factors and flexibility in a social structure thought to be rigid and predetermined by external factors. Further, because insubordination can precipitate social overthrow, determining predictors of insubordination will shed light on mechanisms underlying stability in nepotistic societies. © 2017 Wiley Periodicals, Inc.

  9. Emotional states after grooming interactions in Japanese macaques (Macaca fuscata).

    Science.gov (United States)

    Ueno, Masataka; Yamada, Kazunori; Nakamichi, Masayuki

    2015-11-01

    In animal societies, the effect of grooming interactions on anxiety reduction is unclear. This study examined the effects of giving and receiving grooming on anxiety reduction in free ranging female Japanese macaques (Macaca fuscata) by measuring rates of self-scratching as an index of anxiety. In this study, the authors used a focal-animal sampling method, targeting 17 females at Katsuyama, Okayama prefecture, Japan. They evaluated affiliative relationships, which were defined by standard proximity rates, and found that females' self-scratching rates were lower after grooming affiliated partners than during matched-control periods (occurring on another day, beginning at approximately the same time of day as the corresponding postgrooming period) and not after grooming unaffiliated partners. Moreover, regardless of affiliative relationships, self-scratching rates were lower after receiving grooming than during matched-control periods. These findings did not change after excluding data in which groomer and groomee were in proximity after the grooming interaction. In addition, multivariable analysis showed that affiliative relationships, but not kinship or rank distances, were related to differences in the rates of self-scratching between giving grooming and matched-control periods. In contrast, neither affiliative relationships nor kinship nor rank distances affected differences in self-scratching rates between receiving grooming and matched-control periods. Therefore, individuals' anxiety levels decreased both after giving grooming to affiliated partners and after receiving grooming, regardless of affiliative relationships. This is the first empirical study to support the notion that giving grooming to affiliated partners is self-rewarding in Japanese macaques. (c) 2015 APA, all rights reserved).

  10. Vaccines and Thimerosal

    Science.gov (United States)

    ... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...

  11. Vaccine Adverse Events

    Science.gov (United States)

    ... for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More sharing ... in the primary immunization series in infants Report Adverse Event Report a Vaccine Adverse Event Contact FDA ( ...

  12. Vaccination in Fish

    DEFF Research Database (Denmark)

    Chettri, Jiwan Kumar

    vaccines have reduced the need for usage of antibiotics with more than 99 % since the 1980s. Fish can be vaccinated by three different administration routes: injection, immersion and oral vaccination. Injection vaccination (intraperitoneal injection of vaccine) is the most time consuming and labor...... intensive method, which however, provides the best protection of the fish. Immersion vaccination is used for immunization of a high number of small fish is cost-efficient and fast (30 sec immersion into vaccine). Oral vaccination (vaccine in feed) is the least efficient. As in higher vertebrates fish...... respond to vaccination by increasing the specific antibody titer and by activating the cellular responses. My talk will cover vaccination methods in fish, immune responses and some adverse effect of oil-adjuvanted vaccines in fish with reference to our work in rainbow trout, Oncorhynchus mykiss....

  13. Human Papillomavirus (HPV) Vaccine

    Science.gov (United States)

    Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...

  14. [Poliovirus vaccine].

    Science.gov (United States)

    Shimizu, Hiroyuki

    2012-06-01

    To avoid the risk of vaccine-associated paralytic poliomyelitis (VAPP) and polio outbreaks due to circulating vaccine-derived polioviruses, an inactivated poliovirus vaccine (IPV) was introduced for routine immunization in a number of countries with a low risk of polio outbreaks. Currently, production and marketing of a standalone conventional IPV and two diphtheria-pertussis-tetanus-IPV (Sabin-derived IPV; sIPV) products have been submitted, and it is expected that the IPV products will be introduced in Japan in the autumn of 2012. At the same time, a decline in the OPV immunization rate became apparent in Japan due to serious public concerns about a remaining risk of VAPP and introduction of IPV in the near future. Therefore, the recent development of polio immunity gaps should be carefully monitored, and surveillance of suspected polio cases and laboratory diagnosis of polioviruses have to be intensified for the transition period from OPV to IPV in Japan. The development of sIPV is one of the most realistic options to introduce affordable IPV to developing countries. In this regard, further clinical studies on its efficacy, safety, and interchangeability of sIPV will be needed after the introduction of the sIPV products, which will be licensed in Japan for the first time in the world.

  15. Hepatitis B Vaccine

    Science.gov (United States)

    ... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

  16. Diversity and molecular phylogeny of mitochondrial DNA of rhesus macaques (Macaca mulatta) in Bangladesh.

    Science.gov (United States)

    Hasan, M Kamrul; Feeroz, M Mostafa; Jones-Engel, Lisa; Engel, Gregory A; Kanthaswamy, Sree; Smith, David Glenn

    2014-11-01

    While studies of rhesus macaques (Macaca mulatta) in the eastern (e.g., China) and western (e.g., India) parts of their geographic range have revealed major genetic differences that warrant the recognition of two different subspecies, little is known about genetic characteristics of rhesus macaques in the transitional zone extending from eastern India and Bangladesh through the northern part of Indo-China, the probable original homeland of the species. We analyzed genetic variation of 762 base pairs of mitochondrial DNA from 86 fecal swab samples and 19 blood samples from 25 local populations of rhesus macaque in Bangladesh collected from January 2010 to August 2012. These sequences were compared with those of rhesus macaques from India, China, and Myanmar. Forty-six haplotypes defined by 200 (26%) polymorphic nucleotide sites were detected. Estimates of gene diversity, expected heterozygosity, and nucleotide diversity for the total population were 0.9599 ± 0.0097, 0.0193 ± 0.0582, and 0.0196 ± 0.0098, respectively. A mismatch distribution of paired nucleotide differences yielded a statistically significantly negative value of Tajima's D, reflecting a population that rapidly expanded after the terminal Pleistocene. Most haplotypes throughout regions of Bangladesh, including an isolated region in the southwestern area (Sundarbans), clustered with haplotypes assigned to the minor haplogroup Ind-2 from India reflecting an east to west dispersal of rhesus macaques to India. Haplotypes from the southeast region of Bangladesh formed a cluster with those from Myanmar, and represent the oldest rhesus macaque haplotypes of Bangladesh. These results are consistent with the hypothesis that rhesus macaques first entered Bangladesh from the southeast, probably from Indo-China, then dispersed westward throughout eastern and central India. © 2014 Wiley Periodicals, Inc.

  17. Ex-vivo α-galactosylceramide activation of NKT cells in humans and macaques.

    Science.gov (United States)

    Fernandez, Caroline S; Cameron, Garth; Godfrey, Dale I; Kent, Stephen J

    2012-08-31

    NKT cells are key mediators of antiviral and anticancer immunity. Experiments in mice have demonstrated that activation of NKT cells in vivo induces the expression of multiple effector molecules critical to successful immunity. Human clinical trials have shown similar responses, although in vivo activation of NKT cells in humans or primate models are far more limited in number and scope. Measuring ex vivo activation of NKT cells by the CD1d-restricted glycolipid ligand α-Galactosylceramide (α-GalCer) through cytokine expression profiles is a useful marker of NKT cell function, but for reasons that are unclear, this approach does not appear to work as well in humans and non-human primate macaque models in comparison to mice. We performed a series of experiments on human and macaque (Macaca nemestrina) fresh whole blood samples to define optimal conditions to detect NKT cell cytokine (TNF, IFNγ, IL-2) and degranulation marker (CD107a) expression by flow cytometry. We found that conditions previously described for mouse splenocyte NKT cell activation were suboptimal on human or macaque blood NKT cells. In contrast, a 6h incubation with brefeldin A added for the last 4h, in a 96-well plate based assay, and using an α-GalCer concentration of 1 μg/ml were optimal methods to stimulate NKT cells in fresh blood from both humans and macaques. Unexpectedly, we noted that blood NKT cells from macaques infected with SIV were more readily activated by α-GalCer than NKT cells from uninfected macaques, suggesting that SIV infection may have primed the NKT cells. In conclusion, we describe optimized methods for the ex vivo antigen-specific activation of human and macaque blood NKT cells. These assays should be useful in monitoring NKT cells in disease and in immunotherapy studies. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Cyto- and receptor architecture of area 32 in human and macaque brains.

    Science.gov (United States)

    Palomero-Gallagher, Nicola; Zilles, Karl; Schleicher, Axel; Vogt, Brent A

    2013-10-01

    Human area 32 plays crucial roles in emotion and memory consolidation. It has subgenual (s32), pregenual (p32), dorsal, and midcingulate components. We seek to determine whether macaque area 32 has subgenual and pregenual subdivisions and the extent to which they are comparable to those in humans by means of NeuN immunohistochemistry and multireceptor analysis of laminar profiles. The macaque has areas s32 and p32. In s32, layer IIIa/b neurons are larger than those of layer IIIc. This relationship is reversed in p32. Layer Va is thicker and Vb thinner in s32. Area p32 contains higher kainate, benzodiazepine (BZ), and serotonin (5-HT)1A but lower N-methyl-D-aspartate (NMDA) and α2 receptor densities. Most differences were found in layers I, II, and VI. Together, these differences support the dual nature of macaque area 32. Comparative analysis of human and macaque s32 and p32 supports equivalences in cyto- and receptor architecture. Although there are differences in mean areal receptor densities, there are considerable similarities at the layer level. Laminar receptor distribution patterns in each area are comparable in the two species in layers III-Va for kainate, NMDA, γ-aminobutyric acid (GABA)B , BZ, and 5-HT1A receptors. Multivariate statistical analysis of laminar receptor densities revealed that human s32 is more similar to macaque s32 and p32 than to human p32. Thus, macaque 32 is more complex than hitherto known. Our data suggest a homologous neural architecture in anterior cingulate s32 and p32 in human and macaque brains. © 2013 Wiley Periodicals, Inc.

  19. Susceptibility of Meningococcal Strains Responsible for Two Serogroup B Outbreaks on U.S. University Campuses to Serum Bactericidal Activity Elicited by the MenB-4C Vaccine.

    Science.gov (United States)

    Rossi, Raffaella; Beernink, Peter T; Giuntini, Serena; Granoff, Dan M

    2015-12-01

    In 2013 and 2014, two U.S. universities had meningococcal serogroup B outbreaks (a total of 14 cases) caused by strains from two different clonal complexes. To control the outbreaks, students were immunized with a serogroup B meningococcal vaccine (Novartis) that was not yet licensed in the United States. The vaccine (referred to as MenB-4C) contains four components capable of eliciting bactericidal activity. Both outbreak strains had high expression levels of two of the vaccine antigens (subfamily B factor H binding protein [FHbp] and neisserial heparin binding antigen [NHba]); the university B outbreak strain also had moderate expression of a third antigen, NadA. We investigated the bactericidal activity of sera from mice immunized with FHbp, NHba, or NadA and sera from MenB-4C-immunized infant macaques and an adult human. The postimmunization bactericidal activity of the macaque or human serum against isolates from university B with FHbp identification (ID) 1 that exactly matched the vaccine FHbp sequence variant was 8- to 21-fold higher than that against isolates from university A with FHbp ID 276 (96% identity to the vaccine antigen). Based on the bactericidal activity of mouse antisera to FHbp, NadA, or NHba and macaque or human postimmunization serum that had been depleted of anti-FHbp antibody, the bactericidal activity against both outbreak strains largely or entirely resulted from antibodies to FHbp. Thus, despite the high level of strain expression of FHbp from a subfamily that matched the vaccine antigen, there can be large differences in anti-FHbp bactericidal activity induced by MenB-4C vaccination. Further, strains with moderate to high NadA and/or NHba expression can be resistant to anti-NadA or anti-NHba bactericidal activity elicited by MenB-4C vaccination. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform.

    Science.gov (United States)

    Gabitzsch, Elizabeth S; Balint-Junior, Joseph P; Xu, Younong; Balcaitis, Stephanie; Sanders-Beer, Brigitte; Karl, Julie; Weinhold, Kent J; Paessler, Slobodan; Jones, Frank R

    2012-11-26

    Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (Pnow hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Dried influenza vaccines : Over the counter vaccines

    NARCIS (Netherlands)

    Saluja, Vinay; Hinrichs, Wouter L. J.; Frijlink, Henderik W.

    2010-01-01

    Since last year influenza pandemic has struck again after 40 years, this is the right moment to discuss the different available formulation options for influenza vaccine. Looking back to the last 4 decades, most vaccines are still formulated as liquid solution. These vaccines have shown a poor

  2. Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque.

    Science.gov (United States)

    Soares, David; Goldrick, Isabelle; Lemon, Roger N; Kraskov, Alexander; Greensmith, Linda; Kalmar, Bernadett

    2017-06-15

    There are substantial differences across species in the organization and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration "thin" spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the Kv3.1b expression in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labeled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, and lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium, and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons. © 2017 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  3. Bipedal locomotion of bonnet macaques after spinal cord injury.

    Science.gov (United States)

    Babu, Rangasamy Suresh; Anand, P; Jeraud, Mathew; Periasamy, P; Namasivayam, A

    2007-10-01

    Experimental studies concerning the analysis of locomotor behavior in spinal cord injury research are widely performed in rodent models. The purpose of this study was to quantitatively evaluate the degree of functional recovery in reflex components and bipedal locomotor behavior of bonnet macaques (Macaca radiata) after spinal contusive injury. Six monkeys were tested for various reflex components (grasping, righting, hopping, extension withdrawal) and were trained preoperatively to walk in bipedal fashion on the simple and complex locomotor runways (narrow beam, grid, inclined plane, treadmill) of this investigation. The overall performance of the animals'motor behavior and the functional status of limb movements during bipedal locomotion were graded by the Combined Behavioral Score (CBS) system. Using the simple Allen weight-drop technique, a contusive injury was produced by dropping a 13-g weight from a height of 30 cm to the exposed spinal cord at the T12-L1 vertebral level of the trained monkeys. All the monkeys showed significant impairments in every reflex activity and in walking behavior during the early part of the postoperative period. In subsequent periods, the animals displayed mild alterations in certain reflex responses, such as grasping, extension withdrawal, and placing reflexes, which persisted through a 1-year follow-up. The contused animals traversed locomotor runways--narrow beam, incline plane, and grid runways--with more steps and few errors, as evaluated with the CBS system. Eventually, the behavioral performance of all spinal-contused monkeys recovered to near-preoperative level by the fifth postoperative month. The findings of this study reveal the recovery time course of various reflex components and bipedal locomotor behavior of spinal-contused macaques on runways for a postoperative period of up to 1 year. Our spinal cord research in primates is advantageous in understanding the characteristics of hind limb functions only, which possibly

  4. Turnover rates of B cells, T cells, and NK cells in simian immunodeficiency virus-infected and uninfected rhesus macaques

    NARCIS (Netherlands)

    Boer, R.J. de; Mohri, H.; Ho, D.D.; Perelson, A.S.

    2003-01-01

    We determined average cellular turnover rates by fitting mathematical models to 5-bromo-2'-deoxyuridine measurements in SIV-infected and uninfected rhesus macaques. The daily turnover rates of CD4(+) T cells, CD4(-) T cells, CD20(+) B cells, and CD16(+) NK cells in normal uninfected rhesus macaques

  5. Serotonin transporter genotype modulates social reward and punishment in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Karli K Watson

    Full Text Available Serotonin signaling influences social behavior in both human and nonhuman primates. In humans, variation upstream of the promoter region of the serotonin transporter gene (5-HTTLPR has recently been shown to influence both behavioral measures of social anxiety and amygdala response to social threats. Here we show that length polymorphisms in 5-HTTLPR predict social reward and punishment in rhesus macaques, a species in which 5-HTTLPR variation is analogous to that of humans.In contrast to monkeys with two copies of the long allele (L/L, monkeys with one copy of the short allele of this gene (S/L spent less time gazing at face than non-face images, less time looking in the eye region of faces, and had larger pupil diameters when gazing at photos of a high versus low status male macaques. Moreover, in a novel primed gambling task, presentation of photos of high status male macaques promoted risk-aversion in S/L monkeys but promoted risk-seeking in L/L monkeys. Finally, as measured by a "pay-per-view" task, S/L monkeys required juice payment to view photos of high status males, whereas L/L monkeys sacrificed fluid to see the same photos.These data indicate that genetic variation in serotonin function contributes to social reward and punishment in rhesus macaques, and thus shapes social behavior in humans and rhesus macaques alike.

  6. Survey of prevalence of overweight body condition in laboratory-housed cynomolgus macaques (Macaca fascicularis).

    Science.gov (United States)

    Bauer, Sharon A; Leslie, Ken E; Pearl, David L; Fournier, Jocelyn; Turner, Patricia V

    2010-07-01

    Excessive weight gain has been reported to occur in captive cynomolgus macaques with little to no change in diet. Overweight body condition can result in development of hyperglycemia and type 2 diabetes and should be avoided. The purpose of this survey was to assess the prevalence of overweight cynomolgus macaques in North American research facilities, including breeding colonies and short-term and long-term facilities, and to describe current methods used to assess body condition. The survey consisted of 51 questions covering animal population demographics, body weight and body condition scoring, feeding, and behavior. Voluntary participants included veterinarians and animal care managers. Respondents from 13 facilities completed the survey, and information was collected on 17,500 cynomolgus macaques. The majority of surveyed facilities housed juvenile and young adult macaques. The reported prevalence of overweight (greater than 10% of ideal body weight) animals ranged between 0% and 20% and reportedly was more frequent in animals younger than 10 y. Most facilities had weight reduction strategies in place. Despite these programs, a significant proportion of animals were reported as being overweight. The results of this survey demonstrate that most North American facilities housing cynomolgus macaques recognize the importance of tracking body condition regularly. However, implementing effective weight reduction programs may be difficult in captive housing environments. Because of the potential for adverse health effects, facilities should have a means of regularly tracking body weight as well as an action plan for managing overweight animals.

  7. The genetic composition of populations of cynomolgus macaques (Macaca fascicularis) used in biomedical research.

    Science.gov (United States)

    Kanthaswamy, S; Ng, J; Satkoski Trask, J; George, D A; Kou, A J; Hoffman, L N; Doherty, T B; Houghton, P; Smith, D G

    2013-06-01

    The genetic composition of cynomolgus macaques used in biomedical research is not as well-characterized as that of rhesus macaques. Populations of cynomolgus macaques from Sumatra, Corregidor, Mauritius, Singapore, Cambodia, and Zamboanga were analyzed using 24 STRs. The Sumatran and Cambodian populations exhibited the highest allelic diversity, while the Mauritian population exhibited the lowest. Sumatran cynomolgus macaques were the most genetically similar to all others, consistent with an Indonesian origin of the species. The high diversity among Cambodian animals may result from interbreeding with rhesus macaques. The Philippine and Mauritian samples were the most divergent from other populations, the former due to separation from the Sunda Shelf by deepwater and the latter due to anthropogenic translocation and extreme founder effects. Investigators should verify their research subjects' origin, ancestry, and pedigree to minimize risks to biomedical experimentation from genetic variance stemming from close kinship and mixed ancestry as these can obscure treatment effects. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity.

    Directory of Open Access Journals (Sweden)

    Laura M J Ylinen

    2010-08-01

    Full Text Available TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5alpha but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations.

  9. Live attenuated Francisella novicida vaccine protects against Francisella tularensis pulmonary challenge in rats and non-human primates.

    Directory of Open Access Journals (Sweden)

    Ping Chu

    2014-10-01

    Full Text Available Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt, leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP. The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.

  10. Vaccines and Pregnancy

    Science.gov (United States)

    ... high or when infection would pose a high risk to the mother or baby, vaccination with a live vaccine is discussed. If there ... and benefits. For some diseases the benefit of vaccination outweighs any risks that may be associated with the vaccine. What ...

  11. History of vaccination.

    Science.gov (United States)

    Plotkin, Stanley

    2014-08-26

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

  12. History of vaccination

    OpenAIRE

    Plotkin, Stanley

    2014-01-01

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

  13. A Single Amino Acid Change in the Marburg Virus Glycoprotein Arises during Serial Cell Culture Passages and Attenuates the Virus in a Macaque Model of Disease.

    Science.gov (United States)

    Alfson, Kendra J; Avena, Laura E; Delgado, Jenny; Beadles, Michael W; Patterson, Jean L; Carrion, Ricardo; Griffiths, Anthony

    2018-01-01

    Marburg virus (MARV) causes disease with high case fatality rates, and there are no approved vaccines or therapies. Licensing of MARV countermeasures will likely require approval via the FDA's Animal Efficacy Rule, which requires well-characterized animal models that recapitulate human disease. This includes selection of the virus used for exposure and ensuring that it retains the properties of the original isolate. The consequences of amplification of MARV for challenge studies are unknown. Here, we serially passaged and characterized MARV through 13 passes from the original isolate. Surprisingly, the viral genome was very stable, except for a single nucleotide change that resulted in an amino acid substitution in the hydrophobic region of the signal peptide of the glycoprotein (GP). The particle/PFU ratio also decreased following passages, suggesting a role for the amino acid in viral infectivity. To determine if amplification introduces a phenotype in an animal model, cynomolgus macaques were exposed to either 100 or 0.01 PFU of low- and high-passage-number MARV. All animals succumbed when exposed to 100 PFU of either passage 3 or 13 viruses, although animals exposed to the high-passage-number virus survived longer. However, none of the passage 13 MARV-exposed animals succumbed to 0.01-PFU exposure compared to 75% of passage 3-exposed animals. This is consistent with other filovirus studies that show some particles that are unable to yield a plaque in cell culture can cause lethal disease in vivo . These results have important consequences for the design of experiments that investigate MARV pathogenesis and that test the efficacy of MARV countermeasures. IMPORTANCE Marburg virus (MARV) causes disease with a high case fatality rate, and there are no approved vaccines or therapies. Serial amplification of viruses in cell culture often results in accumulation of mutations, but the effect of such cell culture passage on MARV is unclear. Serial passages of MARV

  14. Mexico introduces pentavalent vaccine.

    Science.gov (United States)

    1999-08-01

    Combination vaccines have been introduced in Mexico. The national immunization program has incorporated the measles-mumps-rubella (MMR) vaccines in 1998, and the pentavalent vaccine in 1999. The two categories of antigen composition in combination vaccines are: 1) multiple different antigenic types of a single pathogen, such as the 23 valent pneumococcal polysaccharide vaccine, and 2) antigens from different pathogens causing different diseases, such as the DPT and MMR vaccines. Pentavalent vaccines are included in the second category. The vaccine protects against diphtheria, tetanus, pertussis, hepatitis B, and other diseases produced by Haemophilus influenzae type b (Hib). Combined diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenza type b (DTP-HB/Hib) vaccine has been distributed to 87% of Mexican children under 1 year of age. Over 800,000 doses of pentavalent vaccine have been administered.

  15. Attention and normalization circuits in macaque V1

    Science.gov (United States)

    Sanayei, M; Herrero, J L; Distler, C; Thiele, A

    2015-01-01

    Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms. PMID:25757941

  16. Macaque accessory optic system: II. Connections with the pretectum

    International Nuclear Information System (INIS)

    Baleydier, C.; Magnin, M.; Cooper, H.M.

    1990-01-01

    Connections of the accessory optic system (AOS) with the pretectum are described in the macaque monkey. Injections of tritiated amino acids in the pretectum demonstrate a major contralateral projection to the dorsal (DTN), lateral (LTN), and medial (MTN) terminal nuclei of the AOS and a sparser projection to the ipsilateral LTN. Injections of retrograde tracers, Fast Blue (FB), or wheat germ agglutinin horseradish peroxidase (WGA-HRP) plus nonconjugated horseradish peroxidase (HRP) in the LTN show that the pretectal-LTN projection originates from two nuclei. The main source of pretectal efferents to the LTN is from the pretectal olivary nucleus (OPN) and is entirely contralateral. This projection, which appears unique to primates, originates from the large multipolar cells of the OPN. In addition to this projection, the nucleus of the optic tract (NOT) projects to the ipsilateral LTN, as in nonprimates. Injection of WGA-HRP in the pretectum shows a reciprocal predominantely ipsilateral projection from the LTN to the pretectum. Retinas were observed after injection of FB in the LTN. The retinal ganglion cells projecting to the AOS are mainly distributed near the fovea and in the nasal region of the contralateral eye, suggesting a nasotemporal pattern of decussation. The demonstration of a direct connection between LTN and OPN forces to a reconsideration of the functional role of the AOS. Previous descriptions of luminance responsive cells in the LTN support a possible participation of this nucleus in the control of the pupillary light reflex

  17. Economic choices reveal probability distortion in macaque monkeys.

    Science.gov (United States)

    Stauffer, William R; Lak, Armin; Bossaerts, Peter; Schultz, Wolfram

    2015-02-18

    Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing. Copyright © 2015 Stauffer et al.

  18. Attention and normalization circuits in macaque V1.

    Science.gov (United States)

    Sanayei, M; Herrero, J L; Distler, C; Thiele, A

    2015-04-01

    Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. Distress prevention by grooming others in crested black macaques.

    Science.gov (United States)

    Aureli, Filippo; Yates, Kerrie

    2010-02-23

    Allogrooming is probably one of the most common and most studied social behaviours in a variety of animals. Whereas the short-term benefits for the groomee have often been investigated, little is known about the effects for the groomer. Our study focused on the short-term effects of grooming another group member in seven adult female crested black macaques (Macaca nigra). We found reductions in self-directed behaviour, an indicator of anxiety, and aggressive tendencies soon after grooming, when compared to matched-control periods. These findings can be interpreted as evidence of distress prevention, possibly mediated by an increase in tolerance. Indeed, a former groomee was more likely to be the nearest neighbour of the former groomer in the 10 min after grooming ended. Thus, the role of grooming in short-term distress alleviation can be applicable to the groomer as well as the groomee. These short-term effects, together with the longer-term effects of large and/or strong grooming networks confirm that grooming, as well as receiving grooming, has great importance for social dynamics.

  20. Vaccines today, vaccines tomorrow: a perspective.

    Science.gov (United States)

    Loucq, Christian

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts.

  1. Oral vaccination of fish

    OpenAIRE

    Embregts, Carmen W.E.; Forlenza, Maria

    2016-01-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines fo...

  2. Points to consider in the development of a surrogate for efficacy of novel Japanese encephalitis virus vaccines.

    Science.gov (United States)

    Markoff, L

    2000-05-26

    Although an effective killed virus vaccine to prevent illness due to Japanese encephalitis virus (JEV) infection exists, many authorities recognize that a safe, effective live JEV vaccine is desirable in order to reduce the cost and the number of doses of vaccine required per immunization. A large-scale clinical efficacy trail for such a vaccine would be both unethical and impractical. Therefore, a surrogate for the efficacy of JE vaccines should be established. Detection of virus-neutralizing antibodies in sera of vaccinees could constitute such a surrogate for efficacy. Field studies of vaccinees in endemic areas and studies done in mice already exist to support this concept. Also, titers of virus-neutralizing antibodies are already accepted as a surrogate for the efficacy of yellow fever virus vaccines and for the efficacy of other viral vaccines as well. In developing a correlation between N antibody titers and protection from JEV infection, standard procedures must be validated and adopted for both measuring N antibodies and for testing in animals. A novel live virus vaccine could be tested in the mouse and/or the monkey model of JEV infection to establish a correlation between virus-neutralizing antibodies elicited by the vaccines and protection from encephalitis. In addition, sera of subjects receiving the novel live JEV vaccine in early clinical trials could be passively transferred to mice or monkeys in order to establish the protective immunogenicity of the vaccine in humans. A monkey model for JEV infection was recently established by scientists at WRAIR in the US. From this group, pools of JEV of known infectivity for Rhesus macaques may be obtained for testing of immunity elicited by live JE vaccine virus.

  3. Recombinant vesicular stomatitis virus vaccine vectors expressing filovirus glycoproteins lack neurovirulence in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Chad E Mire

    Full Text Available The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV that expresses an individual filovirus glycoprotein (GP in place of the VSV glycoprotein (G. The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV GP; three animals received rVSV-wild type (wt vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use.

  4. A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage.

    Science.gov (United States)

    Shan, Chao; Muruato, Antonio E; Jagger, Brett W; Richner, Justin; Nunes, Bruno T D; Medeiros, Daniele B A; Xie, Xuping; Nunes, Jannyce G C; Morabito, Kaitlyn M; Kong, Wing-Pui; Pierson, Theodore C; Barrett, Alan D; Weaver, Scott C; Rossi, Shannan L; Vasconcelos, Pedro F C; Graham, Barney S; Diamond, Michael S; Shi, Pei-Yong

    2017-09-22

    Zika virus infection during pregnancy can cause congenital abnormities or fetal demise. The persistence of Zika virus in the male reproductive system poses a risk of sexual transmission. Here we demonstrate that live-attenuated Zika virus vaccine candidates containing deletions in the 3' untranslated region of the Zika virus genome (ZIKV-3'UTR-LAV) prevent viral transmission during pregnancy and testis damage in mice, as well as infection of nonhuman primates. After a single-dose vaccination, pregnant mice challenged with Zika virus at embryonic day 6 and evaluated at embryonic day 13 show markedly diminished levels of viral RNA in maternal, placental, and fetal tissues. Vaccinated male mice challenged with Zika virus were protected against testis infection, injury, and oligospermia. A single immunization of rhesus macaques elicited a rapid and robust antibody response, conferring complete protection upon challenge. Furthermore, the ZIKV-3'UTR-LAV vaccine candidates have a desirable safety profile. These results suggest that further development of ZIKV-3'UTR-LAV is warranted for humans.Zika virus infection can result in congenital disorders and cause disease in adults, and there is currently no approved vaccine. Here Shan et al. show that a single dose of a live-attenuated Zika vaccine prevents infection, testis damage and transmission to the fetus during pregnancy in different animal models.

  5. Mixed-complexity artificial grammar learning in humans and macaque monkeys: evaluating learning strategies.

    Science.gov (United States)

    Wilson, Benjamin; Smith, Kenny; Petkov, Christopher I

    2015-03-01

    Artificial grammars (AG) can be used to generate rule-based sequences of stimuli. Some of these can be used to investigate sequence-processing computations in non-human animals that might be related to, but not unique to, human language. Previous AG learning studies in non-human animals have used different AGs to separately test for specific sequence-processing abilities. However, given that natural language and certain animal communication systems (in particular, song) have multiple levels of complexity, mixed-complexity AGs are needed to simultaneously evaluate sensitivity to the different features of the AG. Here, we tested humans and Rhesus macaques using a mixed-complexity auditory AG, containing both adjacent (local) and non-adjacent (longer-distance) relationships. Following exposure to exemplary sequences generated by the AG, humans and macaques were individually tested with sequences that were either consistent with the AG or violated specific adjacent or non-adjacent relationships. We observed a considerable level of cross-species correspondence in the sensitivity of both humans and macaques to the adjacent AG relationships and to the statistical properties of the sequences. We found no significant sensitivity to the non-adjacent AG relationships in the macaques. A subset of humans was sensitive to this non-adjacent relationship, revealing interesting between- and within-species differences in AG learning strategies. The results suggest that humans and macaques are largely comparably sensitive to the adjacent AG relationships and their statistical properties. However, in the presence of multiple cues to grammaticality, the non-adjacent relationships are less salient to the macaques and many of the humans. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  6. Impact of menstruation on select hematology and clinical chemistry variables in cynomolgus macaques.

    Science.gov (United States)

    Perigard, Christopher J; Parrula, M Cecilia M; Larkin, Matthew H; Gleason, Carol R

    2016-06-01

    In preclinical studies with cynomolgus macaques, it is common to have one or more females presenting with menses. Published literature indicates that the blood lost during menses causes decreases in red blood cell mass variables (RBC, HGB, and HCT), which would be a confounding factor in the interpretation of drug-related effects on clinical pathology data, but no scientific data have been published to support this claim. This investigation was conducted to determine if the amount of blood lost during menses in cynomolgus macaques has an effect on routine hematology and serum chemistry variables. Ten female cynomolgus macaques (Macaca fascicularis), 5 to 6.5 years old, were observed daily during approximately 3 months (97 days) for the presence of menses. Hematology and serum chemistry variables were evaluated twice weekly. The results indicated that menstruation affects the erythrogram including RBC, HGB, HCT, MCHC, MCV, reticulocyte count, RDW, the leukogram including neutrophil, lymphocyte, and monocyte counts, and chemistry variables, including GGT activity, and the concentrations of total proteins, albumin, globulins, and calcium. The magnitude of the effect of menstruation on susceptible variables is dependent on the duration of the menstrual phase. Macaques with menstrual phases lasting ≥ 7 days are more likely to develop changes in variables related to chronic blood loss. In preclinical toxicology studies with cynomolgus macaques, interpretation of changes in several commonly evaluated hematology and serum chemistry variables requires adequate clinical observation and documentation concerning presence and duration of menses. There is a concern that macaques with long menstrual cycles can develop iron deficiency anemia due to chronic menstrual blood loss. © 2016 American Society for Veterinary Clinical Pathology.

  7. Laboratory rhesus macaque social housing and social changes: Implications for research.

    Science.gov (United States)

    Hannibal, Darcy L; Bliss-Moreau, Eliza; Vandeleest, Jessica; McCowan, Brenda; Capitanio, John

    2017-01-01

    Macaque species, specifically rhesus (Macaca mulatta), are the most common nonhuman primates (NHPs) used in biomedical research due to their suitability as a model of high priority diseases (e.g., HIV, obesity, cognitive aging), cost effective breeding and housing compared to most other NHPs, and close evolutionary relationship to humans. With this close evolutionary relationship, however, is a shared adaptation for a socially stimulating environment, without which both their welfare and suitability as a research model are compromised. While outdoor social group housing provides the best approximation of a social environment that matches the macaque behavioral biology in the wild, this is not always possible at all facilities, where animals may be housed indoors in small groups, in pairs, or alone. Further, animals may experience many housing changes in their lifetime depending on project needs, changes in social status, management needs, or health concerns. Here, we review the evidence for the physiological and health effects of social housing changes and the potential impacts on research outcomes for studies using macaques, particularly rhesus. We situate our review in the context of increasing regulatory pressure for research facilities to both house NHPs socially and mitigate trauma from social aggression. To meet these regulatory requirements and further refine the macaque model for research, significant advances must be made in our understanding and management of rhesus macaque social housing, particularly pair-housing since it is the most common social housing configuration for macaques while on research projects. Because most NHPs are adapted for sociality, a social context is likely important for improving repeatability, reproducibility, and external validity of primate biomedical research. Am. J. Primatol. 79:e22528, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Grooming-related feeding motivates macaques to groom and affects grooming reciprocity and episode duration in Japanese macaques (Macaca fuscata).

    Science.gov (United States)

    Onishi, Kenji; Yamada, Kazunori; Nakamichi, Masayuki

    2013-01-01

    Allogrooming is considered as an altruistic behavior wherein primates exchange grooming as a tradable commodity for reciprocal grooming or other commodities such as support during aggression and tolerance during co-feeding. First, we report a case of the grooming relationships of the lowest-ranking adult female in a group of Japanese macaques (Macaca fuscata). The female (Lp) had lost a portion of the fur and was groomed by higher-ranking individuals without providing reciprocal grooming or other commodities. The groomers probably fed on lice eggs from the fur of Lp more frequently than from that of other adult groomees. This suggests that grooming-related feeding (GRF) motivated many individuals to groom Lp and influenced grooming reciprocity in dyads. Second, we investigated quantitative grooming data for adult females. A high GRF rate was found to lengthen the duration of grooming, suggesting that GRF motivates groomers to groom. From these results, we proposed 2 possible reasons for groomers' sensitivity to GRF rate: (1) the nutritional benefit from GRF compensates for part of the cost of giving grooming and facilitates giving grooming and (2) groomer's sensitivity to the GRF rate maintains the efficiency of removing lice eggs and ensures the groomee's hygienic benefit in receiving grooming. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Typhoid fever vaccination strategies.

    Science.gov (United States)

    Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley

    2015-06-19

    Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control. Copyright © 2015. Published by

  10. Differences in time of virus appearance in the blood and virus-specific immune responses in intravenous and intrarectal primary SIVmac251 infection of rhesus macaques; a pilot study

    Directory of Open Access Journals (Sweden)

    Washington Parks Robyn

    2001-07-01

    Full Text Available Abstract Background HIV-I can be transmitted by intravenous inoculation of contaminated blood or blood product or sexually through mucosal surfaces. Here we performed a pilot study in the SIVmac251 macaque model to address whether the route of viral entry influences the kinetics of the appearance and the size of virus-specific immune in different tissue compartments. Methods For this purpose, of 2 genetically defined Mamu-A*01-positive macaques, 1 was exposed intravenously and the other intrarectally to the same SIVmac251 viral stock and virus-specific CD8+ T-cells were measured within the first 12 days of infection in the blood and at day 12 in several tissues following euthanasia. Results Virus-specific CD8+ T-cell responses to Gag, Env, and particularly Tat appeared earlier in the blood of the animal exposed by the mucosal route than in the animal exposed intravenously. The magnitude of these virus-specific responses was consistently higher in the systemic tissues and GALT of the macaque exposed by the intravenous route, suggesting a higher viral burden in the tissues as reflected by the faster appearance of virus in plasma. Differences in the ability of the virus-specific CD8+ T-cells to respond in vitro to specific peptide stimulation were also observed and the greatest proliferative ability was found in the GALT of the animal infected by the intrarectal route. Conclusions These data may suggest that the natural mucosal barrier may delay viral spreading. The consequences of this observation, if confirmed in studies with a larger number of animals, may have implications in vaccine development.

  11. Vaccines: an ongoing promise?

    Science.gov (United States)

    Alsahli, M; Farrell, R J; Michetti, P

    2001-01-01

    Over the past decade, intensive research has focused on developing a vaccine therapy for Helicobacter pylori. Substantial unresolved questions cloud the current approach, and the development of a vaccine against this unique organism has proved very challenging. Many candidate vaccines have been tested in animal models. The immunogenicity and the safety of some vaccine formulations have been recently evaluated through clinical trials, and the efficacy of these vaccine therapies in humans will be determined in the near future. This article will provide an overview of the current knowledge of natural and vaccine-induced immune responses to H. pylori infection. It will also review past vaccine successes and failures in animal models and the limited experience to date in using vaccine therapy in humans. Several obstacles to H. pylori vaccine development efforts along with the future direction of these efforts will be discussed. Copyright 2001 S. Karger AG, Basel

  12. Neurologic complications of vaccinations.

    Science.gov (United States)

    Miravalle, Augusto A; Schreiner, Teri

    2014-01-01

    This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination. © 2014 Elsevier B.V. All rights reserved.

  13. Current Vaccine Shortages and Delays

    Science.gov (United States)

    ... Hepatitis A vaccine supply in the US. Updated Mar 2018 Note 2 : Pediatric hepatitis B vaccine: Merck ... Submitted, Licensed, and Recommended Vaccines & Biologics Red Book® Online Influenza Vaccination Recommendations Childhood & Adolescent Immunization Schedules Adult ...

  14. Vaccine-Preventable Disease Photos

    Science.gov (United States)

    ... Work Importance of Vaccines Paying for Vaccines State Immunization Programs Tips for Finding Vaccine Records Trusted Sources of ... efficacy, and use of vaccines within the broad immunization community of patients, parents, healthcare organizations, and government health agencies.

  15. Vaccines against poverty

    Science.gov (United States)

    MacLennan, Calman A.; Saul, Allan

    2014-01-01

    With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented. PMID:25136089

  16. Crossmodal integration of conspecific vocalizations in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Christa Payne

    Full Text Available Crossmodal integration of audio/visual information is vital for recognition, interpretation and appropriate reaction to social signals. Here we examined how rhesus macaques process bimodal species-specific vocalizations by eye tracking, using an unconstrained preferential looking paradigm. Six adult rhesus monkeys (3M, 3F were presented two side-by-side videos of unknown male conspecifics emitting different vocalizations, accompanied by the audio signal corresponding to one of the videos. The percentage of time animals looked to each video was used to assess crossmodal integration ability and the percentages of time spent looking at each of the six a priori ROIs (eyes, mouth, and rest of each video were used to characterize scanning patterns. Animals looked more to the congruent video, confirming reports that rhesus monkeys spontaneously integrate conspecific vocalizations. Scanning patterns showed that monkeys preferentially attended to the eyes and mouth of the stimuli, with subtle differences between males and females such that females showed a tendency to differentiate the eye and mouth regions more than males. These results were similar to studies in humans indicating that when asked to assess emotion-related aspects of visual speech, people preferentially attend to the eyes. Thus, the tendency for female monkeys to show a greater differentiation between the eye and mouth regions than males may indicate that female monkeys were slightly more sensitive to the socio-emotional content of complex signals than male monkeys. The current results emphasize the importance of considering both the sex of the observer and individual variability in passive viewing behavior in nonhuman primate research.

  17. Functional organization of area V2 in the alert macaque.

    Science.gov (United States)

    Peterhans, E; von der Heydt, R

    1993-05-01

    We studied the relation between anatomical structure and functional properties of cells in area V2 of the macaque. Visual function was assessed in the alert animal during fixation of gaze. Recording sites were reconstructed with respect to cortical lamination and the cytochrome oxidase pattern. We measured orientation and direction selectivity, end-stopping, sensitivity to binocular disparity and ocular dominance, and determined more complex functions like sensitivity to anomalous contours and lines defined by coherent motion. Orientation selectivity was found in all parts of area V2, with high frequencies in the pale and thick stripes of the cytochrome oxidase pattern, and with lower frequency in the thin stripes. Representations of anomalous contours were found in the pale and thick stripes with similar frequencies, but generally not in the thin stripes, which have been thought to process colour. Lines defined by coherent motion were most frequently represented in the thick stripes; they were less frequent in the pale stripes, and (as with anomalous contours) were not found in the thin stripes. Sensitivity to binocular disparity was found in all types of stripes, but more frequently in the thick stripes, where the exclusively binocular neurons were also concentrated. By contrast, no segregation was found for direction selectivity and end-stopping. All neuronal properties were distributed evenly across cortical laminae. We conclude that mechanisms for figure-ground segregation involve the pale and the thick stripes of the cytochrome oxidase pattern, perhaps with greater emphasis on 'shape from motion' and 'stereoscopic depth' in the thick stripes, while more elementary neuronal properties are distributed almost evenly across the stripe pattern.

  18. A neural circuit covarying with social hierarchy in macaques.

    Science.gov (United States)

    Noonan, MaryAnn P; Sallet, Jerome; Mars, Rogier B; Neubert, Franz X; O'Reilly, Jill X; Andersson, Jesper L; Mitchell, Anna S; Bell, Andrew H; Miller, Karla L; Rushworth, Matthew F S

    2014-09-01

    Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI), which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI) data in 25 group-living macaques. First, a deformation-based morphometric (DBM) approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status.

  19. A neural circuit covarying with social hierarchy in macaques.

    Directory of Open Access Journals (Sweden)

    MaryAnn P Noonan

    2014-09-01

    Full Text Available Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI, which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI data in 25 group-living macaques. First, a deformation-based morphometric (DBM approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status.

  20. A Neural Circuit Covarying with Social Hierarchy in Macaques

    Science.gov (United States)

    Neubert, Franz X.; O'Reilly, Jill X.; Andersson, Jesper L.; Mitchell, Anna S.; Bell, Andrew H.; Miller, Karla L.; Rushworth, Matthew F. S.

    2014-01-01

    Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI), which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI) data in 25 group-living macaques. First, a deformation-based morphometric (DBM) approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status. PMID:25180883

  1. Polymorphisms of cytochrome P450 2B6 (CYP2B6) in cynomolgus and rhesus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Uehara, Shotaro; Yamazaki, Hiroshi

    2018-02-22

    Cytochrome P450 2B6 (CYP2B6) is an important drug-metabolizing enzyme and is expressed in liver. Although human CYP2B6 variants account for variable enzyme properties among individuals and populations, CYP2B6 genetic variants have not been investigated in cynomolgus macaques, widely used in drug metabolism studies. CYP2B6 was resequenced in 120 cynomolgus macaques and 23 rhesus macaques by direct sequencing. Twenty-three non-synonymous variants were found, of which 12 and 3 were unique to cynomolgus macaques and rhesus macaques, respectively. By functional characterization using the 14 variant proteins, 8 variants (V114I, R253C, M435I, V459M, L465P, C475S, R487C, and R487H) showed different rate (>1.5-fold) of testosterone 16β-hydroxylation to wild type. However, the four variants (M435I, L465P, C475S, and R487H) were analyzed in liver microsomes, and the catalytic rates were not substantially different from wild type. Macaque CYP2B6 was polymorphic, and the genotype could partly account for variable enzyme activities of macaque CYP2B6. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Human behavior and opportunities for parasite transmission in communities surrounding long-tailed macaque populations in Bali, Indonesia.

    Science.gov (United States)

    Lane-DeGraaf, Kelly E; Putra, I G A Arta; Wandia, I Nengah; Rompis, Aida; Hollocher, Hope; Fuentes, Agustin

    2014-02-01

    Spatial overlap and shared resources between humans and wildlife can exacerbate parasite transmission dynamics. In Bali, Indonesia, an agricultural-religious temple system provides sanctuaries for long-tailed macaques (Macaca fascicularis), concentrating them in areas in close proximity to humans. In this study, we interviewed individuals in communities surrounding 13 macaque populations about their willingness to participate in behaviors that would put them at risk of exposure to gastrointestinal parasites to understand if age, education level, or occupation are significant determinants of exposure behaviors. These exposure risk behaviors and attitudes include fear of macaques, direct contact with macaques, owning pet macaques, hunting and eating macaques, and overlapping water uses. We find that willingness to participate in exposure risk behaviors are correlated with an individual's occupation, age, and/or education level. We also found that because the actual risk of infection varies across populations, activities such as direct macaque contact and pet ownership, could be putting individuals at real risk in certain contexts. Thus, we show that human demographics and social structure can influence willingness to participate in behaviors putting them at increased risk for exposure to parasites. © 2013 Wiley Periodicals, Inc.

  3. Vaccine Associated Myocarditis

    Directory of Open Access Journals (Sweden)

    Johnson Francis

    2017-04-01

    Full Text Available Most of the cases of vaccine associated myocarditis have been following small pox vaccination. Reports have also been there after streptococcal pneumonia vaccine and influenza vaccine. In some cases, autoimmune/inflammatory syndrome induced by adjuvants (ASIA used in the vaccine have been implicated. Exclusion of other causes is very important in the diagnostic process, especially that of acute coronary syndrome. Management is similar to that of other etiologies of myocarditis. These rare instances of myocarditis should not preclude one from taking necessary immunization for vaccine preventable diseases.

  4. Vaccines and Immunization Practice.

    Science.gov (United States)

    Hogue, Michael D; Meador, Anna E

    2016-03-01

    Vaccines are among most cost-effective public health strategies. Despite effective vaccines for many bacterial and viral illnesses, tens of thousands of adults and hundreds of children die each year in the United States from vaccine-preventable diseases. Underutilization of vaccines requires rethinking the approach to incorporating vaccines into practice. Arguably, immunizations could be a part all health care encounters. Shared responsibility is paramount if deaths are to be reduced. This article reviews the available vaccines in the US market, as well as practice recommendations of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Vaccines today, vaccines tomorrow: a perspective

    OpenAIRE

    Loucq, Christian

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles M?rieux are known among experts only despite their contribution to global hea...

  6. Sequential priming with simian immunodeficiency virus (SIV) DNA vaccines, with or without encoded cytokines, and a replicating adenovirus-SIV recombinant followed by protein boosting does not control a pathogenic SIVmac251 mucosal challenge.

    Science.gov (United States)

    Demberg, Thorsten; Boyer, Jean D; Malkevich, Nina; Patterson, L Jean; Venzon, David; Summers, Ebonita L; Kalisz, Irene; Kalyanaraman, V S; Lee, Eun Mi; Weiner, David B; Robert-Guroff, Marjorie

    2008-11-01

    Previously, combination DNA/nonreplicating adenovirus (Ad)- or poxvirus-vectored vaccines have strongly protected against SHIV(89.6P), DNAs expressing cytokines have modulated immunity elicited by DNA vaccines, and replication-competent Ad-recombinant priming and protein boosting has strongly protected against simian immunodeficiency virus (SIV) challenge. Here we evaluated a vaccine strategy composed of these promising components. Seven rhesus macaques per group were primed twice with multigenic SIV plasmid DNA with or without interleukin-12 (IL-12) DNA or IL-15 DNA. After a multigenic replicating Ad-SIV immunization, all groups received two booster immunizations with SIV gp140 and SIV Nef protein. Four control macaques received control DNA plasmids, empty Ad vector, and adjuvant. All vaccine components were immunogenic, but the cytokine DNAs had little effect. Macaques that received IL-15-DNA exhibited higher peak anti-Nef titers, a more rapid anti-Nef anamnestic response postchallenge, and expanded CD8(CM) T cells 2 weeks postchallenge compared to the DNA-only group. Other immune responses were indistinguishable between groups. Overall, no protection against intrarectal challenge with SIV(mac251) was observed, although immunized non-Mamu-A*01 macaques as a group exhibited a statistically significant 1-log decline in acute viremia compared to non-Mamu-A*01 controls. Possible factors contributing to the poor outcome include administration of cytokine DNAs to sites different from the Ad recombinants (intramuscular and intratracheal, respectively), too few DNA priming immunizations, a suboptimal DNA delivery method, failure to ensure delivery of SIV and cytokine plasmids to the same cell, and instability and short half-life of the IL-15 component. Future experiments should address these issues to determine if this combination approach is able to control a virulent SIV challenge.

  7. A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates.

    Science.gov (United States)

    Sha, Jian; Kirtley, Michelle L; Klages, Curtis; Erova, Tatiana E; Telepnev, Maxim; Ponnusamy, Duraisamy; Fitts, Eric C; Baze, Wallace B; Sivasubramani, Satheesh K; Lawrence, William S; Patrikeev, Igor; Peel, Jennifer E; Andersson, Jourdan A; Kozlova, Elena V; Tiner, Bethany L; Peterson, Johnny W; McWilliams, David; Patel, Snehal; Rothe, Eric; Motin, Vladimir L; Chopra, Ashok K

    2016-07-01

    Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. Population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space.

    Science.gov (United States)

    Feng, Lei; Jeon, Tina; Yu, Qiaowen; Ouyang, Minhui; Peng, Qinmu; Mishra, Virendra; Pletikos, Mihovil; Sestan, Nenad; Miller, Michael I; Mori, Susumu; Hsiao, Steven; Liu, Shuwei; Huang, Hao

    2017-12-01

    Animal models of the rhesus macaque (Macaca mulatta), the most widely used nonhuman primate, have been irreplaceable in neurobiological studies. However, a population-averaged macaque brain diffusion tensor imaging (DTI) atlas, including comprehensive gray and white matter labeling as well as bony and facial landmarks guiding invasive experimental procedures, is not available. The macaque white matter tract pathways and microstructures have been rarely recorded. Here, we established a population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space incorporating bony and facial landmarks, and delineated microstructures and three-dimensional pathways of major white matter tracts in vivo MRI/DTI and ex vivo (postmortem) DTI of ten rhesus macaque brains were acquired. Single-subject macaque brain DTI template was obtained by transforming the postmortem high-resolution DTI data into in vivo space. Ex vivo DTI of ten macaque brains was then averaged in the in vivo single-subject template space to generate population-averaged macaque brain DTI atlas. The white matter tracts were traced with DTI-based tractography. One hundred and eighteen neural structures including all cortical gyri, white matter tracts and subcortical nuclei, were labeled manually on population-averaged DTI-derived maps. The in vivo microstructural metrics of fractional anisotropy, axial, radial and mean diffusivity of the traced white matter tracts were measured. Population-averaged digital atlas integrated into in vivo space can be used to label the experimental macaque brain automatically. Bony and facial landmarks will be available for guiding invasive procedures. The DTI metric measurements offer unique insights into heterogeneous microstructural profiles of different white matter tracts.

  9. A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge.

    Science.gov (United States)

    Andrews, Chasity D; Yueh, Yun Lan; Spreen, William R; St Bernard, Leslie; Boente-Carrera, Mar; Rodriguez, Kristina; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Ford, Susan; Mohri, Hiroshi; Cheng-Mayer, Cecilia; Hong, Zhi; Ho, David D; Markowitz, Martin

    2015-01-14

    Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. We examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera (depot medroxyprogesterone acetate), which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50 mg/kg) monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were fivefold lower on average in cervical tissues than in rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high-dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected six of eight female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for PrEP. Copyright © 2015, American Association for the Advancement of Science.

  10. Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates.

    Science.gov (United States)

    Ault, Alida; Tennant, Sharon M; Gorres, J Patrick; Eckhaus, Michael; Sandler, Netanya G; Roque, Annelys; Livio, Sofie; Bao, Saran; Foulds, Kathryn E; Kao, Shing-Fen; Roederer, Mario; Schmidlein, Patrick; Boyd, Mary Adetinuke; Pasetti, Marcela F; Douek, Daniel C; Estes, Jacob D; Nabel, Gary J; Levine, Myron M; Rao, Srinivas S

    2013-12-02

    Nontyphoidal Salmonella (NTS) serovars are a common cause of acute food-borne gastroenteritis worldwide and can cause invasive systemic disease in young infants, the elderly, and immunocompromised hosts, accompanied by high case fatality. Vaccination against invasive NTS disease is warranted where the disease incidence and mortality are high and multidrug resistance is prevalent, as in sub-Saharan Africa. Live-attenuated vaccines that mimic natural infection constitute one strategy to elicit protection. However, they must particularly be shown to be adequately attenuated for consideration of immunocompromised subjects. Accordingly, we examined the safety and tolerability of an oral live attenuated Salmonella typhimurium vaccine candidate, CVD 1921, in an established chronic simian immunodeficiency virus (SIV)-infected rhesus macaque model. We evaluated clinical parameters, histopathology, and measured differences in mucosal permeability to wild-type and vaccine strains. Compared to the wild-type S. typhimurium strain I77 in both SIV-infected and SIV-uninfected nonhuman primate hosts, this live-attenuated vaccine shows reduced shedding and systemic spread, exhibits limited pathological disease manifestations in the digestive tract, and induces low levels of cellular infiltration in tissues. Furthermore, wild-type S. typhimurium induces increased intestinal epithelial damage and permeability, with infiltration of neutrophils and macrophages in both SIV-infected and SIV-uninfected nonhuman primates compared to the vaccine strain. Based on shedding, systemic spread, and histopathology, the live-attenuated S. typhimurium strain CVD 1921 appears to be safe and well-tolerated in the nonhuman primate model, including chronically SIV-infected rhesus macaques. Copyright © 2013. Published by Elsevier Ltd.

  11. MMR Vaccine (Measles, Mumps, and Rubella)

    Science.gov (United States)

    Mumpsvax® Mumps Vaccine ... Biavax® II (as a combination product containing Mumps Vaccine, Rubella Vaccine) ... II (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine)

  12. What is a Preventive HIV Vaccine?

    Science.gov (United States)

    ... Entire Series Related Content AIDSource | Vaccine Research HIV Vaccines History of HIV Vaccine Research Need Help? Call 1- ... Entire Series Related Content AIDSource | Vaccine Research HIV Vaccines History of HIV Vaccine Research Need Help? Call 1- ...

  13. No costly prosociality among related long-tailed macaques (Macaca fascicularis).

    Science.gov (United States)

    Sterck, Elisabeth H M; Olesen, Caroline U; Massen, Jorg J M

    2015-08-01

    Altruism, benefiting another at a cost to the donor, may be achieved through prosocial behavior. Studies of nonhuman animals typically investigate prosocial behavior with paradigms in which the donor can choose to give a recipient a food item, and the choice does not affect the donor's reward (which is either present or absent). In such tasks, long-tailed macaques (Macaca fascicularis) show prosocial behavior, especially toward kin. Here, we tested captive long-tailed macaques with related recipients in an alternative task, in which the donor had to give up a preferred reward to benefit the recipient; that is, they had to choose a lower valued reward for themselves to provide food to their kin. Overall, the macaques did not provide their kin with food. The task forced the donor to balance its prosocial behavior with its selfish choice for a higher value reward, a balance that turned out to favor selfish motives. Consequently, our study shows that a prosocial tendency is not sufficient to elicit costly prosocial behavior in long-tailed macaques. Subsequently, we feel that tasks in which the donor must choose a lower value reward to benefit another individual may allow the titration of the strength of prosocial behavior, and thus provides interesting possibilities for future comparative studies. (c) 2015 APA, all rights reserved).

  14. Hair loss and hair-pulling in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Lutz, Corrine K; Coleman, Kristine; Worlein, Julie; Novak, Melinda A

    2013-07-01

    Alopecia is a common problem in rhesus macaque colonies. A possible cause of this condition is hair-pulling; however the true relationship between hair-pulling and alopecia is unknown. The purpose of this study was to examine the relationship between hair loss and hair-pulling in 1258 rhesus macaques housed in 4 primate colonies across the United States. Alopecia levels ranged from 34.3% to 86.5% (mean, 49.3%) at the primate facilities. At facilities reporting a sex-associated difference, more female macaques were reported to exhibit alopecia than were males. In contrast, more males were reported to hair-pull. Animals reported to hair-pull were significantly more likely to have some amount of alopecia, but rates of hair-pulling were substantially lower than rates of alopecia, ranging from 0.6% to 20.5% (mean, 7.7%) of the populations. These results further demonstrate that hair-pulling plays only a small role in alopecia in rhesus macaques.

  15. Effects of Transportation on Antioxidant Status in Cynomolgus Macaques (Macaca fascicularis).

    Science.gov (United States)

    Pan, Xueying; Lu, Liang; Zeng, Xiancheng; Chang, Yan; Hua, Xiuguo

    2016-01-01

    To evaluate the effects of transportation on oxidative stress in cynomolgus monkeys, we measured serum levels of reduced glutathione (GSH), malondialdehyde, and protein carbonyl (PC) and the activities of total antioxidant capacity (TAOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in cynomolgus macaques before transportation (day 0), on the day of arrival (day 1), and on days 7, 14, and 21 after transportation. Compared with that on day 0, TAOC and catalase activities on days 1, 7, and 14 after transportation were significantly decreased, reached their nadirs on day 7, and increased thereafter to reach their pretransportation levels by day 21 after transportation. Compared with day 0 levels, mean SOD activity and GSH concentration were decreased significantly on day 1; they thereafter increased to reach their pretransportation measures by day 7 after transportation. In contrast, PC and malondialdehyde concentrations in serum and the activity of GSH-Px were increased on day 1 compared with day 0 and thereafter decreased to reach their pretransportation levels by day 14 after transportation. In summary, GSH, TAOC, catalase, and SOD levels decreased and malondialdehyde, PC, and GSH-Px concentrations increased in cynomolgus macaques after transportation. These results suggest that transportation might imbalance oxidant and antioxidant levels to create excess oxidative stress in cynomolgus macaques. Therefore, cynomolgus macaques should have at least 21 d to recover after transportation and regain their healthy status.

  16. Pharmacokinetics of 2 Formulations of Transdermal Fentanyl in Cynomolgus Macaques (Macaca fascicularis)

    Science.gov (United States)

    Carlson, Amy M; Kelly, Richard; Fetterer, David P; Rico, Pedro J; Bailey, Emily J

    2016-01-01

    Fentanyl is a μ-opioid agonist that often is used as the analgesic component for balanced anesthesia in both human and veterinary patients. Minimal information has been published regarding appropriate dosing, and the pharmacokinetics of fentanyl are unknown in NHP. The pharmacokinetic properties of 2 transdermal fentanyl delivery methods, a solution (2.6 and 1.95 mg/kg) and a patch (25 µg/h), were determined when applied topically to the dorsal scapular area of cynomolgus macaques (Macaca fascicularis). Serum fentanyl concentrations were analyzed by using liquid chromatography–mass spectrometry. Compared with the patch, the transdermal fentanyl solution generated higher drug concentrations over longer time. Adverse reactions occurred in the macaques that received the transdermal fentanyl solution at 2.6 mg/kg. Both preparations showed significant interanimal variability in the maximal serum drug levels, time to achieve maximal fentanyl levels, elimination half-life, and AUC values. Both the maximal concentration and the time at which this concentration occurred were increased in macaques compared with most other species after application of the transdermal fentanyl patch and compared with dogs after application of the transdermal fentanyl solution. The pharmacokinetic properties of transdermal fentanyl in macaques are markedly different from those in other veterinary species and preclude its use as a long-acting analgesic drug in NHP. PMID:27423151

  17. Resource use of Japanese macaques in heavy snowfall areas: implications for habitat management.

    Science.gov (United States)

    Enari, Hiroto; Sakamaki-Enari, Haruka

    2013-07-01

    Populations of Japanese macaque (Macaca fuscata) that inhabit the northernmost distribution of any nonhuman primates have been listed as endangered in Japan; however, macaques are widely known for being pests that cause agricultural damage. This study identified priority areas for the conservation and management of macaque habitats, by comparing the resource use of troops occupying remote mountains (montane troops) against troops inhabiting disturbed forests adjacent to settlements (rural troops). We collected species presence data across 2 years by radio-tracking two montane troops and two rural troops in the Shirakami Mountains. We developed seasonal utilization distributions by using the kernel method, and identified habitat characteristics by using ecological-niche factor analysis (ENFA). Our results indicate that environmental factors influencing the potential habitat varied widely with season in montane troops as compared with that in rural troops. ENFA results demonstrated that rural troops exhibited more biased resource use and narrower niche breadths than montane troops. Based on our findings, we propose that (1) primary broadleaf forests are the spring habitat conservation priority of montane troops; (2) the habitat unit--the product of habitat suitability index and its surface area--for montane troops is enhanced by removing old conifer plantations from the forest edge at low elevations; (3) such removal around settlements may also contribute toward removing a frontline refuge for rural troops intruding farmlands; and (4) intensive prevention measures against macaque intrusions into settlements during the bottleneck snowy season contribute toward reducing the habitat unit of rural troops.

  18. A single gp120 residue can affect HIV-1 tropism in macaques.

    Directory of Open Access Journals (Sweden)

    Gregory Q Del Prete

    2017-09-01

    Full Text Available Species-dependent variation in proteins that aid or limit virus replication determines the ability of lentiviruses to jump between host species. Identifying and overcoming these differences facilitates the development of animal models for HIV-1, including models based on chimeric SIVs that express HIV-1 envelope (Env glycoproteins, (SHIVs and simian-tropic HIV-1 (stHIV strains. Here, we demonstrate that the inherently poor ability of most HIV-1 Env proteins to use macaque CD4 as a receptor is improved during adaptation by virus passage in macaques. We identify a single amino acid, A281, in HIV-1 Env that consistently changes during adaptation in macaques and affects the ability of HIV-1 Env to use macaque CD4. Importantly, mutations at A281 do not markedly affect HIV-1 Env neutralization properties. Our findings should facilitate the design of HIV-1 Env proteins for use in non-human primate models and thus expedite the development of clinically relevant reagents for testing interventions against HIV-1.

  19. Temporary hindlimb paresis following dystocia due to foetal macrosomia in a Celebes crested macaque (Macaca nigra).

    Science.gov (United States)

    Debenham, John James; Bettembourg, Vanessa; Østevik, Liv; Modig, Michaela; Jâderlund, Karin Hultin; Lervik, Andreas

    2017-04-01

    A multiparous Celebes crested macaque presented with dystocia due to foetal macrosomia, causing foetal mortality and hindlimb paresis. After emergency caesarean section, recovery of motor function took 1 month before hindlimbs were weight bearing and 2 months before re-integration with the troop. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Ranking network of a captive rhesus macaque society: a sophisticated corporative kingdom.

    Science.gov (United States)

    Fushing, Hsieh; McAssey, Michael P; Beisner, Brianne; McCowan, Brenda

    2011-03-15

    We develop a three-step computing approach to explore a hierarchical ranking network for a society of captive rhesus macaques. The computed network is sufficiently informative to address the question: Is the ranking network for a rhesus macaque society more like a kingdom or a corporation? Our computations are based on a three-step approach. These steps are devised to deal with the tremendous challenges stemming from the transitivity of dominance as a necessary constraint on the ranking relations among all individual macaques, and the very high sampling heterogeneity in the behavioral conflict data. The first step simultaneously infers the ranking potentials among all network members, which requires accommodation of heterogeneous measurement error inherent in behavioral data. Our second step estimates the social rank for all individuals by minimizing the network-wide errors in the ranking potentials. The third step provides a way to compute confidence bounds for selected empirical features in the social ranking. We apply this approach to two sets of conflict data pertaining to two captive societies of adult rhesus macaques. The resultant ranking network for each society is found to be a sophisticated mixture of both a kingdom and a corporation. Also, for validation purposes, we reanalyze conflict data from twenty longhorn sheep and demonstrate that our three-step approach is capable of correctly computing a ranking network by eliminating all ranking error.

  1. Delineating the Macroscale Areal Organization of the Macaque Cortex In Vivo

    Directory of Open Access Journals (Sweden)

    Ting Xu

    2018-04-01

    Full Text Available Summary: Complementing long-standing traditions centered on histology, fMRI approaches are rapidly maturing in delineating brain areal organization at the macroscale. The non-human primate (NHP provides the opportunity to overcome critical barriers in translational research. Here, we establish the data requirements for achieving reproducible and internally valid parcellations in individuals. We demonstrate that functional boundaries serve as a functional fingerprint of the individual animals and can be achieved under anesthesia or awake conditions (rest, naturalistic viewing, though differences between awake and anesthetized states precluded the detection of individual differences across states. Comparison of awake and anesthetized states suggested a more nuanced picture of changes in connectivity for higher-order association areas, as well as visual and motor cortex. These results establish feasibility and data requirements for the generation of reproducible individual-specific parcellations in NHPs, provide insights into the impact of scan state, and motivate efforts toward harmonizing protocols. : Noninvasive fMRI in macaques is an essential tool in translation research. Xu et al. establish the individual functional parcellation of the macaque cortex and demonstrate that brain organization is unique, reproducible, and valid, serving as a fingerprint for an individual macaque. Keywords: macaque, parcellation, cortical areas, gradient, functional connectivity

  2. Plasticity of Ability to Form Cross-Modal Representations in Infant Japanese Macaques

    Science.gov (United States)

    Adachi, Ikuma; Kuwahata, Hiroko; Fujita, Kazuo; Tomonaga, Masaki; Matsuzawa, Tetsuro

    2009-01-01

    In a previous study, Adachi, Kuwahata, Fujita, Tomonaga & Matsuzawa demonstrated that infant Japanese macaques (Macaca fuscata) form cross-modal representations of conspecifics but not of humans. However, because the subjects in the experiment were raised in a large social group and had considerably less exposure to humans than to…

  3. An SIV/macaque model targeted to study HIV-associated neurocognitive disorders.

    Science.gov (United States)

    Beck, Sarah E; Queen, Suzanne E; Metcalf Pate, Kelly A; Mangus, Lisa M; Abreu, Celina M; Gama, Lucio; Witwer, Kenneth W; Adams, Robert J; Zink, M Christine; Clements, Janice E; Mankowski, Joseph L

    2018-04-01

    Simian immunodeficiency virus (SIV) infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HIV-associated neurocognitive disorders (HAND) for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high-translational value. Similar to observations in HIV-infected patients receiving antiretroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART. By developing quantitative viral outgrowth assays that measure both CD4+ T cells and macrophages harboring replication competent SIV as well as a highly sensitive mouse-based viral outgrowth assay, we have positioned the SIV/pigtailed macaque model to advance our understanding of latent cellular reservoirs, including potential CNS reservoirs, to promote HIV cure. In addition to contributing to our understanding of the pathogenesis of HAND, the SIV/pigtailed macaque model also provides an excellent opportunity to test innovative approaches to eliminate the latent HIV reservoir in the brain.

  4. Ranking network of a captive rhesus macaque society: a sophisticated corporative kingdom.

    Directory of Open Access Journals (Sweden)

    Hsieh Fushing

    2011-03-01

    Full Text Available We develop a three-step computing approach to explore a hierarchical ranking network for a society of captive rhesus macaques. The computed network is sufficiently informative to address the question: Is the ranking network for a rhesus macaque society more like a kingdom or a corporation? Our computations are based on a three-step approach. These steps are devised to deal with the tremendous challenges stemming from the transitivity of dominance as a necessary constraint on the ranking relations among all individual macaques, and the very high sampling heterogeneity in the behavioral conflict data. The first step simultaneously infers the ranking potentials among all network members, which requires accommodation of heterogeneous measurement error inherent in behavioral data. Our second step estimates the social rank for all individuals by minimizing the network-wide errors in the ranking potentials. The third step provides a way to compute confidence bounds for selected empirical features in the social ranking. We apply this approach to two sets of conflict data pertaining to two captive societies of adult rhesus macaques. The resultant ranking network for each society is found to be a sophisticated mixture of both a kingdom and a corporation. Also, for validation purposes, we reanalyze conflict data from twenty longhorn sheep and demonstrate that our three-step approach is capable of correctly computing a ranking network by eliminating all ranking error.

  5. New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca fasicularis).

    Science.gov (United States)

    Matthews, Kristin A; Tonsho, Makoto; Madsen, Joren C

    2015-08-01

    A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with inappetence and weight loss 57 d after heterotopic heart and thymus transplantation while receiving an immunosuppressant regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis performed at presentation revealed elevated blood glucose and glycated hemoglobin (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria. Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately. The macaque was weaned off the immunosuppressive therapy as his clinical condition improved and stabilized. Approximately 74 d after discontinuation of the immunosuppressants, the blood glucose normalized, and the insulin therapy was stopped. The animal's blood glucose and HbA1c values have remained within normal limits since this time. We suspect that our macaque experienced new-onset diabetes mellitus after transplantation, a condition that is commonly observed in human transplant patients but not well described in NHP. To our knowledge, this report represents the first documented case of new-onset diabetes mellitus after transplantation in a cynomolgus macaque.

  6. Survey of Treponemal Infections in Free-Ranging and Captive Macaques, 1999–2012

    Science.gov (United States)

    Klegarth, Amy R.; Ezeonwu, Chigozie A.; Rompis, Aida; Lee, Benjamin P.Y.-H.; Aggimarangsee, Nantiya; Chalise, Mukesh; Cortes, John; Feeroz, M.; Molini, Barbara J.; Godornes, Bess C.; Marks, Michael; Schillaci, Michael; Engel, Gregory; Knauf, Sascha; Lukehart, Sheila A.

    2017-01-01

    Survey results showed treponemal infection among pet macaques in Southeast Asia, a region with a high prevalence of human yaws. This finding, along with studies showing treponemal infection in nonhuman primates in Africa, should encourage a One Health approach to yaws eradication and surveillance activities, possibly including monitoring of nonhuman primates in yaws-endemic regions. PMID:28418297

  7. Diet of the Assamese macaque Macaca assamensis in lime-stone habitats of Nonggang, China

    Directory of Open Access Journals (Sweden)

    Qihai ZHOU, Hua WEI, Zhonghao HUANG, Chengming HUANG

    2011-02-01

    Full Text Available To enhance our understanding of dietary adaptations in macaques we studied the diet of the Assamese macaque Macaca assamensis in limestone seasonal rain forests at Nonggang Nature Reserve, China from September 2005 to August 2006. Our results show that although macaques fed on many plant species, 85.2% of the diet came from only 12 species, of which a bamboo species, Indocalamus calcicolus contributed to 62% of the diet. Young leaves were staple food items (74.1% of the diet for Assamese macaques at Nonggang, and constituted the bulk of monthly diets almost year-round, ranging from 44.9% (July to 92.9% (May. Young parts of Indocalamus calcicolus unexpanded leaves contributed to a large proportion of the young leaf diet in most months. Fruit accounted for only 17.4% of the diet, with a peak of consumption in July. We suggest that this highly folivorous diet may be related to the long lean season of fruit availability in limestone habitats as well as the utilization of cliffs of low fruit availability [Current Zoology 57 (1: 18–25, 2011].

  8. Young macaques (Macaca fascicularis) preferentially bias attention towards closer, older, and better tool users.

    Science.gov (United States)

    Tan, Amanda W Y; Hemelrijk, Charlotte K; Malaivijitnond, Suchinda; Gumert, Michael D

    2018-05-12

    Examining how animals direct social learning during skill acquisition under natural conditions, generates data for examining hypotheses regarding how transmission biases influence cultural change in animal populations. We studied a population of macaques on Koram Island, Thailand, and examined model-based biases during interactions by unskilled individuals with tool-using group members. We first compared the prevalence of interactions (watching, obtaining food, object exploration) and proximity to tool users during interactions, in developing individuals (infants, juveniles) versus mature non-learners (adolescents, adults), to provide evidence that developing individuals are actively seeking information about tool use from social partners. All infants and juveniles, but only 49% of mature individuals carried out interacted with tool users. Macaques predominantly obtained food by scrounging or stealing, suggesting maximizing scrounging opportunities motivates interactions with tool users. However, while interactions by adults was limited to obtaining food, young macaques and particularly infants also watched tool users and explored objects, indicating additional interest in tool use itself. We then ran matrix correlations to identify interaction biases, and what attributes of tool users influenced these. Biases correlated with social affiliation, but macaques also preferentially targeted tool users that potentially increase scrounging and learning opportunities. Results suggest that social structure may constrain social learning, but the motivation to bias interactions towards tool users to maximize feeding opportunities may also socially modulate learning by facilitating close proximity to better tool users, and further interest in tool-use actions and materials, especially during development.

  9. Ethical and legal challenges of vaccines and vaccination: Reflections.

    Science.gov (United States)

    Jesani, Amar; Johari, Veena

    2017-01-01

    Vaccines and vaccination have emerged as key medical scientific tools for prevention of certain diseases. Documentation of the history of vaccination shows that the initial popular resistance to universal vaccination was based on false assumptions and eventually gave way to acceptance of vaccines and trust in their ability to save lives. The successes of the global eradication of smallpox, and now of polio, have only strengthened the premier position occupied by vaccines in disease prevention. However, the success of vaccines and public trust in their ability to eradicate disease are now under challenge, as increasing numbers of people refuse vaccination, questioning the effectiveness of vaccines and the need to vaccinate.

  10. Laser facilitates vaccination

    Directory of Open Access Journals (Sweden)

    Ji Wang

    2016-01-01

    Full Text Available Development of novel vaccine deliveries and vaccine adjuvants is of great importance to address the dilemma that the vaccine field faces: to improve vaccine efficacy without compromising safety. Harnessing the specific effects of laser on biological systems, a number of novel concepts have been proposed and proved in recent years to facilitate vaccination in a safer and more efficient way. The key advantage of using laser technology in vaccine delivery and adjuvantation is that all processes are initiated by physical effects with no foreign chemicals administered into the body. Here, we review the recent advances in using laser technology to facilitate vaccine delivery and augment vaccine efficacy as well as the underlying mechanisms.

  11. Vaccine Safety Datalink

    Science.gov (United States)

    The Vaccine Safety Datalink is part of the National Immunization Program within the Centers for Disease Control and Prevention and was started in recognition of gaps in the scientific knowledge of rare vaccine side effects.

  12. The HPV Vaccination Crisis

    Science.gov (United States)

    Following the release of a consensus statement from the NCI-Designated Cancer Centers urging HPV vaccination in the United States, Dr. Noel Brewer discusses the country’s low vaccination rates and how clinicians can help to improve them.

  13. Your child's first vaccines

    Science.gov (United States)

    ... term seizures, coma, lowered consciousness, and permanent brain damage have been reported following DTaP vaccination. These reports are extremely rare. Pneumococcal Vaccine Mild Problems: drowsiness or temporary loss of appetite ( ...

  14. Your Baby's First Vaccines

    Science.gov (United States)

    ... term seizures, coma, lowered consciousness, and permanent brain damage have been reported following DTaP vaccination. These reports are extremely rare. Pneumococcal Vaccine Mild Problems: Drowsiness or temporary loss of appetite ( ...

  15. Vaccines in Multiple Sclerosis.

    Science.gov (United States)

    Williamson, Eric M L; Chahin, Salim; Berger, Joseph R

    2016-04-01

    Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.

  16. Vaccines and immunization

    African Journals Online (AJOL)

    Prof Ezechukwu

    vaccines for malaria and HIV infection. Despite the ... decades, effective vaccines against the major causes of ... challenge antibodies, specific helper and effector T lymphocytes ... materials to produced immunity to a disease. It was originally ...

  17. Pneumococcal Vaccines (PCV, PPSV)

    Science.gov (United States)

    ... Educators Search English Español Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth / For Parents / Your Child's Immunizations: ... cochlear implants. Why Are the PCV and PPSV Vaccines Recommended? Children younger than 2 years old, adults ...

  18. Directed shift of vaginal microbiota induced by vaginal application of sucrose gel in rhesus macaques.

    Science.gov (United States)

    Hu, Kai-tao; Zheng, Jin-xin; Yu, Zhi-jian; Chen, Zhong; Cheng, Hang; Pan, Wei-guang; Yang, Wei-zhi; Wang, Hong-yan; Deng, Qi-wen; Zeng, Zhong-ming

    2015-04-01

    Sucrose gel was used to treat bacterial vaginosis in a phase III clinical trial. However, the changes of vaginal flora after treatment were only examined by Nugent score in that clinical trial, While the vaginal microbiota of rhesus macaques is characterized by anaerobic, Gram-negative bacteria, few lactobacilli, and pH levels above 4.6, similar to the microbiota of patients with bacterial vaginosis. This study is aimed to investigate the change of the vaginal microbiota of rehsus macaques after topical use of sucrose gel to reveal more precisely the bacterial population shift after the topical application of sucrose gel. Sixteen rhesus macaques were treated with 0.5 g sucrose gel vaginally and three with 0.5 g of placebo gel. Vaginal swabs were collected daily following treatment. Vaginal pH levels and Nugent scores were recorded. The composition of the vaginal micotbiota was tested by V3∼V4 16S rDNA metagenomic sequencing. Dynamic changes in the Lactobacillus genus were analyzed by qPCR. The vaginal microbiota of rhesus macaques are dominated by anaerobic Gram-negative bacteria, with few lactobacilli and high pH levels above 4.6. After five days' treatment with topical sucrose gel, the component percentage of Lactobacillus in vaginal microbiota increased from 1.31% to 81.59%, while the component percentage of Porphyromonas decreased from 18.60% to 0.43%, Sneathia decreased from 15.09% to 0.89%, Mobiluncus decreased from 8.23% to 0.12%, etc.. The average vaginal pH values of 16 rhesus macaques of the sucrose gel group decreased from 5.4 to 3.89. There were no significant changes in microbiota and vaginal pH observed in the placebo group. Rhesus macaques can be used as animal models of bacterial vaginosis to develop drugs and test treatment efficacy. Furthermore, the topical application of sucrose gel induced the shifting of vaginal flora of rhesus macaques from a BV kind of flora to a lactobacilli-dominating flora. Copyright © 2015 The Authors. Published by

  19. Latent Membrane Protein 1 as a molecular adjuvant for single-cycle lentiviral vaccines

    Directory of Open Access Journals (Sweden)

    Rahmberg Andrew R

    2011-05-01

    Full Text Available Abstract Background Molecular adjuvants are a promising method to enhance virus-specific immune responses and protect against HIV-1 infection. Immune activation by ligands for receptors such as CD40 can induce dendritic cell activation and maturation. Here we explore the incorporation of two CD40 mimics, Epstein Barr Virus gene LMP1 or an LMP1-CD40 chimera, into a strain of SIV that was engineered to be limited to a single cycle of infection. Results Full length LMP1 or the chimeric protein LMP1-CD40 was cloned into the nef-locus of single-cycle SIV. Human and Macaque monocyte derived macrophages and DC were infected with these viruses. Infected cells were analyzed for activation surface markers by flow cytometry. Cells were also analyzed for secretion of pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-12p70 and TNF by cytometric bead array. Conclusions Overall, single-cycle SIV expressing LMP1 and LMP1-CD40 produced a broad and potent TH1-biased immune response in human as well as rhesus macaque macrophages and DC when compared with control virus. Single-cycle SIV-LMP1 also enhanced antigen presentation by lentiviral vector vaccines, suggesting that LMP1-mediated immune activation may enhance lentiviral vector vaccines against HIV-1.

  20. [Mumps vaccine virus transmission].

    Science.gov (United States)

    Otrashevskaia, E V; Kulak, M V; Otrashevskaia, A V; Karpov, I A; Fisenko, E G; Ignat'ev, G M

    2013-01-01

    In this work we report the mumps vaccine virus shedding based on the laboratory confirmed cases of the mumps virus (MuV) infection. The likely epidemiological sources of the transmitted mumps virus were children who were recently vaccinated with the mumps vaccine containing Leningrad-Zagreb or Leningrad-3 MuV. The etiology of the described cases of the horizontal transmission of both mumps vaccine viruses was confirmed by PCR with the sequential restriction analysis.

  1. Rotavirus vaccines: an overview.

    OpenAIRE

    Midthun, K; Kapikian, A Z

    1996-01-01

    Rotavirus vaccine development has focused on the delivery of live attenuated rotavirus strains by the oral route. The initial "Jennerian" approach involving bovine (RIT4237, WC3) or rhesus (RRV) rotavirus vaccine candidates showed that these vaccines were safe, well tolerated, and immunogenic but induced highly variable rates of protection against rotavirus diarrhea. The goal of a rotavirus vaccine is to prevent severe illness that can lead to dehydration in infants and young children in both...

  2. Adaptive evolution of simian immunodeficiency viruses isolated from two conventional progressor macaques with neuroaids

    Energy Technology Data Exchange (ETDEWEB)

    Foley, Brian T [Los Alamos National Laboratory; Korber, Bette T [Los Alamos National Laboratory

    2008-01-01

    Simian immunodeficiency virus infection of macaques may result in neuroAIDS, a feature more commonly observed in macaques with rapid progressive disease than in those with conventional disease. This is the first report of two conventional progressors (H631 and H636) with encephalitis in rhesus macaques inoculated with a derivative of SIVsmES43-3. Phylogenetic analyses of viruses isolated from the cerebral spinal fluid (CSF) and plasma from both animals demonstrated tissue compartmentalization. Additionally, virus from the central nervous system (CNS) was able to infect primary macaque monocyte-derived macrophages more efficiently than virus from plasma. Conversely, virus isolated from plasma was able to replicate better in peripheral blood mononuclear cells than virus from CNS. We speculate that these viruses were under different selective pressures in their separate compartments. Furthermore, these viruses appear to have undergone adaptive evolution to preferentially replicate in their respective cell targets. Analysis of the number of potential N-linked glycosylation sites (PNGS) in gp160 showed that there was a statistically significant loss of PNGS in viruses isolated from CNS in both macaques compared to SIVsmE543-3. Moreover, virus isolated from the brain in H631, had statistically significant loss of PNGS compared to virus isolated from CSF and plasma of the same animal. It is possible that the brain isolate may have adapted to decrease the number of PNGS given that humoral immune selection pressure is less likely to be encountered in the brain. These viruses provide a relevant model to study the adaptations required for SIV to induce encephalitis.

  3. Beneficial effect of hot spring bathing on stress levels in Japanese macaques.

    Science.gov (United States)

    Takeshita, Rafaela S C; Bercovitch, Fred B; Kinoshita, Kodzue; Huffman, Michael A

    2018-05-01

    The ability of animals to survive dramatic climates depends on their physiology, morphology and behaviour, but is often influenced by the configuration of their habitat. Along with autonomic responses, thermoregulatory behaviours, including postural adjustments, social aggregation, and use of trees for shelter, help individuals maintain homeostasis across climate variations. Japanese macaques (Macaca fuscata) are the world's most northerly species of nonhuman primates and have adapted to extremely cold environments. Given that thermoregulatory stress can increase glucocorticoid concentrations in primates, we hypothesized that by using an available hot spring, Japanese macaques could gain protection against weather-induced cold stress during winter. We studied 12 adult female Japanese macaques living in Jigokudani Monkey Park, Japan, during the spring birth season (April to June) and winter mating season (October to December). We collected faecal samples for determination of faecal glucocorticoid (fGC) metabolite concentrations by enzyme immunoassay, as well as behavioural data to determine time spent in the hot springs, dominance rank, aggression rates, and affiliative behaviours. We used nonparametric statistics to examine seasonal changes in hot spring bathing, and the relationship between rank and air temperature on hot spring bathing. We used general linear mixed-effect models to examine factors impacting hormone concentrations. We found that Japanese macaques use hot spring bathing for thermoregulation during the winter. In the studied troop, the single hot spring is a restricted resource favoured by dominant females. High social rank had both costs and benefits: dominant females sustained high fGC levels, which were associated with high aggression rates in winter, but benefited by priority of access to the hot spring, which was associated with low fGC concentrations and therefore might help reduce energy expenditure and subsequent body heat loss. This unique

  4. A MIV-150/zinc acetate gel inhibits SHIV-RT infection in macaque vaginal explants.

    Science.gov (United States)

    Barnable, Patrick; Calenda, Giulia; Ouattara, Louise; Gettie, Agegnehu; Blanchard, James; Jean-Pierre, Ninochka; Kizima, Larisa; Rodríguez, Aixa; Abraham, Ciby; Menon, Radhika; Seidor, Samantha; Cooney, Michael L; Roberts, Kevin D; Sperling, Rhoda; Piatak, Michael; Lifson, Jeffrey D; Fernandez-Romero, Jose A; Zydowsky, Thomas M; Robbiani, Melissa; Teleshova, Natalia

    2014-01-01

    To extend our observations that single or repeated application of a gel containing the NNRTI MIV-150 (M) and zinc acetate dihydrate (ZA) in carrageenan (CG) (MZC) inhibits vaginal transmission of simian/human immunodeficiency virus (SHIV)-RT in macaques, we evaluated safety and anti-SHIV-RT activity of MZC and related gel formulations ex vivo in macaque mucosal explants. In addition, safety was further evaluated in human ectocervical explants. The gels did not induce mucosal toxicity. A single ex vivo exposure to diluted MZC (1∶30, 1∶100) and MC (1∶30, the only dilution tested), but not to ZC gel, up to 4 days prior to viral challenge, significantly inhibited SHIV-RT infection in macaque vaginal mucosa. MZC's activity was not affected by seminal plasma. The antiviral activity of unformulated MIV-150 was not enhanced in the presence of ZA, suggesting that the antiviral activity of MZC was mediated predominantly by MIV-150. In vivo administration of MZC and CG significantly inhibited ex vivo SHIV-RT infection (51-62% inhibition relative to baselines) of vaginal (but not cervical) mucosa collected 24 h post last gel exposure, indicating barrier effect of CG. Although the inhibitory effect of MZC (65-74%) did not significantly differ from CG (32-45%), it was within the range of protection (∼75%) against vaginal SHIV-RT challenge 24 h after gel dosing. Overall, the data suggest that evaluation of candidate microbicides in macaque explants can inform macaque efficacy and clinical studies design. The data support advancing MZC gel for clinical evaluation.

  5. Noninvasive scalp recording of cortical auditory evoked potentials in the alert macaque monkey.

    Science.gov (United States)

    Itoh, Kosuke; Nejime, Masafumi; Konoike, Naho; Nakada, Tsutomu; Nakamura, Katsuki

    2015-09-01

    Scalp-recorded evoked potentials (EP) provide researchers and clinicians with irreplaceable means for recording stimulus-related neural activities in the human brain, due to its high temporal resolution, handiness, and, perhaps more importantly, non-invasiveness. This work recorded the scalp cortical auditory EP (CAEP) in unanesthetized monkeys by using methods that are essentially identical to those applied to humans. Young adult rhesus monkeys (Macaca mulatta, 5-7 years old) were seated in a monkey chair, and their head movements were partially restricted by polystyrene blocks and tension poles placed around their head. Individual electrodes were fixated on their scalp using collodion according to the 10-20 system. Pure tone stimuli were presented while electroencephalograms were recorded from up to nineteen channels, including an electrooculogram channel. In all monkeys (n = 3), the recorded CAEP comprised a series of positive and negative deflections, labeled here as macaque P1 (mP1), macaque N1 (mN1), macaque P2 (mP2), and macaque N2 (mN2), and these transient responses to sound onset were followed by a sustained potential that continued for the duration of the sound, labeled the macaque sustained potential (mSP). mP1, mN2 and mSP were the prominent responses, and they had maximal amplitudes over frontal/central midline electrode sites, consistent with generators in auditory cortices. The study represents the first noninvasive scalp recording of CAEP in alert rhesus monkeys, to our knowledge. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251.

    Science.gov (United States)

    Andrews, Chasity D; Bernard, Leslie St; Poon, Amanda Yee; Mohri, Hiroshi; Gettie, Natanya; Spreen, William R; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Hong, Zhi; Ho, David D; Markowitz, Martin

    2017-02-20

    We evaluated the effectiveness of cabotegravir (CAB; GSK1265744 or GSK744) long acting as preexposure prophylaxis (PrEP) against intravenous simian immunodeficiency virus (SIV) challenge in a model that mimics blood transfusions based on the per-act probability of infection. CAB long acting is an integrase strand transfer inhibitor formulated as a 200 mg/ml injectable nanoparticle suspension that is an effective PrEP agent against rectal and vaginal simian/human immunodeficiency virus transmission in macaques. Three groups of rhesus macaques (n = 8 per group) were injected intramuscularly with CAB long acting and challenged intravenously with 17 animal infectious dose 50% SIVmac251 on week 2. Group 1 was injected with 50 mg/kg on week 0 and 4 to evaluate the protective efficacy of the CAB long-acting dose used in macaque studies mimicking sexual transmission. Group 2 was injected with 50 mg/kg on week 0 to evaluate the necessity of the second injection of CAB long acting for protection against intravenous challenge. Group 3 was injected with 25 mg/kg on week 0 and 50 mg/kg on week 4 to correlate CAB plasma concentrations at the time of challenge with protection. Five additional macaques remained untreated as controls. CAB long acting was highly protective with 21 of the 24 CAB long-acting-treated macaques remaining aviremic, resulting in 88% protection. The plasma CAB concentration at the time of virus challenge appeared to be more important for protection than sustaining therapeutic plasma concentrations with the second CAB long acting injection. These results support the clinical investigation of CAB long acting as PrEP in people who inject drugs.

  7. A MIV-150/zinc acetate gel inhibits SHIV-RT infection in macaque vaginal explants.

    Directory of Open Access Journals (Sweden)

    Patrick Barnable

    Full Text Available To extend our observations that single or repeated application of a gel containing the NNRTI MIV-150 (M and zinc acetate dihydrate (ZA in carrageenan (CG (MZC inhibits vaginal transmission of simian/human immunodeficiency virus (SHIV-RT in macaques, we evaluated safety and anti-SHIV-RT activity of MZC and related gel formulations ex vivo in macaque mucosal explants. In addition, safety was further evaluated in human ectocervical explants. The gels did not induce mucosal toxicity. A single ex vivo exposure to diluted MZC (1∶30, 1∶100 and MC (1∶30, the only dilution tested, but not to ZC gel, up to 4 days prior to viral challenge, significantly inhibited SHIV-RT infection in macaque vaginal mucosa. MZC's activity was not affected by seminal plasma. The antiviral activity of unformulated MIV-150 was not enhanced in the presence of ZA, suggesting that the antiviral activity of MZC was mediated predominantly by MIV-150. In vivo administration of MZC and CG significantly inhibited ex vivo SHIV-RT infection (51-62% inhibition relative to baselines of vaginal (but not cervical mucosa collected 24 h post last gel exposure, indicating barrier effect of CG. Although the inhibitory effect of MZC (65-74% did not significantly differ from CG (32-45%, it was within the range of protection (∼75% against vaginal SHIV-RT challenge 24 h after gel dosing. Overall, the data suggest that evaluation of candidate microbicides in macaque explants can inform macaque efficacy and clinical studies design. The data support advancing MZC gel for clinical evaluation.

  8. Vaccination: problems and perspectives.

    Directory of Open Access Journals (Sweden)

    S. M. Kharit

    2009-01-01

    Full Text Available Massive vaccination had proved its effective morbidity reduction. Today it is necessary to extend vaccination schedule, creation of selective, regional schedules based on epidemiological, clinical, economical substantiation. Development of vaccination needs the profound scientific research, modernization of adverse reaction observing system, betterment training system and awareness of population.

  9. Oral vaccination of fish

    NARCIS (Netherlands)

    Embregts, Carmen W.E.; Forlenza, Maria

    2016-01-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen

  10. Meningococcal Vaccine (For Parents)

    Science.gov (United States)

    ... previous dose of meningococcal vaccine, to the DTaP vaccine , or to latex If your child has a history of Guillain-Barré syndrome (a disease of the nervous system that causes progressive weakness), talk to your doctor about whether the vaccines are a good idea. Caring for Your Child ...

  11. Hepatitis A Vaccine

    Science.gov (United States)

    Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... Why get vaccinated against hepatitis A?Hepatitis A is a serious liver disease. It is caused by the hepatitis A virus (HAV). HAV is spread from ...

  12. Asymmetric Dichoptic Masking in Visual Cortex of Amblyopic Macaque Monkeys.

    Science.gov (United States)

    Shooner, Christopher; Hallum, Luke E; Kumbhani, Romesh D; García-Marín, Virginia; Kelly, Jenna G; Majaj, Najib J; Movshon, J Anthony; Kiorpes, Lynne

    2017-09-06

    In amblyopia, abnormal visual experience leads to an extreme form of eye dominance, in which vision through the nondominant eye is degraded. A key aspect of this disorder is perceptual suppression: the image seen by the stronger eye often dominates during binocular viewing, blocking the image of the weaker eye from reaching awareness. Interocular suppression is the focus of ongoing work aimed at understanding and treating amblyopia, yet its physiological basis remains unknown. We measured binocular interactions in visual cortex of anesthetized amblyopic monkeys (female Macaca nemestrina ), using 96-channel "Utah" arrays to record from populations of neurons in V1 and V2. In an experiment reported recently (Hallum et al., 2017), we found that reduced excitatory input from the amblyopic eye (AE) revealed a form of balanced binocular suppression that is unaltered in amblyopia. Here, we report on the modulation of the gain of excitatory signals from the AE by signals from its dominant fellow eye (FE). Using a dichoptic masking technique, we found that AE responses to grating stimuli were attenuated by the presentation of a noise mask to the FE, as in a normal control animal. Responses to FE stimuli, by contrast, could not be masked from the AE. We conclude that a weakened ability of the amblyopic eye to modulate cortical response gain creates an imbalance of suppression that favors the dominant eye. SIGNIFICANCE STATEMENT In amblyopia, vision in one eye is impaired as a result of abnormal early visual experience. Behavioral observations in humans with amblyopia suggest that much of their visual loss is due to active suppression of their amblyopic eye. Here we describe experiments in which we studied binocular interactions in macaques with experimentally induced amblyopia. In normal monkeys, the gain of neuronal response to stimulation of one eye is modulated by contrast in the other eye, but in monkeys with amblyopia the balance of gain modulation is altered so that

  13. Sustainable vaccine development: a vaccine manufacturer's perspective.

    Science.gov (United States)

    Rappuoli, Rino; Hanon, Emmanuel

    2018-05-08

    Vaccination remains the most cost-effective public health intervention after clean water, and the benefits impressively outweigh the costs. The efforts needed to fulfill the steadily growing demands for next-generation and novel vaccines designed for emerging pathogens and new indications are only realizable in a sustainable business model. Vaccine development can be fast-tracked through strengthening international collaborations, and the continuous innovation of technologies to accelerate their design, development, and manufacturing. However, these processes should be supported by a balanced project portfolio, and by managing sustainable vaccine procurement strategies for different types of markets. Collectively this will allow a gradual shift to a more streamlined and profitable vaccine production, which can significantly contribute to the worldwide effort to shape global health. Copyright © 2018 GlaxoSmithKine Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

  14. Study of the safety, immunogenicity and efficacy of attenuated and killed Leishmania (Leishmania major vaccines in a rhesus monkey (Macaca mulatta model of the human disease

    Directory of Open Access Journals (Sweden)

    VF Amaral

    2002-10-01

    Full Text Available We have compared the efficacy of two Leishmania (Leishmania major vaccines, one genetically attenuated (DHFR-TS deficient organisms, the other inactivated [autoclaved promastigotes (ALM with bacillus Calmete-Guérin (BCG], in protecting rhesus macaques (Macaca mulatta against infection with virulent L. (L. major. Positive antigen-specific recall proliferative response was observed in vaccinees (79% in attenuated parasite-vaccinated monkeys, versus 75% in ALM-plus-BCG-vaccinated animals, although none of these animals exhibited either augmented in vitro gamma interferon (IFN-g production or positive delayed-type hypersensitivity (DTH response to the leishmanin skin test prior to the challenge. Following challenge, there were significant differences in blastogenic responses (p < 0.05 between attenuated-vaccinated monkeys and naïve controls. In both vaccinated groups very low levels of antibody were found before challenge, which increased after infective challenge. Protective immunity did not follow vaccination, in that monkeys exhibited skin lesion at the site of challenge in all the groups. The most striking result was the lack of pathogenicity of the attenuated parasite, which persisted in infected animals for up to three months, but were incapable of causing disease under the conditions employed. We concluded that both vaccine protocols used in this study are safe in primates, but require further improvement for vaccine application.

  15. Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment, Learning, and Social Behavior

    Science.gov (United States)

    Curtis, Britni; Liberato, Noelle; Rulien, Megan; Morrisroe, Kelly; Kenney, Caroline; Yutuc, Vernon; Ferrier, Clayton; Marti, C. Nathan; Mandell, Dorothy; Burbacher, Thomas M.; Sackett, Gene P.

    2015-01-01

    Background In the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in light of the much expanded and more complex schedule in place today. Objectives The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model. Methods We administered vaccines to six groups of infant male rhesus macaques (n = 12–16/group) using a standardized thimerosal dose where appropriate. Study groups included the recommended 1990s Pediatric vaccine schedule, an accelerated 1990s Primate schedule with or without the measles–mumps–rubella (MMR) vaccine, the MMR vaccine only, and the expanded 2008 schedule. We administered saline injections to age-matched control animals (n = 16). Infant development was assessed from birth to 12 months of age by examining the acquisition of neonatal reflexes, the development of object concept permanence (OCP), computerized tests of discrimination learning, and infant social behavior. Data were analyzed using analysis of variance, multilevel modeling, and survival analyses, where appropriate. Results We observed no group differences in the acquisition of OCP. During discrimination learning, animals receiving TCVs had improved performance on reversal testing, although some of these same animals showed poorer performance in subsequent learning-set testing. Analysis of social and nonsocial behaviors identified few instances of negative behaviors across the entire infancy period. Although some group differences in specific behaviors were reported at 2 months of age, by 12 months all infants, irrespective of vaccination status, had developed the typical repertoire of macaque behaviors. Conclusions This comprehensive 5-year case–control study, which closely examined

  16. Peptide Vaccines for Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Rory C. F. De Brito

    2018-05-01

    Full Text Available Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

  17. Peptide Vaccines for Leishmaniasis.

    Science.gov (United States)

    De Brito, Rory C F; Cardoso, Jamille M De O; Reis, Levi E S; Vieira, Joao F; Mathias, Fernando A S; Roatt, Bruno M; Aguiar-Soares, Rodrigo Dian D O; Ruiz, Jeronimo C; Resende, Daniela de M; Reis, Alexandre B

    2018-01-01

    Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

  18. Vaccines as Epidemic Insurance.

    Science.gov (United States)

    Pauly, Mark V

    2017-10-27

    This paper explores the relationship between the research for and development of vaccines against global pandemics and insurance. It shows that development in advance of pandemics of a portfolio of effective and government-approved vaccines does have some insurance properties: it requires incurring costs that are certain (the costs of discovering, developing, and testing vaccines) in return for protection against large losses (if a pandemic treatable with one of the vaccines occurs) but also with the possibility of no benefit (from a vaccine against a disease that never reaches the pandemic stage). It then argues that insurance against the latter event might usefully be offered to organizations developing vaccines, and explores the benefits of insurance payments to or on behalf of countries who suffer from unpredictable pandemics. These ideas are then related to recent government, industry, and philanthropic efforts to develop better policies to make vaccines against pandemics available on a timely basis.

  19. Vaccines as Epidemic Insurance

    Directory of Open Access Journals (Sweden)

    Mark V. Pauly

    2017-10-01

    Full Text Available This paper explores the relationship between the research for and development of vaccines against global pandemics and insurance. It shows that development in advance of pandemics of a portfolio of effective and government-approved vaccines does have some insurance properties: it requires incurring costs that are certain (the costs of discovering, developing, and testing vaccines in return for protection against large losses (if a pandemic treatable with one of the vaccines occurs but also with the possibility of no benefit (from a vaccine against a disease that never reaches the pandemic stage. It then argues that insurance against the latter event might usefully be offered to organizations developing vaccines, and explores the benefits of insurance payments to or on behalf of countries who suffer from unpredictable pandemics. These ideas are then related to recent government, industry, and philanthropic efforts to develop better policies to make vaccines against pandemics available on a timely basis.

  20. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57 Section 410.57 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its...

  1. vaccination with newcastle disease vaccines strain i2 and lasota

    African Journals Online (AJOL)

    UP Employee

    mash feed as vaccine carriers was conducted. Newcastle disease vaccine strain I2 and. NDV La Sota vaccines provided protection to commercial and local chickens vaccinated through i/o, i/m or dw. No significant difference (P≤0.05) was observed in the antibody titre of commercial or local chickens vaccinated with either ...

  2. Pair housing for female longtailed and rhesus macaques in the laboratory: behavior in protected contact versus full contact.

    Science.gov (United States)

    Baker, Kate C; Crockett, Carolyn M; Lee, Grace H; Oettinger, Brooke C; Schoof, Valérie; Thom, Jinhee P

    2012-01-01

    Pair housing for caged macaques in the laboratory generally allows unrestricted tactile contact but, less commonly, may involve limited contact via grooming-contact bars or perforated panels. The purpose of using this protected contact housing, which prevents entry into pair-mates' cages, typically is to accommodate research and management requirements. The study used behavioral data collected on 12 pairs of female longtailed macaques (Macaca fascicularis) at the Washington National Primate Research Center and 7 pairs of female rhesus macaques (Macaca mulatta) housed at the Tulane National Primate Research Center to assess the relative benefits of protected versus full protected contact. The study collected data in stable pairs housed first in protected contact followed by full contact. Species combined, the study found the presence of the panel was associated with lower levels of social grooming and higher levels of self-grooming, abnormal behavior, and tension-related behavior. Within species, only the protected- versus full-contact contrasts for abnormal and tension were statistically significant-and only for rhesus macaques. Results suggest that for female rhesus macaques, potential disadvantages or inconveniences of full contact should be balanced against the improved behavioral profile in comparison to protected contact. The use of protected contact among female longtailed macaques does not appear to require the same cost-benefit analysis. Copyright © Taylor & Francis Group, LLC

  3. Enhancement of Mucosal Immunogenicity of Viral Vectored Vaccines by the NKT Cell Agonist Alpha-Galactosylceramide as Adjuvant

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    2014-10-01

    Full Text Available Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer, a synthetic glycolipid agonist of natural killer T (NKT cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors.

  4. Strong interferon-gamma mediated cellular immunity to scrub typhus demonstrated using a novel whole cell antigen ELISpot assay in rhesus macaques and humans.

    Directory of Open Access Journals (Sweden)

    Manutsanun Sumonwiriya

    2017-09-01

    Full Text Available Scrub typhus is a febrile infection caused by the obligate intracellular bacterium Orientia tsutsugamushi, which causes significant morbidity and mortality across the Asia-Pacific region. The control of this vector-borne disease is challenging due to humans being dead-end hosts, vertical maintenance of the pathogen in the vector itself, and a potentially large rodent reservoir of unclear significance, coupled with a lack of accurate diagnostic tests. Development of an effective vaccine is highly desirable. This however requires better characterization of the natural immune response of this neglected but important disease. Here we implement a novel IFN-γ ELISpot assay as a tool for studying O. tsutsugamushi induced cellular immune responses in an experimental scrub typhus rhesus macaque model and human populations. Whole cell antigen for O. tsutsugamushi (OT-WCA was prepared by heat inactivation of Karp-strain bacteria. Rhesus macaques were infected intradermally with O. tsutsugamushi. Freshly isolated peripheral blood mononuclear cells (PBMC from infected (n = 10 and uninfected animals (n = 5 were stimulated with OT-WCA, and IFN-γ secreting cells quantitated by ELISpot assay at five time points over 28 days. PBMC were then assayed from people in a scrub typhus-endemic region of Thailand (n = 105 and responses compared to those from a partially exposed population in a non-endemic region (n = 14, and to a naïve population in UK (n = 12. Mean results at Day 0 prior to O. tsutsugamushi infection were 12 (95% CI 0-25 and 15 (2-27 spot-forming cells (SFC/106 PBMC for infected and control macaques respectively. Strong O. tsutsugamushi-specific IFN-γ responses were seen post infection, with ELISpot responses 20-fold higher than baseline at Day 7 (mean 235, 95% CI 200-270 SFC/106 PBMC, 105-fold higher at Day 14 (mean 1261, 95% CI 1,097-1,425 SFC/106 PBMC, 125-fold higher at Day 21 (mean 1,498, 95% CI 1,496-1,500 SFC/106 PBMC and 118-fold higher at

  5. Strong interferon-gamma mediated cellular immunity to scrub typhus demonstrated using a novel whole cell antigen ELISpot assay in rhesus macaques and humans.

    Science.gov (United States)

    Sumonwiriya, Manutsanun; Paris, Daniel H; Sunyakumthorn, Piyanate; Anantatat, Tippawan; Jenjaroen, Kemajittra; Chumseng, Suchintana; Im-Erbsin, Rawiwan; Tanganuchitcharnchai, Ampai; Jintaworn, Suthatip; Blacksell, Stuart D; Chowdhury, Fazle R; Kronsteiner, Barbara; Teparrukkul, Prapit; Burke, Robin L; Lombardini, Eric D; Richards, Allen L; Mason, Carl J; Jones, James W; Day, Nicholas P J; Dunachie, Susanna J

    2017-09-01

    Scrub typhus is a febrile infection caused by the obligate intracellular bacterium Orientia tsutsugamushi, which causes significant morbidity and mortality across the Asia-Pacific region. The control of this vector-borne disease is challenging due to humans being dead-end hosts, vertical maintenance of the pathogen in the vector itself, and a potentially large rodent reservoir of unclear significance, coupled with a lack of accurate diagnostic tests. Development of an effective vaccine is highly desirable. This however requires better characterization of the natural immune response of this neglected but important disease. Here we implement a novel IFN-γ ELISpot assay as a tool for studying O. tsutsugamushi induced cellular immune responses in an experimental scrub typhus rhesus macaque model and human populations. Whole cell antigen for O. tsutsugamushi (OT-WCA) was prepared by heat inactivation of Karp-strain bacteria. Rhesus macaques were infected intradermally with O. tsutsugamushi. Freshly isolated peripheral blood mononuclear cells (PBMC) from infected (n = 10) and uninfected animals (n = 5) were stimulated with OT-WCA, and IFN-γ secreting cells quantitated by ELISpot assay at five time points over 28 days. PBMC were then assayed from people in a scrub typhus-endemic region of Thailand (n = 105) and responses compared to those from a partially exposed population in a non-endemic region (n = 14), and to a naïve population in UK (n = 12). Mean results at Day 0 prior to O. tsutsugamushi infection were 12 (95% CI 0-25) and 15 (2-27) spot-forming cells (SFC)/106 PBMC for infected and control macaques respectively. Strong O. tsutsugamushi-specific IFN-γ responses were seen post infection, with ELISpot responses 20-fold higher than baseline at Day 7 (mean 235, 95% CI 200-270 SFC/106 PBMC), 105-fold higher at Day 14 (mean 1261, 95% CI 1,097-1,425 SFC/106 PBMC), 125-fold higher at Day 21 (mean 1,498, 95% CI 1,496-1,500 SFC/106 PBMC) and 118-fold higher at Day 28

  6. Current Ebola vaccines

    Science.gov (United States)

    Hoenen, Thomas; Groseth, Allison; Feldmann, Heinz

    2012-01-01

    Introduction Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates, with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. However, a number of vaccine candidates have been developed in the last decade that are highly protective in non-human primates, the gold standard animal model for Ebola hemorrhagic fever. Areas covered This review analyzes a number of scenarios for the use of ebolavirus vaccines, discusses the requirements for ebolavirus vaccines in these scenarios, and describes current ebolavirus vaccines. Among these vaccines are recombinant Adenoviruses, recombinant Vesicular Stomatitis viruses, recombinant Human Parainfluenza viruses and virus-like particles. Interestingly, one of these vaccine platforms, based on recombinant Vesicular Stomatitis viruses, has also demonstrated post-exposure protection in non-human primates. Expert opinion The most pressing remaining challenge is now to move these vaccine candidates forward into human trials and towards licensure. In order to achieve this, it will be necessary to establish the mechanisms and correlates of protection for these vaccines, and to continue to demonstrate their safety, particularly in potentially immunocompromised populations. However, already now there is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible. PMID:22559078

  7. Vaccines in a hurry.

    Science.gov (United States)

    Søborg, Christian; Mølbak, Kåre; Doherty, T Mark; Ulleryd, Peter; Brooks, Tim; Coenen, Claudine; van der Zeijst, Ben

    2009-05-26

    Preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. The development, production and application of emergency vaccinations are the important measures against such threats. Vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the Spanish flu, the polio epidemics in the 1950s, or the SARS outbreak in 2003 if its spread had not been contained in time. Given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. However, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. In the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in Europe by focusing on public-private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies.

  8. Vaccine strategies: Optimising outcomes.

    Science.gov (United States)

    Hardt, Karin; Bonanni, Paolo; King, Susan; Santos, Jose Ignacio; El-Hodhod, Mostafa; Zimet, Gregory D; Preiss, Scott

    2016-12-20

    Successful immunisation programmes generally result from high vaccine effectiveness and adequate uptake of vaccines. In the development of new vaccination strategies, the structure and strength of the local healthcare system is a key consideration. In high income countries, existing infrastructures are usually used, while in less developed countries, the capacity for introducing new vaccines may need to be strengthened, particularly for vaccines administered beyond early childhood, such as the measles or human papillomavirus (HPV) vaccine. Reliable immunisation service funding is another important factor and low income countries often need external supplementary sources of finance. Many regions also obtain support in generating an evidence base for vaccination via initiatives created by organisations including World Health Organization (WHO), the Pan American Health Organization (PAHO), the Agence de Médecine Préventive and the Sabin Vaccine Institute. Strong monitoring and surveillance mechanisms are also required. An example is the efficient and low-cost approaches for measuring the impact of the hepatitis B control initiative and evaluating achievement of goals that have been established in the WHO Western Pacific region. A review of implementation strategies reveals differing degrees of success. For example, in the Americas, PAHO advanced a measles-mumps-rubella vaccine strategy, targeting different population groups in mass, catch-up and follow-up vaccination campaigns. This has had much success but coverage data from some parts of the region suggest that children are still not receiving all appropriate vaccines, highlighting problems with local service infrastructures. Stark differences in coverage levels are also observed among high income countries, as is the case with HPV vaccine implementation in the USA versus the UK and Australia, reflecting differences in delivery settings. Experience and research have shown which vaccine strategies work well and the

  9. The Meningitis Vaccine Project.

    Science.gov (United States)

    LaForce, F Marc; Konde, Kader; Viviani, Simonetta; Préziosi, Marie-Pierre

    2007-09-03

    Epidemic meningococcal meningitis is an important public health problem in sub-Saharan Africa. Current control measures rely on reactive immunizations with polysaccharide (PS) vaccines that do not induce herd immunity and are of limited effectiveness in those under 2 years of age. Conversely, polysaccharide conjugate vaccines are effective in infants and have consistently shown an important effect on decreasing carriage, two characteristics that facilitate disease control. In 2001 the Meningitis Vaccine Project (MVP) was created as a partnership between PATH and the World Health Organization (WHO) with the goal of eliminating meningococcal epidemics in Africa through the development, licensure, introduction, and widespread use of conjugate meningococcal vaccines. Since group A Neisseria meningitidis (N. meningitidis) is the dominant pathogen causing epidemic meningitis in Africa MVP is developing an affordable (US$ 0.40 per dose) meningococcal A (Men A) conjugate vaccine through an innovative international partnership that saw transfer of a conjugation and fermentation technology to a developing country vaccine manufacturer. A Phase 1 study of the vaccine in India has shown that the product is safe and immunogenic. Phase 2 studies have begun in Africa, and a large demonstration study of the conjugate vaccine is envisioned for 2008-2009. After extensive consultations with African public health officials a vaccine introduction plan has been developed that includes introduction of the Men A conjugate vaccine into standard Expanded Programme on Immunization (EPI) schedules but also emphasizes mass vaccination of 1-29 years old to induce herd immunity, a strategy that has been shown to be highly effective when the meningococcal C (Men C) conjugate vaccine was introduced in several European countries. The MVP model is a clear example of the usefulness of a "push mechanism" to finance the development of a needed vaccine for the developing world.

  10. 75 FR 48706 - Proposed Vaccine Information Materials for Rotavirus Vaccine

    Science.gov (United States)

    2010-08-11

    ... Vaccine Information Materials for Rotavirus Vaccine AGENCY: Centers for Disease Control and Prevention... information materials for rotavirus vaccine. DATES: Written comments are invited and must be received on or... (chickenpox), pneumococcal conjugate, rotavirus, hepatitis A, meningococcal, human papillomavirus (HPV), and...

  11. Vaccine process technology.

    Science.gov (United States)

    Josefsberg, Jessica O; Buckland, Barry

    2012-06-01

    The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory

  12. Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir.

    Science.gov (United States)

    Avalos, Claudia R; Abreu, Celina M; Queen, Suzanne E; Li, Ming; Price, Sarah; Shirk, Erin N; Engle, Elizabeth L; Forsyth, Ellen; Bullock, Brandon T; Mac Gabhann, Feilim; Wietgrefe, Stephen W; Haase, Ashley T; Zink, M Christine; Mankowski, Joseph L; Clements, Janice E; Gama, Lucio

    2017-08-15

    A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir. Using a simian immunodeficiency virus (SIV)/macaque model for HIV encephalitis and AIDS, we evaluated whether infected cells persist in brain despite ART. Eight SIV-infected pig-tailed macaques were virally suppressed with ART, and plasma and CSF viremia levels were analyzed longitudinally. To assess whether virus persisted in brain macrophages (BrMΦ) in these macaques, we used a macrophage quantitative viral outgrowth assay (MΦ-QVOA), PCR, and in situ hybridization (ISH) to measure the frequency of infected cells and the levels of viral RNA and DNA in brain. Viral RNA in brain tissue of suppressed macaques was undetectable, although viral DNA was detected in all animals. The MΦ-QVOA demonstrated that the majority of suppressed animals contained latently infected BrMΦ. We also showed that virus produced in the MΦ-QVOAs was replication competent, suggesting that latently infected BrMΦ are capable of reestablishing productive infection upon treatment interruption. This report provides the first confirmation of the presence of replication-competent SIV in BrMΦ of ART-suppressed macaques and suggests that the highly debated issue of viral latency in macrophages, at least in brain, has been addressed in SIV-infected macaques treated with ART. IMPORTANCE Resting CD4 + T cells are currently the only cells that fit the definition of a latent reservoir. However, recent evidence suggests that HIV

  13. An intravaginal ring that releases the NNRTI MIV-150 reduces SHIV transmission in macaques.

    Science.gov (United States)

    Singer, Rachel; Mawson, Paul; Derby, Nina; Rodriguez, Aixa; Kizima, Larisa; Menon, Radhika; Goldman, Daniel; Kenney, Jessica; Aravantinou, Meropi; Seidor, Samantha; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Fernández-Romero, José A; Robbiani, Melissa; Zydowsky, Thomas M

    2012-09-05

    Microbicides may prevent HIV and sexually transmitted infections (STIs) in women; however, determining the optimal means of delivery of active pharmaceutical ingredients remains a major challenge. We previously demonstrated that a vaginal gel containing the non-nucleoside reverse transcriptase inhibitor MIV-150 partially protected macaques from SHIV-RT (simian/HIV reverse transcriptase) infection, and the addition of zinc acetate rendered the gel significantly protective. We test the activity of MIV-150 without the addition of zinc acetate when delivered from either ethylene vinyl acetate (EVA) or silicone intravaginal rings (IVRs). MIV-150 was successfully delivered, because it was detected in vaginal fluids and tissues by radioimmunoassay in pharmacokinetic studies. Moreover, EVA IVRs significantly protected macaques from SHIV-RT infection. Our results demonstrate that MIV-150-containing IVRs have the potential to prevent HIV infection and highlight the possible use of IVRs for delivering drugs that block HIV and other STIs.

  14. High resolution karyotype of Thai crab-eating macaque (Macaca fascicularis

    Directory of Open Access Journals (Sweden)

    Fan Xiaobo

    2014-01-01

    Full Text Available Comparative chromosome banding analysis and/or fluorescence in situ hybridization (FISH studies are established approaches to compare human and ape chromosomes. FISH banding is a relatively new and not routinely applied method very well suited to provide to a better understanding of the evolutionary history of primate and human phylogeny. Here multicolor banding (MCB-applying probes derived from Homo sapiens were used to analyze the chromosomes of Thai crab-eating macaque (Macaca fascicularis. The results agree with those of previous studies in other macaques, e.g. Macaca sylvanus or Macaca nemestrina. This result highlights that morphological differences within the Cercopithecoidea must be found rather in subchromosomal changes or even in epigenetics than in gross structural alterations.

  15. Do infant Japanese macaques ( Macaca fuscata) categorize objects without specific training?

    Science.gov (United States)

    Murai, Chizuko; Tomonaga, Masaki; Kamegai, Kimi; Terazawa, Naoko; Yamaguchi, Masami K

    2004-01-01

    In the present study, we examined whether infant Japanese macaques categorize objects without any training, using a similar technique also used with human infants (the paired-preference method). During the familiarization phase, subjects were presented twice with two pairs of different objects from one global-level category. During the test phase, they were presented twice with a pair consisting of a novel familiar-category object and a novel global-level category object. The subjects were tested with three global-level categories (animal, furniture, and vehicle). It was found that they showed significant novelty preferences as a whole, indicating that they processed similarities between familiarization objects and novel familiar-category objects. These results suggest that subjects responded distinctively to objects without training, indicating the possibility that infant macaques possess the capacity for categorization.

  16. Temporal Lobe Lesions and Perception of Species-Specific Vocalizations by Macaques

    Science.gov (United States)

    Heffner, Henry E.; Heffner, Rickye S.

    1984-10-01

    Japanese macaques were trained to discriminate two forms of their coo vocalization before and after unilateral and bilateral ablation of the temporal cortex. Unilateral ablation of the left superior temporal gyrus, including auditory cortex, resulted in an initial impairment in the discrimination, but similar unilateral ablation of the right superior temporal gyrus had no effect. Bilateral temporal lesions including auditory cortex completely abolished the ability of the animals to discriminate their coos. Neither unilateral nor bilateral ablation of cortex dorsal to and sparing the auditory cortex had any effect on the discrimination. The perception of species-specific vocalizations by Japanese macaques seems to be mediated by the temporal cortex, with the left hemisphere playing a predominant role.

  17. Macaque cardiac physiology is sensitive to the valence of passively viewed sensory stimuli.

    Directory of Open Access Journals (Sweden)

    Eliza Bliss-Moreau

    Full Text Available Autonomic nervous system activity is an important component of affective experience. We demonstrate in the rhesus monkey that both the sympathetic and parasympathetic branches of the autonomic nervous system respond differentially to the affective valence of passively viewed video stimuli. We recorded cardiac impedance and an electrocardiogram while adult macaques watched a series of 300 30-second videos that varied in their affective content. We found that sympathetic activity (as measured by cardiac pre-ejection period increased and parasympathetic activity (as measured by respiratory sinus arrhythmia decreased as video content changes from positive to negative. These findings parallel the relationship between autonomic nervous system responsivity and valence of stimuli in humans. Given the relationship between human cardiac physiology and affective processing, these findings suggest that macaque cardiac physiology may be an index of affect in nonverbal animals.

  18. Vocal tract length and formant frequency dispersion correlate with body size in rhesus macaques.

    Science.gov (United States)

    Fitch, W T

    1997-08-01

    Body weight, length, and vocal tract length were measured for 23 rhesus macaques (Macaca mulatta) of various sizes using radiographs and computer graphic techniques. linear predictive coding analysis of tape-recorded threat vocalizations were used to determine vocal tract resonance frequencies ("formants") for the same animals. A new acoustic variable is proposed, "formant dispersion," which should theoretically depend upon vocal tract length. Formant dispersion is the averaged difference between successive formant frequencies, and was found to be closely tied to both vocal tract length and body size. Despite the common claim that voice fundamental frequency (F0) provides an acoustic indication of body size, repeated investigations have failed to support such a relationship in many vertebrate species including humans. Formant dispersion, unlike voice pitch, is proposed to be a reliable predictor of body size in macaques, and probably many other species.

  19. Radiographic measurement of the cardiothoracic ratio in pet macaques from Sulawesi, Indonesia

    Energy Technology Data Exchange (ETDEWEB)

    Schillaci, Michael A. [Department of Social Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4 (Canada)], E-mail: schillaci@utsc.utoronto.ca; Parish, Stephanie [Department of Social Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4 (Canada); Jones-Engel, Lisa [National Primate Research Center, University of Washington, 1705 N.E. Pacific Street, Seattle, WA 98195 (United States)

    2009-11-15

    The relative size of the heart, as measured by the cardiothoracic ratio, is often used as an index of ventricular hypertrophy-an important measure of myocardial pathophysiology in human primates. Despite its widespread use in human medicine, use of the cardiothoracic ratio in nonhuman primate veterinary medicine has been poorly documented. This report describes the results of our radiographic study of the cardiothoracic ratio in a sample of pet monkeys from Sulawesi, Indonesia. We assessed the effects of age and sex on cardiothoracic ratios, and compared our estimates with those presented in the literature for the Formosan macaque (Macaca cyclopis). Our results indicated a significant difference between the Sulawesi macaque species groupings in cardiothoracic ratios. Sex and age-related differences were not significant. Comparisons of cardiothoracic ratios with published ratios indicated similarity between M. cyclopis and Macaca nigra, but not between M. cyclopis and Macaca tonkeana.

  20. Radiographic measurement of the cardiothoracic ratio in pet macaques from Sulawesi, Indonesia

    International Nuclear Information System (INIS)

    Schillaci, Michael A.; Parish, Stephanie; Jones-Engel, Lisa

    2009-01-01

    The relative size of the heart, as measured by the cardiothoracic ratio, is often used as an index of ventricular hypertrophy-an important measure of myocardial pathophysiology in human primates. Despite its widespread use in human medicine, use of the cardiothoracic ratio in nonhuman primate veterinary medicine has been poorly documented. This report describes the results of our radiographic study of the cardiothoracic ratio in a sample of pet monkeys from Sulawesi, Indonesia. We assessed the effects of age and sex on cardiothoracic ratios, and compared our estimates with those presented in the literature for the Formosan macaque (Macaca cyclopis). Our results indicated a significant difference between the Sulawesi macaque species groupings in cardiothoracic ratios. Sex and age-related differences were not significant. Comparisons of cardiothoracic ratios with published ratios indicated similarity between M. cyclopis and Macaca nigra, but not between M. cyclopis and Macaca tonkeana.

  1. Vaccination against seasonal flu

    CERN Multimedia

    2015-01-01

    The Medical Service once again recommends you to get your annual flu vaccination for the year.   Vaccination is the most effective way of avoiding the illness and any serious consequences and protecting those around you. The flu can have especially serious consequences for people with chronic conditions (diabetes, cardio-vascular disease, etc.), pregnant women, infants, and people over 65 years of age. Remember, anyone working on the CERN site who wishes to be vaccinated against seasonal flu should go to the Infirmary (Building 57, ground floor) with their vaccine. The Medical Service will issue a prescription on the day of the vaccination for the purposes of reimbursement by UNIQA. NB: The Medical Service cannot provide this vaccination service for family members or retired members of the personnel. For more information: • The "Seasonal flu" flyer by the Medical Service • Recommendations of the Swiss Federal Office of Public...

  2. Prophylactic Hepatitis E Vaccine.

    Science.gov (United States)

    Zhang, Jun; Zhao, Qinjian; Xia, Ningshao

    2016-01-01

    Hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection-associated damage or death include pregnant women, patients with basic liver diseases, and elderly persons. Vaccine would be the most effective means for prevention of HEV infection. The lack of an efficient cell culture system for HEV makes the development of classic inactive or attenuated vaccine infeasible. Hence, the recombinant vaccine approaches are explored deeply. The neutralizing sites are located almost exclusively in the capsid protein, pORF2, of the virion. Based on pORF2, many vaccine candidates showed potential of protecting primate animals; two of them were tested in human and evidenced to be well tolerated in adults and highly efficacious in preventing hepatitis E. The world's first hepatitis E vaccine, Hecolin ® (HEV 239 vaccine), was licensed in China and launched in 2012.

  3. Vaccination and neurological disorders

    Directory of Open Access Journals (Sweden)

    Anastasia Gkampeta

    2015-12-01

    Full Text Available Active immunization of children has been proven very effective in elimination of life threatening complications of many infectious diseases in developed countries. However, as vaccination-preventable infectious diseases and their complications have become rare, the interest focuses on immunization-related adverse reactions. Unfortunately, fear of vaccination-related adverse effects can led to decreased vaccination coverage and subsequent epidemics of infectious diseases. This review includes reports about possible side effects following vaccinations in children with neurological disorders and also published recommendations about vaccinating children with neurological disorders. From all international published data anyone can conclude that vaccines are safer than ever before, but the challenge remains to convey this message to society.

  4. Vaccines and Kawasaki disease.

    Science.gov (United States)

    Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola

    2016-01-01

    The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.

  5. Vaccine development for syphilis.

    Science.gov (United States)

    Lithgow, Karen V; Cameron, Caroline E

    2017-01-01

    Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a globally prevalent disease despite remaining susceptible to penicillin treatment. Syphilis vaccine development is a viable preventative approach that will serve to complement public health-oriented syphilis prevention, screening and treatment initiatives to deliver a two-pronged approach to stemming disease spread worldwide. Areas covered: This article provides an overview of the need for development of a syphilis vaccine, summarizes significant information that has been garnered from prior syphilis vaccine studies, discusses the critical aspects of infection that would have to be targeted by a syphilis vaccine, and presents the current understanding within the field of the correlates of protection needed to be achieved through vaccination. Expert commentary: Syphilis vaccine development should be considered a priority by industry, regulatory and funding agencies, and should be appropriately promoted and supported.

  6. The Latest in Vaccine Policies: Selected Issues in School Vaccinations, Healthcare Worker Vaccinations, and Pharmacist Vaccination Authority Laws.

    Science.gov (United States)

    Barraza, Leila; Schmit, Cason; Hoss, Aila

    2017-03-01

    This paper discusses recent changes to state legal frameworks for mandatory vaccination in the context of school and healthcare worker vaccination. It then discusses state laws that allow pharmacists the authority to vaccinate.

  7. Needle-free influenza vaccination

    NARCIS (Netherlands)

    Amorij, Jean-Pierre; Hinrichs, Wouter L.J.; Frijlink, Henderik W.; Wilschut, Jan C.; Huckriede, Anke

    2010-01-01

    Vaccination is the cornerstone of influenza control in epidemic and pandemic situations. Influenza vaccines are typically given by intramuscular injection. However, needle-free vaccinations could offer several distinct advantages over intramuscular injections: they are pain-free, easier to

  8. What Vaccines Do You Need?

    Science.gov (United States)

    ... Recommendations Why Immunize? Vaccines: The Basics The Adult Vaccine Quiz Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Vaccines are recommended for adults based on age, health ...

  9. Recommended Vaccines for Healthcare Workers

    Science.gov (United States)

    ... Vaccination Resources for Healthcare Professionals Recommended Vaccines for Healthcare Workers Recommend on Facebook Tweet Share Compartir On ... for More Information Resources for Those Vaccinating HCWs Healthcare workers (HCWs) are at risk for exposure to ...

  10. Prior Exposure to Zika Virus Significantly Enhances Peak Dengue-2 Viremia in Rhesus Macaques

    OpenAIRE

    George, Jeffy; Valiant, William G.; Mattapallil, Mary J.; Walker, Michelle; Huang, Yan-Jang S.; Vanlandingham, Dana L.; Misamore, John; Greenhouse, Jack; Weiss, Deborah E.; Verthelyi, Daniela; Higgs, Stephen; Andersen, Hanne; Lewis, Mark G.; Mattapallil, Joseph J.

    2017-01-01

    Structural and functional homologies between the Zika and Dengue viruses? envelope proteins raise the possibility that cross-reactive antibodies induced following Zika virus infection might enhance subsequent Dengue infection. Using the rhesus macaque model we show that prior infection with Zika virus leads to a significant enhancement of Dengue-2 viremia that is accompanied by neutropenia, lympocytosis, hyperglycemia, and higher reticulocyte counts, along with the activation of pro-inflammat...

  11. PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis.

    Directory of Open Access Journals (Sweden)

    Philana Ling Lin

    2016-07-01

    Full Text Available Mycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. Among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis. Here, functional imaging with 18F-fluorodeoxygluose positron emission tomography and computed tomography (PET CT of cynomolgus macaques with latent M. tuberculosis infection was used to characterize the features of reactivation after tumor necrosis factor (TNF neutralization and determine which imaging characteristics before TNF neutralization distinguish reactivation risk. PET CT was performed on latently infected macaques (n = 26 before and during the course of TNF neutralization and a separate set of latently infected controls (n = 25. Reactivation occurred in 50% of the latently infected animals receiving TNF neutralizing antibody defined as development of at least one new granuloma in adjacent or distant locations including extrapulmonary sites. Increased lung inflammation measured by PET and the presence of extrapulmonary involvement before TNF neutralization predicted reactivation with 92% sensitivity and specificity. To define the biologic features associated with risk of reactivation, we used these PET CT parameters to identify latently infected animals at high risk for reactivation. High risk animals had higher cumulative lung bacterial burden and higher maximum lesional bacterial burdens, and more T cells producing IL-2, IL-10 and IL-17 in lung granulomas as compared to low risk macaques. In total, these data support that risk of reactivation is associated with lung inflammation and higher bacterial burden in macaques with latent Mtb infection.

  12. Plasmid-Mediated Quinolone Resistance in Shigella flexneri Isolated From Macaques

    Directory of Open Access Journals (Sweden)

    Anthony J. Mannion

    2018-03-01

    Full Text Available Non-human primates (NHPs for biomedical research are commonly infected with Shigella spp. that can cause acute dysentery or chronic episodic diarrhea. These animals are often prophylactically and clinically treated with quinolone antibiotics to eradicate these possible infections. However, chromosomally- and plasmid-mediated antibiotic resistance has become an emerging concern for species in the family Enterobacteriaceae. In this study, five individual isolates of multi-drug resistant Shigella flexneri were isolated from the feces of three macaques. Antibiotic susceptibility testing confirmed resistance or decreased susceptibility to ampicillin, amoxicillin-clavulanic acid, cephalosporins, gentamicin, tetracycline, ciprofloxacin, enrofloxacin, levofloxacin, and nalidixic acid. S. flexneri isolates were susceptible to trimethoprim-sulfamethoxazole, and this drug was used to eradicate infection in two of the macaques. Plasmid DNA from all isolates was positive for the plasmid-encoded quinolone resistance gene qnrS, but not qnrA and qnrB. Conjugation and transformation of plasmid DNA from several S. flexneri isolates into antibiotic-susceptible Escherichia coli strains conferred the recipients with resistance or decreased susceptibility to quinolones and beta-lactams. Genome sequencing of two representative S. flexneri isolates identified the qnrS gene on a plasmid-like contig. These contigs showed >99% homology to plasmid sequences previously characterized from quinolone-resistant Shigella flexneri 2a and Salmonella enterica strains. Other antibiotic resistance genes and virulence factor genes were also identified in chromosome and plasmid sequences in these genomes. The findings from this study indicate macaques harbor pathogenic S. flexneri strains with chromosomally- and plasmid-encoded antibiotic resistance genes. To our knowledge, this is the first report of plasmid-mediated quinolone resistance in S. flexneri isolated from NHPs and warrants

  13. Directed shift of vaginal microbiota induced by vaginal application of sucrose gel in rhesus macaques

    OpenAIRE

    Hu, Kai-tao; Zheng, Jin-xin; Yu, Zhi-jian; Chen, Zhong; Cheng, Hang; Pan, Wei-guang; Yang, Wei-zhi; Wang, Hong-yan; Deng, Qi-wen; Zeng, Zhong-ming

    2015-01-01

    Objectives: Sucrose gel was used to treat bacterial vaginosis in a phase III clinical trial. However, the changes of vaginal flora after treatment were only examined by Nugent score in that clinical trial, While the vaginal microbiota of rhesus macaques is characterized by anaerobic, Gram-negative bacteria, few lactobacilli, and pH levels above 4.6, similar to the microbiota of patients with bacterial vaginosis. This study is aimed to investigate the change of the vaginal microbiota of rehsus...

  14. Vocalizations during post-conflict affiliations from victims toward aggressors based on uncertainty in Japanese macaques.

    Science.gov (United States)

    Katsu, Noriko; Yamada, Kazunori; Nakamichi, Masayuki

    2017-01-01

    We investigated the use of vocalizations called "grunts," "girneys," and "coos" accompanied by post-conflict affiliative interaction between former opponents (reconciliation) in Japanese macaques (Macaca fuscata). Although reconciliation functions to repair bonds, such interactions sometimes entail risks of receiving further aggression. Vocalizations can be used at a distance from the former opponent; thus, we predict that vocalizations are used particularly by victims of a conflict, and are frequently used in situations of uncertainty when it is difficult for them to estimate whether the former opponent will resume aggression. In addition, we predict that vocalizations are effective in preventing further aggression. To test these hypotheses, we conducted observations of post-conflict and matched-control situations in female Japanese macaques living in a free-ranging group. We found that former opponents tended to be attracted to each other within the first minute following a conflict, thus demonstrating reconciliation behavior. Vocalizations were more frequently used by the victims in post-conflict interactions than under control situations; however, this tendency was not found in aggressors. When affiliation with the former opponent occurred, victims were more likely to use vocalizations towards less familiar opponents. These findings suggest that Japanese macaques used vocalizations more often when interacting with less predictable former opponents. Victims were more likely to receive aggression from former aggressors when engaged in affiliations with them than under no such affiliations. No significant differences were found in the probability of the victims receiving aggression, regardless of whether they used vocalizations; thus, whether the victim benefits from using vocalizations in these contexts remains unclear. Japanese macaques form despotic societies and therefore, further aggression was inevitable, to some degree, after a conflict. The use of

  15. Vocalizations during post-conflict affiliations from victims toward aggressors based on uncertainty in Japanese macaques.

    Directory of Open Access Journals (Sweden)

    Noriko Katsu

    Full Text Available We investigated the use of vocalizations called "grunts," "girneys," and "coos" accompanied by post-conflict affiliative interaction between former opponents (reconciliation in Japanese macaques (Macaca fuscata. Although reconciliation functions to repair bonds, such interactions sometimes entail risks of receiving further aggression. Vocalizations can be used at a distance from the former opponent; thus, we predict that vocalizations are used particularly by victims of a conflict, and are frequently used in situations of uncertainty when it is difficult for them to estimate whether the former opponent will resume aggression. In addition, we predict that vocalizations are effective in preventing further aggression. To test these hypotheses, we conducted observations of post-conflict and matched-control situations in female Japanese macaques living in a free-ranging group. We found that former opponents tended to be attracted to each other within the first minute following a conflict, thus demonstrating reconciliation behavior. Vocalizations were more frequently used by the victims in post-conflict interactions than under control situations; however, this tendency was not found in aggressors. When affiliation with the former opponent occurred, victims were more likely to use vocalizations towards less familiar opponents. These findings suggest that Japanese macaques used vocalizations more often when interacting with less predictable former opponents. Victims were more likely to receive aggression from former aggressors when engaged in affiliations with them than under no such affiliations. No significant differences were found in the probability of the victims receiving aggression, regardless of whether they used vocalizations; thus, whether the victim benefits from using vocalizations in these contexts remains unclear. Japanese macaques form despotic societies and therefore, further aggression was inevitable, to some degree, after a conflict

  16. Distribution of glutamatergic, GABAergic, and glycinergic neurons in the auditory pathways of macaque monkeys.

    Science.gov (United States)

    Ito, T; Inoue, K; Takada, M

    2015-12-03

    Macaque monkeys use complex communication calls and are regarded as a model for studying the coding and decoding of complex sound in the auditory system. However, little is known about the distribution of excitatory and inhibitory neurons in the auditory system of macaque monkeys. In this study, we examined the overall distribution of cell bodies that expressed mRNAs for VGLUT1, and VGLUT2 (markers for glutamatergic neurons), GAD67 (a marker for GABAergic neurons), and GLYT2 (a marker for glycinergic neurons) in the auditory system of the Japanese macaque. In addition, we performed immunohistochemistry for VGLUT1, VGLUT2, and GAD67 in order to compare the distribution of proteins and mRNAs. We found that most of the excitatory neurons in the auditory brainstem expressed VGLUT2. In contrast, the expression of VGLUT1 mRNA was restricted to the auditory cortex (AC), periolivary nuclei, and cochlear nuclei (CN). The co-expression of GAD67 and GLYT2 mRNAs was common in the ventral nucleus of the lateral lemniscus (VNLL), CN, and superior olivary complex except for the medial nucleus of the trapezoid body, which expressed GLYT2 alone. In contrast, the dorsal nucleus of the lateral lemniscus, inferior colliculus, thalamus, and AC expressed GAD67 alone. The absence of co-expression of VGLUT1 and VGLUT2 in the medial geniculate, medial superior olive, and VNLL suggests that synaptic responses in the target neurons of these nuclei may be different between rodents and macaque monkeys. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Speech-like orofacial oscillations in stump-tailed macaque (Macaca arctoides) facial and vocal signals.

    Science.gov (United States)

    Toyoda, Aru; Maruhashi, Tamaki; Malaivijitnond, Suchinda; Koda, Hiroki

    2017-10-01

    Speech is unique to humans and characterized by facial actions of ∼5 Hz oscillations of lip, mouth or jaw movements. Lip-smacking, a facial display of primates characterized by oscillatory actions involving the vertical opening and closing of the jaw and lips, exhibits stable 5-Hz oscillation patterns, matching that of speech, suggesting that lip-smacking is a precursor of speech. We tested if facial or vocal actions exhibiting the same rate of oscillation are found in wide forms of facial or vocal displays in various social contexts, exhibiting diversity among species. We observed facial and vocal actions of wild stump-tailed macaques (Macaca arctoides), and selected video clips including facial displays (teeth chattering; TC), panting calls, and feeding. Ten open-to-open mouth durations during TC and feeding and five amplitude peak-to-peak durations in panting were analyzed. Facial display (TC) and vocalization (panting) oscillated within 5.74 ± 1.19 and 6.71 ± 2.91 Hz, respectively, similar to the reported lip-smacking of long-tailed macaques and the speech of humans. These results indicated a common mechanism for the central pattern generator underlying orofacial movements, which would evolve to speech. Similar oscillations in panting, which evolved from different muscular control than the orofacial action, suggested the sensory foundations for perceptual saliency particular to 5-Hz rhythms in macaques. This supports the pre-adaptation hypothesis of speech evolution, which states a central pattern generator for 5-Hz facial oscillation and perceptual background tuned to 5-Hz actions existed in common ancestors of macaques and humans, before the emergence of speech. © 2017 Wiley Periodicals, Inc.

  18. Intergroup variation in robbing and bartering by long-tailed macaques at Uluwatu Temple (Bali, Indonesia).

    Science.gov (United States)

    Brotcorne, Fany; Giraud, Gwennan; Gunst, Noëlle; Fuentes, Agustín; Wandia, I Nengah; Beudels-Jamar, Roseline C; Poncin, Pascal; Huynen, Marie-Claude; Leca, Jean-Baptiste

    2017-10-01

    Robbing and bartering (RB) is a behavioral practice anecdotally reported in free-ranging commensal macaques. It usually occurs in two steps: after taking inedible objects (e.g., glasses) from humans, the macaques appear to use them as tokens, returning them to humans in exchange for food. While extensively studied in captivity, our research is the first to investigate the object/food exchange between humans and primates in a natural setting. During a 4-month study in 2010, we used both focal and event sampling to record 201 RB events in a population of long-tailed macaques (Macaca fascicularis), including four neighboring groups ranging freely around Uluwatu Temple, Bali (Indonesia). In each group, we documented the RB frequency, prevalence and outcome, and tested the underpinning anthropogenic and demographic determinants. In line with the environmental opportunity hypothesis, we found a positive qualitative relation at the group level between time spent in tourist zones and RB frequency or prevalence. For two of the four groups, RB events were significantly more frequent when humans were more present in the environment. We also found qualitative partial support for the male-biased sex ratio hypothesis [i.e., RB was more frequent and prevalent in groups with higher ratios of (sub)adult males], whereas the group density hypothesis was not supported. This preliminary study showed that RB is a spontaneous, customary (in some groups), and enduring population-specific practice characterized by intergroup variation in Balinese macaques. As such, RB is a candidate for a new behavioral tradition in this species.

  19. Amblyomma maculatum Feeding Augments Rickettsia parkeri Infection in a Rhesus Macaque Model: A Pilot Study

    Science.gov (United States)

    Banajee, Kaikhushroo H.; Embers, Monica E.; Langohr, Ingeborg M.; Doyle, Lara A.; Hasenkampf, Nicole R.; Macaluso, Kevin R.

    2015-01-01

    Rickettsia parkeri is an emerging eschar-causing human pathogen in the spotted fever group of Rickettsia and is transmitted by the Gulf coast tick, Amblyomma maculatum. Tick saliva has been shown to alter both the cellular and humoral components of the innate and adaptive immune systems. However, the effect of this immunomodulation on Rickettsia transmission and pathology in an immunocompetent vertebrate host has not been fully examined. We hypothesize that, by modifying the host immune response, tick feeding enhances infection and pathology of pathogenic spotted fever group Rickettsia sp. In order to assess this interaction in vivo, a pilot study was conducted using five rhesus macaques that were divided into three groups. One group was intradermally inoculated with low passage R. parkeri (Portsmouth strain) alone (n = 2) and another group was inoculated during infestation by adult, R. parkeri-free A. maculatum (n = 2). The final macaque was infested with ticks alone (tick feeding control group). Blood, lymph node and skin biopsies were collected at several time points post-inoculation/infestation to assess pathology and quantify rickettsial DNA. As opposed to the tick-only animal, all Rickettsia-inoculated macaques developed inflammatory leukograms, elevated C-reactive protein concentrations, and elevated TH1 (interferon-γ, interleukin-15) and acute phase inflammatory cytokines (interleukin-6) post-inoculation, with greater neutrophilia and interleukin-6 concentrations in the tick plus R. parkeri group. While eschars formed at all R. parkeri inoculation sites, larger and slower healing eschars were observed in the tick feeding plus R. parkeri group. Furthermore, dissemination of R. parkeri to draining lymph nodes early in infection and increased persistence at the inoculation site were observed in the tick plus R. parkeri group. This study indicates that rhesus macaques can be used to model R. parkeri rickettsiosis, and suggests that immunomodulatory factors

  20. Social object play among young Japanese macaques (Macaca fuscata) in Arashiyama, Japan.

    Science.gov (United States)

    Shimada, Masaki

    2006-10-01

    Social object play (SOP), i.e., social play using portable object(s), among young Japanese macaques (Macaca fuscata; 0-4 years old) in the Arashiyama E troop was studied using a modified sequence sampling method from July to October 2000. SOP was a relatively common activity for most of the young macaques and often continued for long periods. Participants used many kinds of object, including edible natural objects and artificial objects, such as plastic bottles, but they never used provisioned food or wild fruit in SOP bouts. An analysis of long bouts (>/=0.5 min) revealed the following interactive SOP features: (1) at any given time, participants used only one object, and only one participant held the object; (2) during SOP play-chasing, the object holder was likely to be chased by others; (3) during long bouts, the object changed hands frequently; and (4) agonistic competition for an object among young macaques was rare. Combinations of sexes, ages, relative ranks, or matrilines of the object holder and non-holder did not affect the tendency that the holder was chased by non-holder(s) during play-chasing. Even when there was a change in object holders, the repetitiveness of this interactive pattern, i.e., that the holder would be chased during SOP bouts, distinguished the SOP structure from that of other types of social play without object(s). General proximate social play mechanisms, such as self-handicapping or role taking, were associated with SOP. Other mechanisms that affected SOP included the following: (1) young macaques treated an object as a target in play competition, and (2) 'being the holder of a target object' was associated with the 'role of the chasee.'

  1. Dynamic Interaction of Enterovirus 71 and Dendritic Cells in Infected Neonatal Rhesus Macaques.

    Science.gov (United States)

    Zhao, Ting; Zhang, Zhixiao; Zhang, Ying; Feng, Min; Fan, Shengtao; Wang, Lichun; Liu, Longding; Wang, Xi; Wang, Qinglin; Zhang, Xiaolong; Wang, Jingjing; Liao, Yun; He, Zhanlong; Lu, Shuaiyao; Yang, Huai; Li, Qihan

    2017-01-01

    Enterovirus 71 (EV71) is one of the main pathogens responsible for hand, foot, and mouth disease (HFMD). Infection with EV71 can lead to severe clinical disease via extensive infections of either the respiratory or alimentary tracts in children. Based on the previous pathological study of EV71 infections in neonatal rhesus macaques, our work using this animal model and an EV71 chimera that expresses enhanced green fluorescent protein (EGFP-EV71) primarily explored where EV71 localizes and proliferates, and the subsequent initiation of the pathological process. The chimeric EGFP-EV71 we constructed was similar to the wild-type EV71 (WT-EV71) virus in its biological characteristics. Similar clinical manifestations and histo-pathologic features were equally displayed in neonatal rhesus macaques infected with either WT-EV71 or EGFP-EV71 via the respiratory route. Fluorescent signal tracing in tissues from the animals infected with EGFP-EV71 showed that EV71 proliferated primarily in the respiratory tract epithelium and the associated lymphoid tissues. Immunofluorescence and flow cytometry analyses revealed that EV71 was able to enter a pre-conventional dendritic cell (DC) population at the infection sites. The viremia identified in the macaques infected by WT-EV71 or EGFP-EV71 was present even in the artificial presence of a specific antibody against the virus. Our results suggest that EV71 primarily proliferates in the respiratory tract epithelium followed by subsequent entry into a pre-cDC population of DCs. These cells are then hijacked by the virus and they can potentially transmit the virus from local sites to other organs through the blood circulation during the infection process. Our results suggest that the EV71 infection process in this DC population does not interfere with the induction of an independent immune response against the EV71 infection in the neonatal macaques.

  2. Rotavirus vaccines and vaccination in Latin America

    Directory of Open Access Journals (Sweden)

    Linhares Alexandre C.

    2000-01-01

    Full Text Available Worldwide, rotaviruses account for more than 125 million cases of infantile gastroenteritis and nearly 1 million deaths per year, mainly in developing countries. Rather than other control measures, vaccination is most likely to have a major impact on rotavirus disease incidence. The peak incidence of rotavirus diarrhea occurs between 6 and 24 months of age. In developing countries, however, cases are not uncommon among children younger than 6 months. G serotypes 1 to 4 are responsible for most disease, but there are indications that in Brazil that G type 5 is of emerging epidemiological importance. Both homotypic and heterotypic responses are elicited during natural rotavirus infection, and the immunological response at the intestinal mucosal surface is probably the more consistent predictor of clinical immunity. With the primary objective of protecting children against life-threatening dehydrating diarrhea, many approaches to rotavirus vaccine development have been attempted. One vaccine, the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV, was given licensing approval in the United States of America, introduced to the market, and later withdrawn. A number of studies have found better efficacy of RRV-TV in developed countries than in developing ones. Field trials with a 4 X 10(4 plaque-forming units (PFU preparation of RRV-TV have been carried out in two countries in Latin America, Brazil and Peru. Those trials yielded protective efficacy rates against all rotavirus diarrhea ranging from 18% to 35%. Data from a large catchment trial in Venezuela with a higher RRV-TV dose, of 4 X 10(5 PFU/dose, indicated an efficacy rate of 48% against all rotavirus diarrhea and 88% against severe rotavirus diarrhea. It appears that breast-feeding does not compromise the efficacy of RRV-TV if three doses of the vaccine are administered. Similarly, possible interference of oral poliovirus vaccine with the "take" of the rotavirus vaccine can be

  3. Rotavirus vaccines and vaccination in Latin America

    Directory of Open Access Journals (Sweden)

    Alexandre C. Linhares

    2000-11-01

    Full Text Available Worldwide, rotaviruses account for more than 125 million cases of infantile gastroenteritis and nearly 1 million deaths per year, mainly in developing countries. Rather than other control measures, vaccination is most likely to have a major impact on rotavirus disease incidence. The peak incidence of rotavirus diarrhea occurs between 6 and 24 months of age. In developing countries, however, cases are not uncommon among children younger than 6 months. G serotypes 1 to 4 are responsible for most disease, but there are indications that in Brazil that G type 5 is of emerging epidemiological importance. Both homotypic and heterotypic responses are elicited during natural rotavirus infection, and the immunological response at the intestinal mucosal surface is probably the more consistent predictor of clinical immunity. With the primary objective of protecting children against life-threatening dehydrating diarrhea, many approaches to rotavirus vaccine development have been attempted. One vaccine, the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV, was given licensing approval in the United States of America, introduced to the market, and later withdrawn. A number of studies have found better efficacy of RRV-TV in developed countries than in developing ones. Field trials with a 4 X 10(4 plaque-forming units (PFU preparation of RRV-TV have been carried out in two countries in Latin America, Brazil and Peru. Those trials yielded protective efficacy rates against all rotavirus diarrhea ranging from 18% to 35%. Data from a large catchment trial in Venezuela with a higher RRV-TV dose, of 4 X 10(5 PFU/dose, indicated an efficacy rate of 48% against all rotavirus diarrhea and 88% against severe rotavirus diarrhea. It appears that breast-feeding does not compromise the efficacy of RRV-TV if three doses of the vaccine are administered. Similarly, possible interference of oral poliovirus vaccine with the "take" of the rotavirus vaccine can be

  4. Pricing of new vaccines

    OpenAIRE

    Lee, Bruce Y; McGlone, Sarah M

    2010-01-01

    New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following eleven components: (1) Conduct a target population analysis; (2) Map potential competitors and alternatives; (3) Construct a vaccine targe...

  5. Underutilization of Influenza Vaccine

    Directory of Open Access Journals (Sweden)

    Marshall K. Cheney

    2013-04-01

    Full Text Available Yearly influenza vaccination continues to be underutilized by those who would most benefit from it. The Health Belief Model was used to explain differences in beliefs about influenza vaccination among at-risk individuals resistant to influenza vaccination. Survey data were collected from 74 members of at-risk groups who were not vaccinated for influenza during the previous flu season. Accepting individuals were more likely to perceive flu as a threat to health and perceive access barriers, and cues to action were the most important influence on whether they plan to get vaccinated. In comparison, resistant individuals did not feel threatened by the flu, access barriers were not a problem, and they did not respond favorably to cues to action. Perceived threat, perceived access barriers, and cues to action were significantly associated with plans to be vaccinated for influenza in the next flu season. Participants who saw influenza as a threat to their health had 5.4 times the odds of planning to be vaccinated than those who did not. Participants reporting barriers to accessing influenza vaccination had 7.5 times the odds of reporting plans to be vaccinated. Those responding positively to cues to action had 12.2 times the odds of planning to be vaccinated in the next flu season than those who did not. Accepting and resistant individuals have significant differences in their beliefs, which require different intervention strategies to increase vaccination rates. These findings provide important information to researchers and practitioners working to increase influenza vaccination rates.

  6. Respiratory Syncytial Virus Vaccines

    OpenAIRE

    Dudas, Robert A.; Karron, Ruth A.

    1998-01-01

    Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness (LRI) in infants and children worldwide and causes significant LRI in the elderly and in immunocompromised patients. The goal of RSV vaccination is to prevent serious RSV-associated LRI. There are several obstacles to the development of successful RSV vaccines, including the need to immunize very young infants, who may respond inadequately to vaccination; the existence of two antigenically d...

  7. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

    Science.gov (United States)

    Chang, W L William; Gonzalez, Denise F; Kieu, Hung T; Castillo, Luis D; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D; Shacklett, Barbara L; Barry, Peter A; Sparger, Ellen E

    2017-01-01

    Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease.

  8. Fading Perceptual Resemblance: A Path for Rhesus Macaques (Macaca mulatta) to Conceptual Matching?

    Science.gov (United States)

    Smith, J. David; Flemming, Timothy M.; Boomer, Joseph; Beran, Michael J.; Church, Barbara A.

    2013-01-01

    Cognitive, comparative, and developmental psychologists have long been intrigued by humans’ and animals’ capacity to respond to abstract relations like sameness and difference, because this capacity may underlie crucial aspects of cognition like analogical reasoning. Recently, this capacity has been explored in higher-order, relational matching-to-sample (RMTS) tasks in which humans and animals try to complete analogies of sameness and difference between disparate groups of items. The authors introduced a new paradigm to this area, by yoking the relational-matching cue to a perceptual-matching cue. Then, using established algorithms for shape distortion, the perceptual cue was weakened and eliminated. Humans’ RMTS performance easily transcended the elimination of perceptual support. In contrast, RMTS performance by six macaques faltered as they were weaned from perceptual support. No macaque showed evidence of mature RMTS performance, even given more than 260,000 training trials during which we tried to coax a relational-matching performance from them. It is an important species difference that macaques show so hesitant a response to conceptual relations when humans respond to them so effortlessly. It raises theoretical questions about the emergence of this crucial capacity during humans’ cognitive evolution and during humans’ cognitive development. PMID:24076537

  9. A comparative study of middle cerebral pressure in dogs and macaques

    Science.gov (United States)

    Symon, Lindsay

    1967-01-01

    1. A comparison has been made of the pressures recorded from pial branches of the middle cerebral artery in dogs and macaques. This pressure has been shown to be between 88 and 95% of femoral arterial pressure in dogs under chloralose anaesthesia, and between 80 and 90% of femoral arterial pressure in macaques similarly anaesthetized. 2. The effect of occlusion of the main vessels in the neck is shown to differ considerably in the two species. Blood pressure within the forebrain of the dog is shown to be largely dependent upon the integrity of the external carotid artery, whereas in the monkey the external carotid artery is without effect in the maintenance of forebrain blood pressure. Occlusion of the four major arteries in the neck is shown to produce a greater effect in the macaque and to be accompanied by signs of medullary ischaemia in this species. 3. After occlusion of the main middle cerebral artery, arterial pressure measured distal to the occlusion depends upon the integrity of collateral vessels from the other cerebral arteries. When only a branch of the middle cerebral artery is occluded, the greater part of the residual blood pressure depends upon anastomoses from other branches of the middle cerebral artery itself. ImagesFig. 1 PMID:4963869

  10. Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL

    Directory of Open Access Journals (Sweden)

    Maria S. Salvato

    2007-01-01

    Full Text Available Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and CD4- lymphocyte subsets in macaques contributes to viral persistence and suggests the importance of mechanisms for depleting both infected and uninfected (bystander cells. Bystander cell killing can occur when FasL binds the Fas receptor on activated lymphocytes, which include T and B cell subpopulations that are responding to the infection. Destruction of specific immune cells could be an important mechanism for blunting viral immunity and establishing persistent infection with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal antibody against FasL (RNOK203. Here we show that treatment with anti-FasL reduced cell death in circulating T and B cells, increased CTL and antibody responses to viral proteins, and lowered the setpoint viremia. By blocking FasL during only the first few weeks after infection, we attenuated SIVmac disease and increased the life span for infected and treated macaques.

  11. Acute-phase responses in healthy and diseased rhesus macaques (Macaca mulatta)

    DEFF Research Database (Denmark)

    Krogh, Anne Kirstine Havnsøe; Lundsgaard, Jo F. H.; Bakker, Jaco

    2014-01-01

    Five acute-phase reactants—serum amyloid A (SAA), C-reactive protein (CRP), haptoglobin, albumin, and iron—were measured using commercially available assays in 110 healthy rhesus macaques (Macaca mulatta), and reference intervals were established for future use in health monitoring of this species....... Reference intervals established were as follows: SAA, 29.5–87.7 mg/L; CRP, 0–17.5 mg/L; haptoglobin, 354.3–2,414.7 mg/L; albumin, 36.1–53.0 g/L; and iron, 13.3–40.2 lmol/L. Furthermore, changes in the acute-phase reactants were studied in two additional groups of animals: eight rhesus macaques suffering...... from acute traumatic injuries and nine rhesus macaques experimentally infected with Mycobacterium tuberculosis reflecting a chronic active inflammation. In animals with inflammation, SAA and haptoglobin concentrations were moderately increased, while CRP increased more than 200-fold. In addition, marked...

  12. Postexposure protection of macaques from vaginal SHIV infection by topical integrase inhibitors.

    Science.gov (United States)

    Dobard, Charles; Sharma, Sunita; Parikh, Urvi M; West, Rolieria; Taylor, Andrew; Martin, Amy; Pau, Chou-Pong; Hanson, Debra L; Lipscomb, Jonathan; Smith, James; Novembre, Francis; Hazuda, Daria; Garcia-Lerma, J Gerardo; Heneine, Walid

    2014-03-12

    Coitally delivered microbicide gels containing antiretroviral drugs are important for HIV prevention. However, to date, microbicides have contained entry or reverse transcriptase inhibitors that block early steps in virus infection and thus need to be given as a preexposure dose that interferes with sexual practices and may limit compliance. Integrase inhibitors block late steps after virus infection and therefore are more suitable for post-coital dosing. We first determined the kinetics of strand transfer in vitro and confirmed that integration begins about 6 hours after infection. We then used a repeat-challenge macaque model to assess efficacy of vaginal gels containing integrase strand transfer inhibitors when applied before or after simian/human immunodeficiency virus (SHIV) challenge. We showed that gel containing the strand transfer inhibitor L-870812 protected two of three macaques when applied 30 min before SHIV challenge. We next evaluated the efficacy of 1% raltegravir gel and demonstrated its ability to protect macaques when applied 3 hours after SHIV exposure (five of six protected; P infections showed no evidence of drug resistance in plasma or vaginal secretions despite continued gel dosing after infection. We documented rapid vaginal absorption reflecting a short pharmacological lag time and noted that vaginal, but not plasma, virus load was substantially reduced in the breakthrough infection after raltegravir gel treatment. We provide a proof of concept that topically applied integrase inhibitors protect against vaginal SHIV infection when administered shortly before or 3 hours after virus exposure.

  13. Comparison of the vaginal environment in rhesus and cynomolgus macaques pre- and post-lactobacillus colonization.

    Science.gov (United States)

    Daggett, Gregory J; Zhao, Chunxia; Connor-Stroud, Fawn; Oviedo-Moreno, Patricia; Moon, Hojin; Cho, Michael W; Moench, Thomas; Anderson, Deborah J; Villinger, Francois

    2017-10-01

    Rhesus and cynomologus macaques are valuable animal models for the study of human immunodeficiency virus (HIV) prevention strategies. However, for such studies focused on the vaginal route of infection, differences in vaginal environment may have deterministic impact on the outcome of such prevention, providing the rationale for this study. We tested the vaginal environment of rhesus and cynomolgus macaques longitudinally to characterize the normal microflora based on Nugent scores and pH. This evaluation was extended after colonization of the vaginal space with Lactobacilli in an effort to recreate NHP models representing the healthy human vaginal environment. Nugent scores and pH differed significantly between species, although data from both species were suggestive of stable bacterial vaginosis. Colonization with Lactobacilli was successful in both species leading to lower Nugent score and pH, although rhesus macaques appeared better able to sustain Lactobacillus spp over time. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection

    Science.gov (United States)

    Stewart, Laurel M.; Koenig, Michelle; Semler, Matthew; Breitbach, Meghan E.; Zeng, Xiankun; Weiler, Andrea M.; Barry, Gabrielle L.; Thoong, Troy H.; Wiepz, Gregory J.; Dudley, Dawn M.; Simmons, Heather A.; Mejia, Andres; Morgan, Terry K.; Salamat, M. Shahriar; Kohn, Sarah; Antony, Kathleen M.; Mohns, Mariel S.; Hayes, Jennifer M.; Schultz-Darken, Nancy; Schotzko, Michele L.; Peterson, Eric; Capuano, Saverio; Osorio, Jorge E.; O’Connor, Shelby L.; O’Connor, David H.; Golos, Thaddeus G.

    2018-01-01

    Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout fetal tissues and maternal immune system tissues at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal uterus, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in a rhesus macaque. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital ZIKV infection previously. While this case of ZIKV infection during pregnancy was complicated by bacterial infection with PPROM, the role of ZIKV on this outcome cannot be precisely defined, and further nonhuman primate studies will determine if increased risk for PPROM or other adverse pregnancy outcomes are associated with congenital ZIKV infection. PMID:29381706

  15. Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques.

    Science.gov (United States)

    Magnani, Diogo M; Rogers, Thomas F; Maness, Nicholas J; Grubaugh, Nathan D; Beutler, Nathan; Bailey, Varian K; Gonzalez-Nieto, Lucas; Gutman, Martin J; Pedreño-Lopez, Núria; Kwal, Jaclyn M; Ricciardi, Michael J; Myers, Tereance A; Julander, Justin G; Bohm, Rudolf P; Gilbert, Margaret H; Schiro, Faith; Aye, Pyone P; Blair, Robert V; Martins, Mauricio A; Falkenstein, Kathrine P; Kaur, Amitinder; Curry, Christine L; Kallas, Esper G; Desrosiers, Ronald C; Goldschmidt-Clermont, Pascal J; Whitehead, Stephen S; Andersen, Kristian G; Bonaldo, Myrna C; Lackner, Andrew A; Panganiban, Antonito T; Burton, Dennis R; Watkins, David I

    2018-04-24

    Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission.

  16. Quantitative Proteomic Analysis of Hepatic Tissue of T2DM Rhesus Macaque

    Directory of Open Access Journals (Sweden)

    Tingfu Du

    2017-01-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a metabolic disorder that severely affects human health, but the pathogenesis of the disease remains unknown. The high-fat/high-sucrose diets combined with streptozotocin- (STZ- induced nonhuman primate animal model of diabetes are a valuable research source of T2DM. Here, we present a study of a STZ rhesus macaque model of T2DM that utilizes quantitative iTRAQ-based proteomic method. We compared the protein profiles in the liver of STZ-treated macaques as well as age-matched healthy controls. We identified 171 proteins differentially expressed in the STZ-treated groups, about 70 of which were documented as diabetes-related gene in previous studies. Pathway analyses indicated that the biological functions of differentially expressed proteins were related to glycolysis/gluconeogenesis, fatty acid metabolism, complements, and coagulation cascades. Expression change in tryptophan metabolism pathway was also found in this study which may be associations with diabetes. This study is the first to explore genome-wide protein expression in hepatic tissue of diabetes macaque model using HPLC-Q-TOF/MS technology. In addition to providing potential T2DM biomarkers, this quantitative proteomic study may also shed insights regarding the molecular pathogenesis of T2DM.

  17. Individual and social learning processes involved in the acquisition and generalization of tool use in macaques

    Science.gov (United States)

    Macellini, S.; Maranesi, M.; Bonini, L.; Simone, L.; Rozzi, S.; Ferrari, P. F.; Fogassi, L.

    2012-01-01

    Macaques can efficiently use several tools, but their capacity to discriminate the relevant physical features of a tool and the social factors contributing to their acquisition are still poorly explored. In a series of studies, we investigated macaques' ability to generalize the use of a stick as a tool to new objects having different physical features (study 1), or to new contexts, requiring them to adapt the previously learned motor strategy (study 2). We then assessed whether the observation of a skilled model might facilitate tool-use learning by naive observer monkeys (study 3). Results of study 1 and study 2 showed that monkeys trained to use a tool generalize this ability to tools of different shape and length, and learn to adapt their motor strategy to a new task. Study 3 demonstrated that observing a skilled model increases the observers' manipulations of a stick, thus facilitating the individual discovery of the relevant properties of this object as a tool. These findings support the view that in macaques, the motor system can be modified through tool use and that it has a limited capacity to adjust the learnt motor skills to a new context. Social factors, although important to facilitate the interaction with tools, are not crucial for tool-use learning. PMID:22106424

  18. Hierarchical ordering with partial pairwise hierarchical relationships on the macaque brain data sets.

    Directory of Open Access Journals (Sweden)

    Woosang Lim

    Full Text Available Hierarchical organizations of information processing in the brain networks have been known to exist and widely studied. To find proper hierarchical structures in the macaque brain, the traditional methods need the entire pairwise hierarchical relationships between cortical areas. In this paper, we present a new method that discovers hierarchical structures of macaque brain networks by using partial information of pairwise hierarchical relationships. Our method uses a graph-based manifold learning to exploit inherent relationship, and computes pseudo distances of hierarchical levels for every pair of cortical areas. Then, we compute hierarchy levels of all cortical areas by minimizing the sum of squared hierarchical distance errors with the hierarchical information of few cortical areas. We evaluate our method on the macaque brain data sets whose true hierarchical levels are known as the FV91 model. The experimental results show that hierarchy levels computed by our method are similar to the FV91 model, and its errors are much smaller than the errors of hierarchical clustering approaches.

  19. Topical tenofovir protects against vaginal simian HIV infection in macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis.

    Science.gov (United States)

    Makarova, Natalia; Henning, Tara; Taylor, Andrew; Dinh, Chuong; Lipscomb, Jonathan; Aubert, Rachael; Hanson, Debra; Phillips, Christi; Papp, John; Mitchell, James; McNicholl, Janet; Garcia-Lerma, Gerardo J; Heneine, Walid; Kersh, Ellen; Dobard, Charles

    2017-03-27

    Chlamydia trachomatis and Trichomonas vaginalis, two prevalent sexually transmitted infections, are known to increase HIV risk in women and could potentially diminish preexposure prophylaxis efficacy, particularly for topical interventions that rely on local protection. We investigated in macaques whether coinfection with Chlamydia trachomatis/Trichomonas vaginalis reduces protection by vaginal tenofovir (TFV) gel. Vaginal TFV gel dosing previously shown to provide 100 or 74% protection when applied either 30 min or 3 days before simian HIV(SHIV) challenge was assessed in pigtailed macaques coinfected with Chlamydia trachomatis/Trichomonas vaginalis and challenged twice weekly with SHIV162p3 for up to 10 weeks (two menstrual cycles). Three groups of six macaques received either placebo or 1% TFV gel 30 min or 3 days before each SHIV challenge. We additionally assessed TFV and TFV diphosphate concentrations in plasma and vaginal tissues in Chlamydia trachomatis/Trichomonas vaginalis coinfected (n = 4) and uninfected (n = 4) macaques. Chlamydia trachomatis/Trichomonas vaginalis coinfections were maintained during the SHIV challenge period. All macaques that received placebo gel were SHIV infected after a median of seven challenges (one menstrual cycle). In contrast, no infections were observed in macaques treated with TFV gel 30 min before SHIV challenge (P vaginal lymphocytes were significantly higher in Chlamydia trachomatis/Trichomonas vaginalis coinfected compared with Chlamydia trachomatis/Trichomonas vaginalis uninfected macaques. Our findings in this model suggest that Chlamydia trachomatis/Trichomonas vaginalis coinfection may have little or no impact on the efficacy of highly effective topical TFV modalities and highlight a significant modulation of TFV pharmacokinetics.

  20. Vaccines, our shared responsibility.

    Science.gov (United States)

    Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar

    2015-05-05

    The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN, together with the co-organizing institution Panacea Biotec, welcomed over 240 delegates representing high-profile governmental and nongovernmental global health organizations from 36 countries. Over the three-day meeting, attendees exchanged information about their efforts to achieve their shared goal of preventing death and disability from known and emerging infectious diseases. Special praise was extended to all stakeholders involved in the success of polio eradication in South East Asia and highlighted challenges in vaccine supply for measles-rubella immunization over the coming decades. Innovative vaccines and vaccine delivery technologies indicated creative solutions for achieving global immunization goals. Discussions were focused on three major themes including regulatory challenges for developing countries that may be overcome with better communication; global collaborations and partnerships for leveraging investments and enable uninterrupted supply of affordable and suitable vaccines; and leading innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid-conjugated and EV71, and needle-free technologies that may speed up vaccine delivery. Moving further into the Decade of Vaccines, participants renewed their commitment to shared responsibility toward a world free of vaccine-preventable diseases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Vaccines: Shaping global health.

    Science.gov (United States)

    Pagliusi, Sonia; Ting, Ching-Chia; Lobos, Fernando

    2017-03-14

    The Developing Countries Vaccine Manufacturers' Network (DCVMN) gathered leaders in immunization programs, vaccine manufacturing, representatives of the Argentinean Health Authorities and Pan American Health Organization, among other global health stakeholders, for its 17th Annual General Meeting in Buenos Aires, to reflect on how vaccines are shaping global health. Polio eradication and elimination of measles and rubella from the Americas is a result of successful collaboration, made possible by timely supply of affordable vaccines. After decades of intense competition for high-value markets, collaboration with developing countries has become critical, and involvement of multiple manufacturers as well as public- and private-sector investments are essential, for developing new vaccines against emerging infectious diseases. The recent Zika virus outbreak and the accelerated Ebola vaccine development exemplify the need for international partnerships to combat infectious diseases. A new player, Coalition for Epidemic Preparedness Innovations (CEPI) has made its entrance in the global health community, aiming to stimulate research preparedness against emerging infections. Face-to-face panel discussions facilitated the dialogue around challenges, such as risks of viability to vaccine development and regulatory convergence, to improve access to sustainable vaccine supply. It was discussed that joint efforts to optimizing regulatory pathways in developing countries, reducing registration time by up to 50%, are required. Outbreaks of emerging infections and the global Polio eradication and containment challenges are reminders of the importance of vaccines' access, and of the importance of new public-private partnerships. Copyright © 2017.

  2. Tetanus, Diphtheria, Pertussis (Tdap) Vaccine

    Science.gov (United States)

    Adacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Boostrix® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

  3. Clinical development of Ebola vaccines

    Science.gov (United States)

    Sridhar, Saranya

    2015-01-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

  4. Visual cortex and auditory cortex activation in early binocularly blind macaques: A BOLD-fMRI study using auditory stimuli.

    Science.gov (United States)

    Wang, Rong; Wu, Lingjie; Tang, Zuohua; Sun, Xinghuai; Feng, Xiaoyuan; Tang, Weijun; Qian, Wen; Wang, Jie; Jin, Lixin; Zhong, Yufeng; Xiao, Zebin

    2017-04-15

    Cross-modal plasticity within the visual and auditory cortices of early binocularly blind macaques is not well studied. In this study, four healthy neonatal macaques were assigned to group A (control group) or group B (binocularly blind group). Sixteen months later, blood oxygenation level-dependent functional imaging (BOLD-fMRI) was conducted to examine the activation in the visual and auditory cortices of each macaque while being tested using pure tones as auditory stimuli. The changes in the BOLD response in the visual and auditory cortices of all macaques were compared with immunofluorescence staining findings. Compared with group A, greater BOLD activity was observed in the bilateral visual cortices of group B, and this effect was particularly obvious in the right visual cortex. In addition, more activated volumes were found in the bilateral auditory cortices of group B than of group A, especially in the right auditory cortex. These findings were consistent with the fact that there were more c-Fos-positive cells in the bilateral visual and auditory cortices of group B compared with group A (p visual cortices of binocularly blind macaques can be reorganized to process auditory stimuli after visual deprivation, and this effect is more obvious in the right than the left visual cortex. These results indicate the establishment of cross-modal plasticity within the visual and auditory cortices. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Variation in hair δ13C and δ15N values in long-tailed macaques (Macaca fascicularis) from Singapore

    Science.gov (United States)

    Schillaci, Michael A.; Castellini, J. Margaret; Stricker, Craig A.; Jones-Engel, Lisa; Lee, Benjamin P.Y.-H.

    2014-01-01

    Much of the primatology literature on stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) has focused on African and New World species, with comparatively little research published on Asian primates. Here we present hair δ13C and δ15N isotope values for a sample of 33 long-tailed macaques from Singapore. We evaluate the suggestion by a previous researcher that forest degradation and biodiversity loss in Singapore have led to a decline in macaque trophic level. The results of our analysis indicated significant spatial variability in δ13C but not δ15N. The range of variation in δ13C was consistent with a diet based on C3 resources, with one group exhibiting low values consistent with a closed canopy environment. Relative to other macaque species from Europe and Asia, the macaques from Singapore exhibited a low mean δ13C value but mid-range mean δ15N value. Previous research suggesting a decline in macaque trophic level is not supported by the results of our study.

  6. Multigenic DNA vaccine induces protective cross-reactive T cell responses against heterologous influenza virus in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Merika T Koday

    Full Text Available Recent avian and swine-origin influenza virus outbreaks illustrate the ongoing threat of influenza pandemics. We investigated immunogenicity and protective efficacy of a multi-antigen (MA universal influenza DNA vaccine consisting of HA, M2, and NP antigens in cynomolgus macaques. Following challenge with a heterologous pandemic H1N1 strain, vaccinated animals exhibited significantly lower viral loads and more rapid viral clearance when compared to unvaccinated controls. The MA DNA vaccine induced robust serum and mucosal antibody responses but these high antibody titers were not broadly neutralizing. In contrast, the vaccine induced broadly-reactive NP specific T cell responses that cross-reacted with the challenge virus and inversely correlated with lower viral loads and inflammation. These results demonstrate that a MA DNA vaccine that induces strong cross-reactive T cell responses can, independent of neutralizing antibody, mediate significant cross-protection in a nonhuman primate model and further supports development as an effective approach to induce broad protection against circulating and emerging influenza strains.

  7. A DNA vaccine against chikungunya virus is protective in mice and induces neutralizing antibodies in mice and nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Karthik Mallilankaraman

    2011-01-01

    Full Text Available Chikungunya virus (CHIKV is an emerging mosquito-borne alphavirus indigenous to tropical Africa and Asia. Acute illness is characterized by fever, arthralgias, conjunctivitis, rash, and sometimes arthritis. Relatively little is known about the antigenic targets for immunity, and no licensed vaccines or therapeutics are currently available for the pathogen. While the Aedes aegypti mosquito is its primary vector, recent evidence suggests that other carriers can transmit CHIKV thus raising concerns about its spread outside of natural endemic areas to new countries including the U.S. and Europe. Considering the potential for pandemic spread, understanding the development of immunity is paramount to the development of effective counter measures against CHIKV. In this study, we isolated a new CHIKV virus from an acutely infected human patient and developed a defined viral challenge stock in mice that allowed us to study viral pathogenesis and develop a viral neutralization assay. We then constructed a synthetic DNA vaccine delivered by in vivo electroporation (EP that expresses a component of the CHIKV envelope glycoprotein and used this model to evaluate its efficacy. Vaccination induced robust antigen-specific cellular and humoral immune responses, which individually were capable of providing protection against CHIKV challenge in mice. Furthermore, vaccine studies in rhesus macaques demonstrated induction of nAb responses, which mimicked those induced in convalescent human patient sera. These data suggest a protective role for nAb against CHIKV disease and support further study of envelope-based CHIKV DNA vaccines.

  8. The Human Hookworm Vaccine.

    Science.gov (United States)

    Hotez, Peter J; Diemert, David; Bacon, Kristina M; Beaumier, Coreen; Bethony, Jeffrey M; Bottazzi, Maria Elena; Brooker, Simon; Couto, Artur Roberto; Freire, Marcos da Silva; Homma, Akira; Lee, Bruce Y; Loukas, Alex; Loblack, Marva; Morel, Carlos Medicis; Oliveira, Rodrigo Correa; Russell, Philip K

    2013-04-18

    Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy. The recombinant proteins are formulated on Alhydrogel(®) and are being tested in combination with a synthetic Toll-like receptor 4 agonist. The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut. Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil. The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic. Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Pricing of new vaccines.

    Science.gov (United States)

    Lee, Bruce Y; McGlone, Sarah M

    2010-08-01

    New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical, and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following ten components: 1. Conduct a target population analysis; 2. Map potential competitors and alternatives; 3. Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; 4. Quantify the incremental value of the new vaccine's characteristics; 5. Determine vaccine positioning in the marketplace; 6. Estimate the vaccine price-demand curve; 7. Calculate vaccine costs (including those of manufacturing, distribution, and research and development); 8. Account for various legal, regulatory, third party payer, and competitor factors; 9. Consider the overall product portfolio; 10. Set pricing objectives; 11. Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area.

  10. Pricing of new vaccines

    Science.gov (United States)

    McGlone, Sarah M

    2010-01-01

    New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following eleven components: (1) Conduct a target population analysis; (2) Map potential competitors and alternatives; (3) Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; (4) Quantify the incremental value of the new vaccine's characteristics; (5) Determine vaccine positioning in the marketplace; (6) Estimate the vaccine price-demand curve; (7) Calculate vaccine costs (including those of manufacturing, distribution, and research and development); (8) Account for various legal, regulatory, third party payer and competitor factors; (9) Consider the overall product portfolio; (10) Set pricing objectives; (11) Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area. PMID:20861678

  11. Acceptance of vaccination

    NARCIS (Netherlands)

    Lehmann, B.; Eilers, R.; Donken, R.; Barug, D.; Swillens, J.; Vriend, C. de; Weerdenburg, S.; Pot, M.; Keulen, H. van; Paulussen, T.; Vermey, K.; Alberts, N.; Marra, E.; Melker, H.E. de; Mollema, L.

    2016-01-01

    Both in 2013 and 2015 the mean intention of parents to vaccinate their child was high. Only 21% of parents reported making an informed decision about childhood vaccinations included in the NIP. Mass media attention on the use of allegedly inferior needles, which was later refuted, appeared to have a

  12. Vaccines Stop Illness

    Science.gov (United States)

    ... the disease no longer exists. If we keep vaccinating now, parents in the future may be able to trust that diseases like polio and meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about ...

  13. Chimeric Pestivirus Experimental Vaccines.

    Science.gov (United States)

    Reimann, Ilona; Blome, Sandra; Beer, Martin

    2016-01-01

    Chimeric pestiviruses have shown great potential as marker vaccine candidates against pestiviral infections. Exemplarily, we describe here the construction and testing of the most promising classical swine fever vaccine candidate "CP7_E2alf" in detail. The description is focused on classical cloning technologies in combination with reverse genetics.

  14. Vaccination Perceptions of College Students: With and without Vaccination Waiver.

    Science.gov (United States)

    Jadhav, Emmanuel D; Winkler, Danielle L; Anderson, Billie S

    2018-01-01

    The resurgence of vaccine preventable diseases occurs more often among intentionally unvaccinated individuals, placing at direct risk young adults not caught up on vaccinations. The objectives of this study were to characterize the sociodemographic characteristics of young adults with and without vaccination waivers and identify their perceived benefits, barriers, and influencers of vaccination. Young adults ( n  = 964) from a Midwestern rural university responded to a survey (fall 2015-spring 2016) designed to identify their perception toward vaccination. Instrument consistency was measured using the Cronbach α-scores. The Chi-square test was used to test any sociodemographic differences and Mann-Whitney U -tests results for differences between exempt and non-exempt students. Analysis occurred in spring 2017. A little over one-third of young adults with a vaccination waiver were not up to date on their vaccinations, and think that vaccinations can cause autism. The biggest identifiable benefit was effective control against disease. The surveyed young adults ranked the out of pocket cost associated with vaccination as the most important barrier and safe and easy to use vaccines as the most important influencer of vaccination. Young adults who have had a vaccination waiver appear to not be up to date on their vaccinations. Vaccine administration programs, such as university campus clinics, would benefit from addressing perceptions unique to young adults with and without a vaccine waiver. This would subsequently better provide young adults a second shot for getting appropriately caught up on vaccinations.

  15. DNA fusion gene vaccines

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Bassi, Maria Rosaria; Thomsen, Allan Randrup

    2010-01-01

    DNA vaccines are versatile and safe, but limited immunogenicity has prevented their use in the clinical setting. Experimentally, immunogenicity may be enhanced by the use of new delivery technologies, by coadministration of cytokines and pathogen-associated molecular patterns, or by fusion...... of antigens into molecular domains that enhance antigen presentation. More specifically, the immunogenicity of DNA vaccines may benefit from increased protein synthesis, increased T-cell help and MHC class I presentation, and the addition of a range of specific cytokines and pathogen-associated molecular...... with viral-vectored vaccines, various synergistic components may need to be incorporated into DNA vaccines. From the perspective of the future clinical use of DNA vaccines, it has been suggested that antigen presentation should be improved and cytokine coadministration attempted. However, even...

  16. Financing children's vaccines.

    Science.gov (United States)

    Nelson, E Anthony S; Sack, David; Wolfson, Lara; Walker, Damian G; Seng, Lim Fong; Steele, Duncan

    2009-11-20

    A 2006 Commonwealth Association of Paediatric Gastroenterology and Nutrition workshop on financing children's vaccines highlighted the potential for vaccines to control diarrhoea and other diseases as well as spur economic development through better health. Clear communication of vaccination value to decision-makers is required, together with sustainable funding mechanisms. GAVI and partners have made great progress providing funding for vaccines for children in the poorest countries but other solutions may be required to achieve the same gains in middle- and high-income countries. World Health Organization has a wealth of freely available country-level data on immunisation that academics and advocates can use to communicate the economic and health benefits of vaccines to decision-makers.

  17. Next generation vaccines.

    Science.gov (United States)

    Riedmann, Eva M

    2011-07-01

    In February this year, about 100 delegates gathered for three days in Vienna (Austria) for the Next Generation Vaccines conference. The meeting held in the Vienna Hilton Hotel from 23rd-25th February 2011 had a strong focus on biotech and industry. The conference organizer Jacob Fleming managed to put together a versatile program ranging from the future generation of vaccines to manufacturing, vaccine distribution and delivery, to regulatory and public health issues. Carefully selected top industry experts presented first-hand experience and shared solutions for overcoming the latest challenges in the field of vaccinology. The program also included several case study presentations on novel vaccine candidates in different stages of development. An interactive pre-conference workshop as well as interactive panel discussions during the meeting allowed all delegates to gain new knowledge and become involved in lively discussions on timely, interesting and sometimes controversial topics related to vaccines.

  18. Development of antifertility vaccine using sperm specific proteins

    Directory of Open Access Journals (Sweden)

    A H Bandivdekar

    2014-01-01

    Full Text Available Sperm proteins are known to be associated with normal fertilization as auto- or iso-antibodies to these proteins may cause infertility. Therefore, sperm proteins have been considered to be the potential candidate for the development of antifertility vaccine. Some of the sperm proteins proved to be promising antigens for contraceptive vaccine includes lactate dehydrogenase (LDH-C4, protein hyaluronidase (PH-20, and Eppin. Immunization with LDH-C4 reduced fertility in female baboons but not in female cynomolgus macaques. Active immunization with PH-20 resulted in 100 per cent inhibition of fertility in male guinea pigs but it induced autoimmune orchitis. Immunization with Eppin elicited high antibody titres in 78 per cent of immunized monkeys and induced infertility but the immunopathological effect of immunization was not examined. Human sperm antigen (80kDa HSA is a sperm specific, highly immunogenic and conserved sperm protein. Active immunization with 80kDa HSA induced immunological infertility in male and female rats. Partial N-terminal amino acid sequence of 80kDa HSA (Peptide NT and its peptides (Peptides 1, 2, 3 and 4 obtained by enzymatic digestion did not show homology with any of the known proteins in gene bank. Peptides NT, 1, 2 and 4 were found to mimic immunobiological activity of native protein. Passive administration of antibodies to peptides NT, 1, 2 and 4 induced infertility in male and female rats and peptide 1 was found to be most effective in suppressing fertility. Active immunization with keyhole limpet haemocynin (KLH conjugated synthetic peptide 1 impaired fertility in all the male rabbits and six of the seven male marmosets. The fertility was restored following decline in antibody titre. All these findings on 80kDA HAS suggest that the synthetic Peptide-1 of 80kDa HSA is the promising candidate for development of male contraceptive vaccine.

  19. HIV vaccines: new frontiers in vaccine development.

    Science.gov (United States)

    Duerr, Ann; Wasserheit, Judith N; Corey, Lawrence

    2006-08-15

    A human immunodeficiency virus (HIV) vaccine is the most promising and feasible strategy to prevent the events during acute infection that simultaneously set the course of the epidemic in the community and the course of the disease for the individual. Because safety concerns limit the use of live, attenuated HIV and inactivated HIV, a variety of alternate approaches is being investigated. Traditional antibody-mediated approaches using recombinant HIV envelope proteins have shown no efficacy in 2 phase III trials. Current HIV vaccine trials are focusing primarily on cytotoxic T lymphocyte-mediated products that use viral vectors, either alone or as boosts to DNA plasmids that contain viral genes. The most immunogenic of these products appear to be the recombinant adenovirus vector vaccines, 2 of which are now in advanced clinical development.

  20. Prevention of pneumonic plague in mice, rats, guinea pigs and non-human primates with clinical grade rV10, rV10-2 or F1-V vaccines

    Science.gov (United States)

    Quenee, Lauriane E.; Ciletti, Nancy A.; Elli, Derek; Hermanas, Timothy M.; Schneewind, Olaf

    2012-01-01

    Yersinia pestis causes plague, a disease with high mortality in humans that can be transmitted by fleabite or aerosol. A US Food and Drug Administration (FDA)-licensed plague vaccine is currently not available. Vaccine developers have focused on two subunits of Y. pestis: LcrV, a protein at the tip of type III secretion needles, and F1, the fraction 1 pilus antigen. F1-V, a hybrid generated via translational fusion of both antigens, is being developed for licensure as a plague vaccine. The rV10 vaccine is a non-toxigenic variant of LcrV lacking residues 271–300. Here we developed Current Good Manufacturing Practice (cGMP) protocols for rV10. Comparison of clinical grade rV10 with F1-V did not reveal significant differences in plague protection in mice, guinea pigs or cynomolgus macaques. We also developed cGMP protocols for rV10-2, a variant of rV10 with an altered affinity tag. Immunization with rV10-2 adsorbed to aluminum hydroxide elicited antibodies against LcrV and conferred pneumonic plague protection in mice, rats, guinea pigs, cynomolgus macaques and African Green monkeys. The data support further development of rV10-2 for FDA Investigational New Drug (IND) authorization review and clinical testing. PMID:21763383

  1. Combining biomedical preventions for HIV: Vaccines with pre-exposure prophylaxis, microbicides or other HIV preventions.

    Science.gov (United States)

    McNicholl, Janet M

    2016-12-01

    Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention.

  2. Laser vaccine adjuvants

    Science.gov (United States)

    Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

    2014-01-01

    Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797

  3. Vaccines for canine leishmaniasis

    Directory of Open Access Journals (Sweden)

    Clarisa B. Palatnik-De-Sousa

    2012-04-01

    Full Text Available Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global-warming, co-infection with immunosuppressive diseases and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL in the Americas, the Middle East, Central Asia, China and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine visceral leishmaniasis. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans

  4. Vaccination in food allergic patients

    African Journals Online (AJOL)

    Most people do not react to vaccination and the incidence of vaccine anaphylaxis is estimated to be <1/million for all vaccines.[1] Most anaphylactic reactions occur in non-food allergic children. It is strongly recommended that anyone admin- istering vaccines has resuscitation equipment available to manage potential ...

  5. Parental knowledge of paediatric vaccination

    Directory of Open Access Journals (Sweden)

    Borràs Eva

    2009-05-01

    Full Text Available Abstract Background Although routine vaccination is a major tool in the primary prevention of some infectious diseases, there is some reluctance in a proportion of the population. Negative parental perceptions of vaccination are an important barrier to paediatric vaccination. The aim of this study was to investigate parental knowledge of paediatric vaccines and vaccination in Catalonia. Methods A retrospective, cross-sectional study was carried out in children aged Results An association was observed between greater vaccination coverage of the 4:4:4:3:1 schedule (defined as: 4 DTPa/w doses, 4 Hib doses, 4 OPV doses, 3 MenC doses and 1 MMR dose and maternal age >30 years (OR: 2.30; 95% CI: 1.20–4.43 and with a knowledge of vaccination score greater than the mean (OR: 0.45; 95% CI: 0.28–0.72. The score increased with maternal educational level and in parents of vaccinated children. A total of 20.47% of parents stated that vaccines could have undesirable consequences for their children. Of these, 23.26% had no specific information and 17.83% stated that vaccines can cause adverse reactions and the same percentage stated that vaccines cause allergies and asthma. Conclusion Higher vaccination coverage is associated with older maternal age and greater knowledge of vaccination. Vaccination coverage could be raised by improving information on vaccines and vaccination.

  6. Host immune responses to a viral immune modulating protein: immunogenicity of viral interleukin-10 in rhesus cytomegalovirus-infected rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Meghan K Eberhardt

    Full Text Available Considerable evidence has accumulated that multiple viruses, bacteria, and protozoa manipulate interleukin-10 (IL-10-mediated signaling through the IL-10 receptor (IL-10R in ways that could enable establishment of a persistent microbial infection. This suggests that inhibition of pathogen targeting of IL-10/IL-10R signaling could prevent microbial persistence. Human cytomegalovirus (HCMV and rhesus cytomegalovirus (RhCMV express a viral interleukin-10 (cmvIL-10 and rhcmvIL-10, respectively with comparable immune modulating properties in vitro to that of their host's cellular IL-10 (cIL-10. A prior study noted that rhcmvIL-10 alters innate and adaptive immunity to RhCMV in vivo, consistent with a central role for rhcmvIL-10 during acute virus-host interactions. Since cmvIL-10 and rhcmvIL-10 are extremely divergent from the cIL-10 of their respective hosts, vaccine-mediated neutralization of their function could inhibit establishment of viral persistence without inhibition of cIL-10.As a prelude to evaluating cmvIL-10-based vaccines in humans, the rhesus macaque model of HCMV was used to interrogate peripheral and mucosal immune responses to rhcmvIL-10 in RhCMV-infected animals. ELISA were used to detect rhcmvIL-10-binding antibodies in plasma and saliva, and an IL-12-based bioassay was used to quantify plasma antibodies that neutralized rhcmvIL-10 function. rhcmvIL-10 is highly immunogenic during RhCMV infection, stimulating high avidity rhcmvIL-10-binding antibodies in the plasma of all infected animals. Most infected animals also exhibited plasma antibodies that partially neutralized rhcmvIL-10 function but did not cross-neutralize the function of rhesus cIL-10. Notably, minimally detectable rhcmvIL-10-binding antibodies were detected in saliva.This study demonstrates that rhcmvIL-10, as a surrogate for cmvIL-10, is a viable vaccine candidate because (1 it is highly immunogenic during natural RhCMV infection, and (2 neutralizing antibodies to

  7. Bioinformatics analysis of Brucella vaccines and vaccine targets using VIOLIN.

    Science.gov (United States)

    He, Yongqun; Xiang, Zuoshuang

    2010-09-27

    Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis, one of the commonest zoonotic diseases found worldwide in humans and a variety of animal species. While several animal vaccines are available, there is no effective and safe vaccine for prevention of brucellosis in humans. VIOLIN (http://www.violinet.org) is a web-based vaccine database and analysis system that curates, stores, and analyzes published data of commercialized vaccines, and vaccines in clinical trials or in research. VIOLIN contains information for 454 vaccines or vaccine candidates for 73 pathogens. VIOLIN also contains many bioinformatics tools for vaccine data analysis, data integration, and vaccine target prediction. To demonstrate the applicability of VIOLIN for vaccine research, VIOLIN was used for bioinformatics analysis of existing Brucella vaccines and prediction of new Brucella vaccine targets. VIOLIN contains many literature mining programs (e.g., Vaxmesh) that provide in-depth analysis of Brucella vaccine literature. As a result of manual literature curation, VIOLIN contains information for 38 Brucella vaccines or vaccine candidates, 14 protective Brucella antigens, and 68 host response studies to Brucella vaccines from 97 peer-reviewed articles. These Brucella vaccines are classified in the Vaccine Ontology (VO) system and used for different ontological applications. The web-based VIOLIN vaccine target prediction program Vaxign was used to predict new Brucella vaccine targets. Vaxign identified 14 outer membrane proteins that are conserved in six virulent strains from B. abortus, B. melitensis, and B. suis that are pathogenic in humans. Of the 14 membrane proteins, two proteins (Omp2b and Omp31-1) are not present in B. ovis, a Brucella species that is not pathogenic in humans. Brucella vaccine data stored in VIOLIN were compared and analyzed using the VIOLIN query system. Bioinformatics curation and ontological representation of Brucella vaccines

  8. [Current events in vaccination].

    Science.gov (United States)

    Aubert, M; Aumaître, H; Beytout, J; Bloch, K; Bouhour, D; Callamand, P; Chave, C; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; De Pontual, L; Dodet, B; Dommergues, M-A; Dufour, V; Gagneur, A; Gaillat, J; Gaudelus, J; Gavazzi, G; Gillet, Y; Gras-le-Guen, C; Haas, H; Hanslik, T; Hau-Rainsard, I; Larnaudie, S; Launay, O; Lorrot, M; Loulergue, P; Malvy, D; Marchand, S; Picherot, G; Pinquier, D; Pulcini, C; Rabaud, C; Regnier, F; Reinert, P; Sana, C; Savagner, C; Soubeyrand, B; Stephan, J-L; Strady, C

    2011-11-01

    The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine

  9. Technical Transformation of Biodefense Vaccines

    Science.gov (United States)

    Lu, Shan; Wang, Shixia

    2013-01-01

    Biodefense vaccines are developed against a diverse group of pathogens. Vaccines were developed for some of these pathogens a long time ago but they are facing new challenges to move beyond the old manufacturing technologies. New vaccines to be developed against other pathogens have to determine whether to follow traditional vaccination strategies or to seek new approaches. Advances in basic immunology and recombinant DNA technology have fundamentally transformed the process of formulating a vaccine concept, optimizing protective antigens, and selecting the most effective vaccine delivery approach for candidate biodefense vaccines. PMID:19837293

  10. Food resources, distribution and seasonal variations in ranging in lion-tailed macaques, Macaca silenus in the Western Ghats, India.

    Science.gov (United States)

    Erinjery, Joseph J; Kavana, T S; Singh, Mewa

    2015-01-01

    The distribution and availability of food was examined to see how it influenced ranging patterns and sleeping site selection in a group of lion-tailed macaques. The home range and core area were 130.48 ha (95% kernel) and 26.68 ha (50% kernel) respectively. The lion-tailed macaques had a longer day range, had a greater number of sleeping sites and used more core areas in the summer as compared to the monsoon and the post-monsoon seasons. The ranging patterns and sleeping site use were influenced by the major food resources used in a particular season. The ranging was mainly influenced by Artocarpus heterophyllus in monsoon, Cullenia exarillata and Toona ciliata in post- monsoon, and Artocarpus heterophyllus and Ficus amplissima in summer. The distribution of these four plant species is, therefore, critical to ranging, and thus to conservation of the lion-tailed macaque.

  11. Progress towards a Leishmania vaccine.

    Science.gov (United States)

    Tabbara, Khaled S

    2006-07-01

    Leishmaniasis is a vector-born protozoan disease. Approximately 12 million individuals are affected worldwide with an estimated annual incidence of 1.5-2 million. Two clinical manifestations are recognized, cutaneous, and visceral, both of which are common in the Middle East. In both forms, infection is chronic, with potential deformities, persistence following cure, and lifelong risk of reactivation. Attempts to develop an effective human Leishmania vaccine have not yet succeeded. Leishmanization, a crude form of live vaccination historically originated in this part of the world. Experimental vaccination has been extensively studied in model animals in the past 2 decades. In this review, major human killed vaccine trials are surveyed, and modern trends in Leishmania vaccine development, including subunit vaccines, naked DNA vaccines, and transmission blocking vaccines are explored. Recent findings of a link between persistence of live parasites, and maintenance of long-term immunity suggest live vaccination with attenuated strains, as a future vaccination strategy.

  12. [Development of current smallpox vaccines].

    Science.gov (United States)

    Maksiutov, R A; Gavrilova, E V; Shchelkunov, S N

    2011-01-01

    The review gives data on the history of smallpox vaccination and shows the high topicality of designing the current safe vaccines against orthopoxviruses. Four generations of live smallpox, protein subunit, and DNA vaccines are considered. Analysis of the data published leads to the conclusion that it is promising to use the up-to-date generations of safe smallpox subunit or DNA vaccines for mass primary immunization with possible further revaccination with classical live vaccine.

  13. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  14. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, M; Met, Ö; Svane, I M

    2012-01-01

    Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... to transiently affect in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

  15. ADE and dengue vaccination.

    Science.gov (United States)

    Martínez-Vega, Ruth Aralí; Carrasquila, Gabriel; Luna, Expedito; Ramos-Castañeda, José

    2017-07-13

    The vaccine against Dengue virus (DENV), Dengvaxia® (CYD), produced by Sanofi-Pasteur, has been registered by several national regulatory agencies; nevertheless, the performance and security of this vaccine have been challenged in a series of recent papers. In this work, we intend to contribute to the debate by analyzing the concept of an enhancing vaccine, presenting objections to the epidemiological model base of the concept and, likewise, presenting data that contradict that concept. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The rhesus macaque is three times as diverse but more closely equivalent in damaging coding variation as compared to the human

    Directory of Open Access Journals (Sweden)

    Yuan Qiaoping

    2012-06-01

    Full Text Available Abstract Background As a model organism in biomedicine, the rhesus macaque (Macaca mulatta is the most widely used nonhuman primate. Although a draft genome sequence was completed in 2007, there has been no systematic genome-wide comparison of genetic variation of this species to humans. Comparative analysis of functional and nonfunctional diversity in this highly abundant and adaptable non-human primate could inform its use as a model for human biology, and could reveal how variation in population history and size alters patterns and levels of sequence variation in primates. Results We sequenced the mRNA transcriptome and H3K4me3-marked DNA regions in hippocampus from 14 humans and 14 rhesus macaques. Using equivalent methodology and sampling spaces, we identified 462,802 macaque SNPs, most of which were novel and disproportionately located in the functionally important genomic regions we had targeted in the sequencing. At least one SNP was identified in each of 16,797 annotated macaque genes. Accuracy of macaque SNP identification was conservatively estimated to be >90%. Comparative analyses using SNPs equivalently identified in the two species revealed that rhesus macaque has approximately three times higher SNP density and average nucleotide diversity as compared to the human. Based on this level of diversity, the effective population size of the rhesus macaque is approximately 80,000 which contrasts with an effective population size of less than 10,000 for humans. Across five categories of genomic regions, intergenic regions had the highest SNP density and average nucleotide diversity and CDS (coding sequences the lowest, in both humans and macaques. Although there are more coding SNPs (cSNPs per individual in macaques than in humans, the ratio of dN/dS is significantly lower in the macaque. Furthermore, the number of damaging nonsynonymous cSNPs (have damaging effects on protein functions from PolyPhen-2 prediction in the macaque is more

  17. MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques.

    Science.gov (United States)

    Brammer, David W; Gillespie, Patrick J; Tian, Mei; Young, Daniel; Raveendran, Muthuswamy; Williams, Lawrence E; Gagea, Mihai; Benavides, Fernando J; Perez, Carlos J; Broaddus, Russell R; Bernacky, Bruce J; Barnhart, Kirstin F; Alauddin, Mian M; Bhutani, Manoop S; Gibbs, Richard A; Sidman, Richard L; Pasqualini, Renata; Arap, Wadih; Rogers, Jeffrey; Abee, Christian R; Gelovani, Juri G

    2018-03-13

    Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques ( Macaca mulatta ) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) and [ 18 F]fluoroacetate ([ 18 F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [ 18 F]fluorothymidine ([ 18 F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1 -rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans. Copyright © 2018 the Author(s). Published by PNAS.

  18. Tracing the phylogeographic history of Southeast Asian long-tailed macaques through mitogenomes of museum specimens.

    Science.gov (United States)

    Yao, Lu; Li, Hongjie; Martin, Robert D; Moreau, Corrie S; Malhi, Ripan S

    2017-11-01

    The biogeographical history of Southeast Asia is complicated due to the continuous emergences and disappearances of land bridges throughout the Pleistocene. Here, we use long-tailed macaques (Macaca fascicularis), which are widely distributed throughout the mainland and islands of Southeast Asia, asa model for better understanding the biogeographical patterns of diversification in this geographically complex region. A reliable intraspecific phylogeny including individuals from localities on oceanic islands, continental islands, and the mainland is needed to trace relatedness along with the pattern and timing of colonization in this region. We used high-throughput sequencing techniques to sequence mitochondrial genomes (mitogenomes) from 95 Southeast Asian M. fascicularis specimens housed at natural history museums around the world. To achieve a comprehensive picture, we more than tripled the mitogenome sample size for M. fascicularis from previous studies, and for the first time included documented samples from the Philippines and several small Indonesian islands. Confirming the result from a previous, recent intraspecific phylogeny for M. fascicularis, the newly reconstructed phylogeny of 135 specimens divides the samples into two major clades: Clade A includes haplotypes from the mainland and some from northern Sumatra, while Clade B includes all insular haplotypes along with lineages from southern Sumatra. This study resolves a previous disparity by revealing a disjunction in the origin of Sumatran macaques, with separate lineages originating within the two major clades, suggesting that at least two major migrations to Sumatra occurred. However, our dated phylogeny reveals that the two major clades split ∼1.88Ma, which is earlier than in previously published phylogenies. Our new data reveal that most Philippine macaque lineages diverged from the Borneo stock within the last ∼0.06-0.43Ma. Finally, our study provides insight into successful sequencing of DNA

  19. Comparison of feeding behavior between two different-sized groups of Japanese macaques (Macaca fuscata yakui).

    Science.gov (United States)

    Kurihara, Yosuke; Hanya, Goro

    2015-05-13

    Group-living animals face intragroup scramble and intergroup contest competitions. Many studies have shown that larger groups bear the costs of intragroup scramble competition, which negatively affects the reproductive success of females. Unlike most primate species, Japanese macaques in the Yakushima coastal forest show increased reproductive success with group size. However, it remains unclear how group size affects the behavior of macaques. The present study examined the effects of group size on the feeding behavior of Japanese macaques in the Yakushima coastal forest. We investigated 9-13 adult females from two different-sized groups via focal animal sampling during October 2012-August 2013. We compared the feeding behavior, including patch use, between the two groups. The larger group had a larger home range and spent more time feeding, especially on mature leaves. This suggests that intragroup feeding competition should be more intense in the larger group than in the smaller group. The feeding of mature leaves might enable the larger group to increase the number of co-feeding individuals. Contrary to the predictions that the larger group travels longer distances and spends more time moving, the smaller group traveled longer distances, and spent more time moving, although the number of visited patches did not differ between the two groups. The immediate consequences of the loss of inter-group encounters could accumulate as daily travel costs, considering that group size is associated with inter-group dominance and that intergroup aggressive encounters occur frequently in the Yakushima coastal forest. This suggests that the smaller group has increased travel costs as a result of intergroup contest competition, which leads to decline in reproductive success. Am. J. Primatol. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  20. Cortico-cortical connections of areas 44 and 45B in the macaque monkey.

    Science.gov (United States)

    Frey, Stephen; Mackey, Scott; Petrides, Michael

    2014-04-01

    In the human brain, areas 44 and 45 constitute Broca's region, the ventrolateral frontal region critical for language production. The homologues of these areas in the macaque monkey brain have been established by direct cytoarchitectonic comparison with the human brain. The cortical areas that project monosynaptically to areas 44 and 45B in the macaque monkey brain require clarification. Fluorescent retrograde tracers were placed in cytoarchitectonic areas 44 and 45B of the macaque monkey, as well as in the anterior part of the inferior parietal lobule and the superior temporal gyrus. The results demonstrate that ipsilateral afferent connections of area 44 arise from local frontal areas, including rostral premotor cortical area 6, from secondary somatosensory cortex, the caudal insula, and the cingulate motor region. Area 44 is strongly linked with the anterior inferior parietal lobule (particularly area PFG and the adjacent anterior intraparietal sulcus). Input from the temporal lobe is limited to the fundus of the superior temporal sulcus extending caudal to the central sulcus. There is also input from the sulcal part of area Tpt in the upper bank of the superior temporal sulcus. Area 45B shares some of the connections of area 44, but can be distinguished from area 44 by input from the caudal inferior parietal lobule (area PG) and significant input from the part of the superior temporal sulcus that extends anterior to the central sulcus. Area 45B also receives input from visual association cortex that is not observed in area 44. The results have provided a clarification of the relative connections of areas 44 and 45B of the ventrolateral frontal region which, in the human brain, subserves certain aspects of language processing. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Social play among juvenile wild Japanese macaques (Macaca fuscata) strengthens their social bonds.

    Science.gov (United States)

    Shimada, Masaki; Sueur, Cédric

    2018-01-01

    Social play and grooming are typical affiliative interactions for many primate species, and are thought to have similar biological functions. However, grooming increases with age, whereas social play decreases. We proposed the hypothesis that both social grooming and social play in juveniles strengthen their social bonds in daily activities. We carried out field research on the social relationships among juvenile wild Japanese macaques in a troop in Kinkazan, Miyagi Prefecture, Japan, from fall 2007 to spring 2008 to investigate this hypothesis. We evaluated three relationships among juveniles, play indices (PI), grooming indices (GI), and 3-m-proximity indices (3mI) of each dyad (i.e., interacting pair), and compared these social networks based on the matrices of the indices. The play and grooming networks were correlated with the association network throughout the two research periods. The multiple network level measurements of the play network, but not the grooming network, resembled those of the association network. Using a causal step approach, we showed that social play and grooming interactions in fall seem to predict associations in the following spring, controlling for the PI and GI matrix in spring, respectively. Social play and grooming for each juvenile were negatively correlated. The results partially support our predictions; therefore, the hypothesis that the biological function of social play among immature Japanese macaques is to strengthen their social bonds in the near future and develop their social life appears to be correct. For juvenile macaques, social play, rather than grooming, functions as an important social mechanism to strengthen affiliative relationships. © 2017 Wiley Periodicals, Inc.

  2. Alpha male replacements and delayed dispersal in crested macaques (Macaca nigra).

    Science.gov (United States)

    Marty, Pascal R; Hodges, Keith; Agil, Muhammad; Engelhardt, Antje

    2017-07-01

    In species with a high male reproductive skew, competition between males for the top dominant position is high and escalated fights are common between competitors. As a consequence, challenges incur potentially high costs. Selection should favor males who time an alpha male challenge to maximize chances of a successful outcome minimizing costs. Despite the importance of alpha male replacements for individual males, we know little about the timing of challenges and the condition of the challenger. We investigated the timing and process of alpha male replacements in a species living in multi-male groups with high male reproductive skew, the crested macaque. We studied four wild groups over 6 years in the Tangkoko Reserve, North Sulawesi, Indonesia, during which 16 alpha male replacements occurred. Although unusual for cercopithecines, male crested macaques delayed their natal dispersal until they attained maximum body mass and therefore fighting ability whereupon they emigrated and challenged the alpha male in another group. Accordingly, all observed alpha male replacements were from outside males. Ours is the first report of such a pattern in a primate species living in multi-male groups. Although the majority of alpha male replacements occurred through direct male-male challenges, many also took place opportunistically (i.e., after the alpha male had already been injured or had left the group). Furthermore, alpha male tenures were very short (averaging ca. 12 months). We hypothesize that this unusual pattern of alpha male replacements in crested macaques is related to the species-specific combination of high male reproductive skew with a large number of males per group. Am. J. Primatol. 79:e22448, 2017. © 2015 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc. © 2015 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc.

  3. Naltrexone treatment reverses astrocyte atrophy and immune dysfunction in self-harming macaques.

    Science.gov (United States)

    Lee, Kim M; Chiu, Kevin B; Didier, Peter J; Baker, Kate C; MacLean, Andrew G

    2015-11-01

    The role of glia in the development and treatment of behavioral abnormalities is understudied. Recent reports have observed glial activation in several disorders, including depression, autism spectrum disorders and self-injurious behaviors (SIB). In the current study, we examined SIB in the physiologically and anatomically relevant nonhuman primate (NHP) model. At the Tulane National Primate Research Center (TNPRC), approximately 5% of singly housed macaques develop symptoms of SIB. We have previously demonstrated that naltrexone hydrochloride can be effective in reducing SIB. We have also demonstrated that the astrocytes of animals with SIB are distinctly atrophic and display heightened innate immune activation compared with control animals. We have added a third group of animals (five macaques identified with SIB and treated with oral naltrexone at a dose of 3.2mg/kg) to the previous cohort (six macaques with a history of SIB but not treated, and nine animals with no history of SIB) for this study. Gray and white matter astrocytes from frontal cortical tissue were examined following necropsy. Innate immune activation of astrocytes, which was increased in SIB animals, was markedly decreased in animals receiving naltrexone, as was atrophy of both grey and white matter astrocytes. This was concomitant with improved behavioral correlates. Preventing astrocyte activation in select areas of the brain to reduce injurious behavior is an innovative concept with implications for mental health studies. Differences in multiple areas of primate brain would help determine how self-injurious behavior develops. These studies suggest a stronger role for astrocytes in the cellular events associated with self-injurious behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Social relevance drives viewing behavior independent of low-level salience in rhesus macaques

    Directory of Open Access Journals (Sweden)

    James Andrew Solyst

    2014-11-01

    Full Text Available Quantifying attention to social stimuli during the viewing of complex social scenes with eye tracking has proven to be a sensitive method in the diagnosis of autism spectrum disorders years before average clinical diagnosis. Rhesus macaques provide an ideal model for understanding the mechanisms underlying social viewing behavior, but to date no comparable behavioral task has been developed for use in monkeys. Using a novel scene-viewing task, we monitored the gaze of three rhesus macaques while they freely viewed well-controlled composed social scenes and analyzed the time spent viewing objects and monkeys. In each of six behavioral sessions, monkeys viewed a set of 90 images (540 unique scenes with each image presented twice. In two-thirds of the repeated scenes, either a monkey or an object was replaced with a novel item (manipulated scenes. When viewing a repeated scene, monkeys made longer fixations and shorter saccades, shifting from a rapid orienting to global scene contents to a more local analysis of fewer items. In addition to this repetition effect, in manipulated scenes, monkeys demonstrated robust memory by spending more time viewing the replaced items. By analyzing attention to specific scene content, we found that monkeys strongly preferred to view conspecifics and that this was not related to their salience in terms of low-level image features. A model-free analysis of viewing statistics found that monkeys that were viewed earlier and longer had direct gaze and redder sex skin around their face and rump, two important visual social cues. These data provide a quantification of viewing strategy, memory and social preferences in rhesus macaques viewing complex social scenes, and they provide an important baseline with which to compare to the effects of therapeutics aimed at enhancing social cognition.

  5. Serotonin Decreases the Gain of Visual Responses in Awake Macaque V1.

    Science.gov (United States)

    Seillier, Lenka; Lorenz, Corinna; Kawaguchi, Katsuhisa; Ott, Torben; Nieder, Andreas; Pourriahi, Paria; Nienborg, Hendrikje

    2017-11-22

    Serotonin, an important neuromodulator in the brain, is implicated in affective and cognitive functions. However, its role even for basic cortical processes is controversial. For example, in the mammalian primary visual cortex (V1), heterogenous serotonergic modulation has been observed in anesthetized animals. Here, we combined extracellular single-unit recordings with iontophoresis in awake animals. We examined the role of serotonin on well-defined tuning properties (orientation, spatial frequency, contrast, and size) in V1 of two male macaque monkeys. We find that in the awake macaque the modulatory effect of serotonin is surprisingly uniform: it causes a mainly multiplicative decrease of the visual responses and a slight increase in the stimulus-selective response latency. Moreover, serotonin neither systematically changes the selectivity or variability of the response, nor the interneuronal correlation unexplained by the stimulus ("noise-correlation"). The modulation by serotonin has qualitative similarities with that for a decrease in stimulus contrast, but differs quantitatively from decreasing contrast. It can be captured by a simple additive change to a threshold-linear spiking nonlinearity. Together, our results show that serotonin is well suited to control the response gain of neurons in V1 depending on the animal's behavioral or motivational context, complementing other known state-dependent gain-control mechanisms. SIGNIFICANCE STATEMENT Serotonin is an important neuromodulator in the brain and a major target for drugs used to treat psychiatric disorders. Nonetheless, surprisingly little is known about how it shapes information processing in sensory areas. Here we examined the serotonergic modulation of visual processing in the primary visual cortex of awake behaving macaque monkeys. We found that serotonin mainly decreased the gain of the visual responses, without systematically changing their selectivity, variability, or covariability. This

  6. No-scalpel vasectomy by electrocauterization in free range rhesus macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    A. Raj

    2012-02-01

    Full Text Available The objective of the study was to standardize a new method of vasectomy in male rhesus macaques (Macaca mulatta. A total of 208 free range male rhesus macaques captured from different locations in Shivalik Hills in a population control programme of the rhesus macaques in India. General anaesthesia was achieved by using a combination of ketamine hydrochloride at 8 mg/kg body weight and xylazine hydrochloride at 2mg/kg body weight intramuscularly in squeeze cage. Surgical procedure of vasectomy was carried out by single-hole no-scalpel technique using a single pre-scrotal skin incision above the median raphae. Spermatic cord was grasped with ringed forceps and was pulled out through the single-hole incision. Vas deferens was separated from the artery-vein complexus and about 3-4 cm portion of vas deferens was resected. Cauterization of both ends of the vas deferens was achieved with electrocautery. The induction time for anaesthesia was 1.40±0.18 min while surgical time for vasectomy was found to be 5.09±0.22 min. Recovery from general anaesthesia was without side-effects after a mean duration of 36.07±1.22 min, whereas the duration of anaesthesia was observed to be 82.27±4.96 min. There were no major complications following the surgery and recovery of animals was smooth. Animals were kept in postoperative care for five days and released at the same capturing site.

  7. Intermittent pair-housing, pair relationship qualities, and HPA activity in adult female rhesus macaques.

    Science.gov (United States)

    Hannibal, Darcy L; Cassidy, Lauren C; Vandeleest, Jessica; Semple, Stuart; Barnard, Allison; Chun, Katie; Winkler, Sasha; McCowan, Brenda

    2018-05-02

    Laboratory rhesus macaques are often housed in pairs and may be temporarily or permanently separated for research, health, or management reasons. While both long-term social separations and introductions can stimulate a stress response that impacts inflammation and immune function, the effects of short-term overnight separations and whether qualities of the pair relationship mediate these effects are unknown. In this study, we investigated the effects of overnight separations on the urinary cortisol concentration of 20 differentially paired adult female rhesus macaques (Macaca mulatta) at the California National Primate Research Center. These females were initially kept in either continuous (no overnight separation) or intermittent (with overnight separation) pair-housing and then switched to the alternate pair-housing condition part way through the study. Each study subject was observed for 5 weeks, during which we collected measures of affiliative, aggressive, anxious, abnormal, and activity-state behaviors in both pair-housing conditions. Additionally, up to three urine samples were collected from each subject per week and assayed for urinary free cortisol and creatinine. Lastly, the behavioral observer scored each pair on four relationship quality attributes ("Anxious," "Tense," "Well-meshed," and "Friendly") using a seven-point scale. Data were analyzed using a generalized linear model with gamma distribution and an information theoretic approach to determine the best model set. An interaction between the intermittent pairing condition and tense pair adjective rating was in the top three models of the best model set. Dominance and rates of affiliation were also important for explaining urinary cortisol variation. Our results suggest that to prevent significant changes in HPA-axis activation in rhesus macaque females, which could have unintended effects on research outcomes, pairs with "Tense" relationships and overnight separations preventing tactile contact

  8. Macaque homologs of EBV and KSHV show uniquely different associations with simian AIDS-related lymphomas.

    Directory of Open Access Journals (Sweden)

    A Gregory Bruce

    Full Text Available Two gammaherpesviruses, Epstein-Barr virus (EBV (Lymphocryptovirus genus and Kaposi's sarcoma-associated herpesvirus (KSHV (Rhadinovirus genus have been implicated in the etiology of AIDS-associated lymphomas. Homologs of these viruses have been identified in macaques and other non-human primates. In order to assess the association of these viruses with non-human primate disease, archived lymphoma samples were screened for the presence of macaque lymphocryptovirus (LCV homologs of EBV, and macaque rhadinoviruses belonging to the RV1 lineage of KSHV homologs or the more distant RV2 lineage of Old World primate rhadinoviruses. Viral loads were determined by QPCR and infected cells were identified by immunolabeling for different viral proteins. The lymphomas segregated into three groups. The first group (n = 6 was associated with SIV/SHIV infections, contained high levels of LCV (1-25 genomes/cell and expressed the B-cell antigens CD20 or BLA.36. A strong EBNA-2 signal was detected in the nuclei of the neoplastic cells in one of the LCV-high lymphomas, indicative of a type III latency stage. None of the lymphomas in this group stained for the LCV viral capsid antigen (VCA lytic marker. The second group (n = 5 was associated with D-type simian retrovirus-2 (SRV-2 infections, contained high levels of RV2 rhadinovirus (9-790 genomes/cell and expressed the CD3 T-cell marker. The third group (n = 3 was associated with SIV/SHIV infections, contained high levels of RV2 rhadinovirus (2-260 genomes/cell and was negative for both CD20 and CD3. In both the CD3-positive and CD3/CD20-negative lymphomas, the neoplastic cells stained strongly for markers of RV2 lytic replication. None of the lymphomas had detectable levels of retroperitoneal fibromatosis herpesvirus (RFHV, the macaque RV1 homolog of KSHV. Our data suggest etiological roles for both lymphocryptoviruses and RV2 rhadinoviruses in the development of simian AIDS-associated lymphomas and indicate that

  9. Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex

    Science.gov (United States)

    Smiley, John F.; Schroeder, Charles E.

    2017-01-01

    Prior studies have reported “local” field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be “contaminated” by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such “far-field” activity, in addition to, or in absence of, local synaptic responses. SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is

  10. Sexual signalling in female crested macaques and the evolution of primate fertility signals.

    Science.gov (United States)

    Higham, James P; Heistermann, Michael; Saggau, Carina; Agil, Muhammad; Perwitasari-Farajallah, Dyah; Engelhardt, Antje

    2012-06-18

    Female signals of fertility have evolved in diverse taxa. Among the most interesting study systems are those of multimale multifemale group-living primates, where females signal fertility to males through multiple signals, and in which there is substantial inter-specific variation in the composition and reliability of such signals. Among the macaques, some species display reliable behavioural and/or anogenital signals while others do not. One cause of this variation may be differences in male competitive regimes: some species show marked sexual dimorphism and reproductive skew, with males fighting for dominance, while others show low dimorphism and skew, with males queuing for dominance. As such, there is variation in the extent to which rank is a reliable proxy for male competitiveness, which may affect the extent to which it is in females' interest to signal ovulation reliably. However, data on ovulatory signals are absent from species at one end of the macaque continuum, where selection has led to high sexual dimorphism and male reproductive skew. Here we present data from 31 cycles of 19 wild female crested macaques, a highly sexually dimorphic species with strong mating skew. We collected measures of ovarian hormone data from faeces, sexual swelling size from digital images, and male and female behaviour. We show that both sexual swelling size and female proceptivity are graded-signals, but relatively reliable indicators of ovulation, with swelling size largest and female proceptive behaviours most frequent around ovulation. Sexual swelling size was also larger in conceptive cycles. Male mating behaviour was well timed to female ovulation, suggesting that males had accurate information about this. Though probabilistic, crested macaque ovulatory signals are relatively reliable. We argue that in species where males fight over dominance, male dominance rank is surrogate for competitiveness. Under these circumstances it is in the interest of females to increase

  11. Sexual signalling in female crested macaques and the evolution of primate fertility signals

    Directory of Open Access Journals (Sweden)

    Higham James P

    2012-06-01

    Full Text Available Abstract Background Female signals of fertility have evolved in diverse taxa. Among the most interesting study systems are those of multimale multifemale group-living primates, where females signal fertility to males through multiple signals, and in which there is substantial inter-specific variation in the composition and reliability of such signals. Among the macaques, some species display reliable behavioural and/or anogenital signals while others do not. One cause of this variation may be differences in male competitive regimes: some species show marked sexual dimorphism and reproductive skew, with males fighting for dominance, while others show low dimorphism and skew, with males queuing for dominance. As such, there is variation in the extent to which rank is a reliable proxy for male competitiveness, which may affect the extent to which it is in females’ interest to signal ovulation reliably. However, data on ovulatory signals are absent from species at one end of the macaque continuum, where selection has led to high sexual dimorphism and male reproductive skew. Here we present data from 31 cycles of 19 wild female crested macaques, a highly sexually dimorphic species with strong mating skew. We collected measures of ovarian hormone data from faeces, sexual swelling size from digital images, and male and female behaviour. Results We show that both sexual swelling size and female proceptivity are graded-signals, but relatively reliable indicators of ovulation, with swelling size largest and female proceptive behaviours most frequent around ovulation. Sexual swelling size was also larger in conceptive cycles. Male mating behaviour was well timed to female ovulation, suggesting that males had accurate information about this. Conclusion Though probabilistic, crested macaque ovulatory signals are relatively reliable. We argue that in species where males fight over dominance, male dominance rank is surrogate for competitiveness. Under these

  12. Separate value comparison and learning mechanisms in macaque medial and lateral orbitofrontal cortex

    OpenAIRE

    Noonan, M. P.; Walton, M. E.; Behrens, T. E. J.; Sallet, J.; Buckley, M. J.; Rushworth, M. F. S.

    2010-01-01

    Uncertainty about the function of orbitofrontal cortex (OFC) in guiding decision-making may be a result of its medial (mOFC) and lateral (lOFC) divisions having distinct functions. Here we test the hypothesis that the mOFC is more concerned with reward-guided decision making, in contrast with the lOFC's role in reward-guided learning. Macaques performed three-armed bandit tasks and the effects of selective mOFC lesions were contrasted against lOFC lesions. First, we present analyses that make...

  13. Shigella flexneri infection in a newly acquired rhesus macaque (Macaca mulatta)

    OpenAIRE

    Lee, Jae-Il; Kim, Sang-Joon; Park, Chung-Gyu

    2011-01-01

    A 3.4 year-old rhesus macaque weighing 4.5 kg, was suffering from anorexia, acute mucous and bloody diarrhea. On physical examination, the monkey showed a loss of activity, hunched posture, abdominal pain, dehydration, mild gingivitis and unclean anus with discharge. Whole blood was collected for the examination of electrolytes, hematology and serum chemistry; fresh stool was also collected for bacterial culture. Blood profiles showed leukocytosis (14.5 K/?L) and neutrophilia (11.0 K/?L) on c...

  14. Short-term costs and benefits of grooming in Japanese macaques.

    Science.gov (United States)

    Schino, Gabriele; Alessandrini, Alessandro

    2015-07-01

    This study investigated the short-term consequences of giving grooming in Japanese macaques (Macaca fuscata) in order to obtain information on its immediate costs and benefits. Giving grooming was associated with increased aggression received from groomees and decreased aggression received from third parties (but only as long as the groomer maintained proximity to the groomee). Grooming was also associated with decreased scratching rates. These results emphasize the unpredictable outcome of individual grooming interactions and the difficulties of social decision-making for monkeys living in despotic societies.

  15. Vaccine decision-making begins in pregnancy: Correlation between vaccine concerns, intentions and maternal vaccination with subsequent childhood vaccine uptake.

    Science.gov (United States)

    Danchin, M H; Costa-Pinto, J; Attwell, K; Willaby, H; Wiley, K; Hoq, M; Leask, J; Perrett, K P; O'Keefe, Jacinta; Giles, M L; Marshall, H

    2017-08-12

    Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-valuepost delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake. First time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy for all mothers in pregnancy and post delivery, particularly first-time mothers. Copyright © 2017 Elsevier Ltd

  16. Human Papillomavirus (HPV) Vaccines

    Science.gov (United States)

    ... factors for developing them, such as taking oral contraceptives . A safety review of Gardasil in Denmark and ... and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark ...

  17. [Development of new vaccines].

    Science.gov (United States)

    González-Romo, Fernando; Picazo, Juan J

    2015-10-01

    Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost. There are currently more than 130 vaccines are under development against the more wished (malaria or HIV), difficult to get (CMV or RSV), severe re-emerging (Dengue or Ebola), increasing importance (Chagas disease or Leishmania), and nosocomial emerging (Clostridium difficile or Staphylococcus aureus) infectious diseases. Copyright © 2015. Published by Elsevier España, S.L.U.

  18. Ingredients of Vaccines

    Science.gov (United States)

    ... containing preservative that is added to vials of vaccine that contain more than one dose to prevent contamination and growth of potentially harmful bacteria. For children with a prior history of allergic reactions to any of these substances ...

  19. Current status of rotavirus vaccines.

    Science.gov (United States)

    Wang, Ching-Min; Chen, Shou-Chien; Chen, Kow-Tong

    2015-11-01

    Rotaviruses remain the major cause of childhood diarrheal disease worldwide and of diarrheal deaths of infants and children in developing countries. The huge burden of childhood rotavirus-related diarrhea in the world continues to drive the remarkable pace of vaccine development. Research articles were searched using terms "rotavirus" and "rotavirus vaccine" in MEDLINE and PubMed. Articles not published in the English language, articles without abstracts, and opinion articles were excluded from the review. After preliminary screening, all articles were reviewed and synthesized to provide an overview of current vaccines and vaccination programs. In this review of the global rotavirus vaccines and vaccination programs, the principles of rotavirus vaccine development and the efficacy of the currently licensed vaccines from both developed and developing countries were summarized. Rotavirus is a common cause of diarrhea in children in both developed and developing countries. Rotavirus vaccination is a cost-effective measure to prevent rotavirus diarrhea.

  20. Vaccines for Older Adults.

    Science.gov (United States)

    Worz, Chad; Martin, Caren McHenry; Travis, Catherine

    2017-09-01

    Several vaccine-preventable diseases-influenza, pneumonia, herpes zoster, and pertussis-threaten the health of older adults in the United States. Both the costs associated with treating these diseases and the potential to increase morbidity and mortality are high for this patient population. Pharmacists and other health care professionals play a significant role in ensuring the elderly patient receives the recommended vaccines at the recommended intervals.

  1. Beninese vaccination clinic

    OpenAIRE

    Linda Sun

    2017-01-01

    This photo was taken in the village of Ladji, which is on the outskirts of Cotonou, the capital of Benin. At the time, I was a second year medical student volunteering at a local medical clinic. On every Wednesday morning, many Beninese babies, like this one, cry out of discomfort while receiving their monthly vaccinations. The photo shows a local clinic nurse administering the vaccination.

  2. Beninese vaccination clinic

    Directory of Open Access Journals (Sweden)

    Linda Sun

    2017-04-01

    Full Text Available This photo was taken in the village of Ladji, which is on the outskirts of Cotonou, the capital of Benin. At the time, I was a second year medical student volunteering at a local medical clinic. On every Wednesday morning, many Beninese babies, like this one, cry out of discomfort while receiving their monthly vaccinations. The photo shows a local clinic nurse administering the vaccination.

  3. HPV vaccines: a controversial issue?

    Science.gov (United States)

    Nicol, A F; Andrade, C V; Russomano, F B; Rodrigues, L L S; Oliveira, N S; Provance, D W

    2016-01-01

    Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

  4. Epilepsy and vaccinations: Italian guidelines.

    Science.gov (United States)

    Pruna, Dario; Balestri, Paolo; Zamponi, Nelia; Grosso, Salvatore; Gobbi, Giuseppe; Romeo, Antonino; Franzoni, Emilio; Osti, Maria; Capovilla, Giuseppe; Longhi, Riccardo; Verrotti, Alberto

    2013-10-01

    Reports of childhood epilepsies in temporal association with vaccination have had a great impact on the acceptance of vaccination programs by health care providers, but little is known about this possible temporal association and about the types of seizures following vaccinations. For these reasons the Italian League Against Epilepsy (LICE), in collaboration with other Italian scientific societies, has decided to generate Guidelines on Vaccinations and Epilepsy. The aim of Guidelines on Vaccinations and Epilepsy is to present recent unequivocal evidence from published reports on the possible relationship between vaccines and epilepsy in order to provide information about contraindications and risks of vaccinations in patients with epilepsy. The following main issues have been addressed: (1) whether contraindications to vaccinations exist in patients with febrile convulsions, epilepsy, and/or epileptic encephalopathies; and (2) whether any vaccinations can cause febrile seizures, epilepsy, and/or epileptic encephalopathies. Diphtheria-tetanus-pertussis (DTP) vaccination and measles, mumps, and rubella vaccination (MMR) increase significantly the risk of febrile seizures. Recent observations and data about the relationships between vaccination and epileptic encephalopathy show that some cases of apparent vaccine-induced encephalopathy could in fact be caused by an inherent genetic defect with no causal relationship with vaccination. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  5. HPV vaccines: a controversial issue?

    Directory of Open Access Journals (Sweden)

    A.F. Nicol

    2016-01-01

    Full Text Available Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

  6. A Multiplex Microsphere-Based Immunoassay Increases the Sensitivity of SIV-Specific Antibody Detection in Serum Samples and Mucosal Specimens Collected from Rhesus Macaques Infected with SIVmac239.

    Science.gov (United States)

    Powell, Rebecca L R; Ouellette, Ian; Lindsay, Ross W; Parks, Christopher L; King, C Richter; McDermott, Adrian B; Morrow, Gavin

    2013-06-01

    Results from recent HIV-1 vaccine studies have indicated that high serum antibody (Ab) titers may not be necessary for Ab-mediated protection, and that Abs localized to mucosal sites might be critical for preventing infection. Enzyme-linked immunosorbent assay (ELISA) has been used for decades as the gold standard for Ab measurement, though recently, highly sensitive microsphere-based assays have become available, with potential utility for improved detection of Abs. In this study, we assessed the Bio-Plex(®) Suspension Array System for the detection of simian immunodeficiency virus (SIV)-specific Abs in rhesus macaques (RMs) chronically infected with SIV, whose serum or mucosal SIV-specific Ab titers were negative by ELISA. We developed a SIVmac239-specific 4-plex bead array for the simultaneous detection of Abs binding to Env, Gag, Pol, and Nef. The 4-plex assay was used to quantify SIV-specific serum IgG and rectal swab IgA titers from control (SIV-naive) and SIVmac239-infected RMs. The Bio-Plex assay specifically detected anti-SIV Abs in specimens from SIV-infected animals for all four analytes when compared to SIV-naive control samples (p≤0.04). Furthermore, in 70% of Env and 79% of Gag ELISA-negative serum samples, specific Ab was detected using the Bio-Plex assay. Similarly, 71% of Env and 48% of Gag ELISA-negative rectal swab samples were identified as positive using the Bio-Plex assay. Importantly, assay specificity (i.e., probability of true positives) was comparable to ELISA (94%-100%). The results reported here indicate that microsphere-based methods provide a substantial improvement over ELISA for the detection of Ab responses, aid in detecting specific Abs when analyzing samples containing low levels of Abs, such as during the early stages of a vaccine trial, and may be valuable in attempts to link protective efficacy of vaccines with induced Ab responses.

  7. Mathematical modeling of ultradeep sequencing data reveals that acute CD8+ T-lymphocyte responses exert strong selective pressure in simian immunodeficiency virus-infected macaques but still fail to clear founder epitope sequences.

    Science.gov (United States)

    Love, Tanzy M T; Thurston, Sally W; Keefer, Michael C; Dewhurst, Stephen; Lee, Ha Youn

    2010-06-01

    The prominent role of antiviral cytotoxic CD8(+) T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and SIV) has rationalized the development of T-cell-based vaccines. However, the presence of escape mutations in the acute stage of infection has raised a concern that accelerated escape from vaccine-induced CD8-TL responses might undermine vaccine efficacy. We reanalyzed previously published data of 101,822 viral genomes of three CD8-TL epitopes, Nef(103-111)RM9 (RM9), Tat(28-35)SL8 (SL8), and Gag(181-189)CM9 (CM9), sampled by ultradeep pyrosequencing from eight macaques. Multiple epitope variants appeared during the resolution of acute viremia, followed by the predominance of a single mutant epitope. By fitting a mathematical model, we estimated the first acute escape rate as 0.36 day(-1) within escape-prone epitopes, RM9 and SL8, and the chronic escape rate as 0.014 day(-1) within the CM9 epitope. Our estimate of SIV acute escape rates was found to be comparable to very early HIV-1 escape rates. The timing of the first escape was more highly correlated with the timing of the peak CD8-TL response than with the magnitude of the CD8-TL response. The transmitted epitope decayed more than 400 times faster during the acute viral decline stage than predicted by a neutral evolution model. However, the founder epitope persisted as a minor population even at the viral set point; in contrast, the majority of acute escape epitopes were completely cleared. Our results suggest that a reservoir of SIV infection is preferentially formed by virus with the transmitted epitope.

  8. Superior induction of T cell responses to conserved HIV-1 regions by electroporated alphavirus replicon DNA compared to that with conventional plasmid DNA vaccine.

    Science.gov (United States)

    Knudsen, Maria L; Mbewe-Mvula, Alice; Rosario, Maximillian; Johansson, Daniel X; Kakoulidou, Maria; Bridgeman, Anne; Reyes-Sandoval, Arturo; Nicosia, Alfredo; Ljungberg, Karl; Hanke, Tomás; Liljeström, Peter

    2012-04-01

    Vaccination using "naked" DNA is a highly attractive strategy for induction of pathogen-specific immune responses; however, it has been only weakly immunogenic in humans. Previously, we constructed DNA-launched Semliki Forest virus replicons (DREP), which stimulate pattern recognition receptors and induce augmented immune responses. Also, in vivo electroporation was shown to enhance immune responses induced by conventional DNA vaccines. Here, we combine these two approaches and show that in vivo electroporation increases CD8(+) T cell responses induced by DREP and consequently decreases the DNA dose required to induce a response. The vaccines used in this study encode the multiclade HIV-1 T cell immunogen HIVconsv, which is currently being evaluated in clinical trials. Using intradermal delivery followed by electroporation, the DREP.HIVconsv DNA dose could be reduced to as low as 3.2 ng to elicit frequencies of HIV-1-specific CD8(+) T cells comparable to those induced by 1 μg of a conventional pTH.HIVconsv DNA vaccine, representing a 625-fold molar reduction in dose. Responses induced by both DREP.HIVconsv and pTH.HIVconsv were further increased by heterologous vaccine boosts employing modified vaccinia virus Ankara MVA.HIVconsv and attenuated chimpanzee adenovirus ChAdV63.HIVconsv. Using the same HIVconsv vaccines, the mouse observations were supported by an at least 20-fold-lower dose of DNA vaccine in rhesus macaques. These data point toward a strategy for overcoming the low immunogenicity of DNA vaccines in humans and strongly support further development of the DREP vaccine platform for clinical evaluation.

  9. Key Facts about Seasonal Flu Vaccine

    Science.gov (United States)

    ... Swine Variant Pandemic Other Key Facts About Seasonal Flu Vaccine Language: English (US) Español Recommend on Facebook ... the flu is to get vaccinated each year. Flu Vaccination Why should people get vaccinated against the ...

  10. Meningococcal group B vaccines.

    Science.gov (United States)

    Findlow, Jamie

    2013-06-01

    Meningococcal disease remains a devastating and feared infection with a significant morbidity and mortality profile. The successful impact of meningococcal capsular group C glyconconjugate vaccines introduced into the UK infant immunization schedule in 1999, has resulted in >80% of disease now being attributable to meningococcal capsular group B (MenB). MenB glyconconjugate vaccines are not immunogenic and hence, vaccine design has focused on sub-capsular antigens. Recently, a four component vaccine to combat MenB disease (4CMenB) has progressed through clinical development and was approved by the European Medicines Agency at the end of 2012. This vaccine has proven safe and immunogenic and has been predicted to provide protection against ~73% of the MenB disease from England and Wales. Recommendation/implementation of the vaccine into the UK infant schedule is currently being evaluated. 4CMenB has the potential to provide protection against a significant proportion of MenB disease in the UK which is currently unpreventable.

  11. Genome-derived vaccines.

    Science.gov (United States)

    De Groot, Anne S; Rappuoli, Rino

    2004-02-01

    Vaccine research entered a new era when the complete genome of a pathogenic bacterium was published in 1995. Since then, more than 97 bacterial pathogens have been sequenced and at least 110 additional projects are now in progress. Genome sequencing has also dramatically accelerated: high-throughput facilities can draft the sequence of an entire microbe (two to four megabases) in 1 to 2 days. Vaccine developers are using microarrays, immunoinformatics, proteomics and high-throughput immunology assays to reduce the truly unmanageable volume of information available in genome databases to a manageable size. Vaccines composed by novel antigens discovered from genome mining are already in clinical trials. Within 5 years we can expect to see a novel class of vaccines composed by genome-predicted, assembled and engineered T- and Bcell epitopes. This article addresses the convergence of three forces--microbial genome sequencing, computational immunology and new vaccine technologies--that are shifting genome mining for vaccines onto the forefront of immunology research.

  12. Effects of MVA85A vaccine on tuberculosis challenge in animals: systematic review

    Science.gov (United States)

    Kashangura, Rufaro; Sena, Emily S; Young, Taryn; Garner, Paul

    2015-01-01

    Background: The existing Bacillus Calmette–Guérin (BCG) vaccination provides partial protection against tuberculosis (TB). The modified vaccinia ankara virus-expressing antigen 85A (MVA85A) aims to boost BCG immunity. We evaluated the animal evidence supporting the testing of MVA85A in humans. Methods: Our protocol included in vivo preclinical studies of the MVA85A booster with BCG compared with BCG alone, followed by a TB challenge. We used standard methods for systematic review of animal studies, and summarized mortality, measures of pathology and lung bacterial load. The comprehensive literature search was to September 2014. Two independent investigators assessed eligibility and performed data extraction. We assessed study quality and pooled bacteria load using random effect meta-analysis. Findings: We included eight studies in 192 animals. Three experiments were in mice, two in guinea pigs, two in macaques and one in calves. Overall, study quality was low with no randomization, baseline comparability not described and blinding not reported. For animal death (including euthanasia due to severe morbidity), studies were underpowered, and overall no benefit demonstrated. No difference was shown for lung pathology measured on an ordinal scale or bacterial load. The largest mortality trial carried out in macaques had more deaths in the MVA85A vaccine group, and was published after a trial in South Africa had started recruiting children. Conclusions: This independent assessment of the animal data does not provide evidence to support efficacy of MVA85A as a BCG booster. More rigorous conduct and reporting of preclinical research are warranted, and we believe the results of studies should be publicly available before embarking on trials in humans, irrespective of the findings. PMID:26351306

  13. How influenza vaccination policy may affect vaccine logistics.

    Science.gov (United States)

    Assi, Tina-Marie; Rookkapan, Korngamon; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T; Welling, Joel S; Norman, Bryan A; Connor, Diana L; Chen, Sheng-I; Slayton, Rachel B; Laosiritaworn, Yongjua; Wateska, Angela R; Wisniewski, Stephen R; Lee, Bruce Y

    2012-06-22

    When policymakers make decision about the target populations and timing of influenza vaccination, they may not consider the impact on the vaccine supply chains, which may in turn affect vaccine availability. Our goal is to explore the effects on the Thailand vaccine supply chain of introducing influenza vaccines and varying the target populations and immunization time-frames. We Utilized our custom-designed software HERMES (Highly Extensible Resource for Modeling Supply Chains), we developed a detailed, computational discrete-event simulation model of the Thailand's National Immunization Program (NIP) supply chain in Trang Province, Thailand. A suite of experiments simulated introducing influenza vaccines for different target populations and over different time-frames prior to and during the annual influenza season. Introducing influenza vaccines creates bottlenecks that reduce the availability of both influenza vaccines as well as the other NIP vaccines, with provincial to district transport capacity being the primary constraint. Even covering only 25% of the Advisory Committee on Immunization Practice-recommended population while administering the vaccine over six months hinders overall vaccine availability so that only 62% of arriving patients can receive vaccines. Increasing the target population from 25% to 100% progressively worsens these bottlenecks, while increasing influenza vaccination time-frame from 1 to 6 months decreases these bottlenecks. Since the choice of target populations for influenza vaccination and the time-frame to deliver this vaccine can substantially affect the flow of all vaccines, policy-makers may want to consider supply chain effects when choosing target populations for a vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Glycoconjugate Vaccines: The Regulatory Framework.

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    Jones, Christopher

    2015-01-01

    Most vaccines, including the currently available glycoconjugate vaccines, are administered to healthy infants, to prevent future disease. The safety of a prospective vaccine is a key prerequisite for approval. Undesired side effects would not only have the potential to damage the individual infant but also lead to a loss of confidence in the respective vaccine-or vaccines in general-on a population level. Thus, regulatory requirements, particularly with regard to safety, are extremely rigorous. This chapter highlights regulatory aspects on carbohydrate-based vaccines with an emphasis on analytical approaches to ensure the consistent quality of successive manufacturing lots.

  15. Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression.

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    For Yue Tso

    Full Text Available A better understanding of how the biological functions of the HIV-1 envelope (Env changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection of macaque with SHIV, expressing HIV-1 clade C Env V1-V5 region. By using this model, we examined the changes in biological functions of Env in the infected animal over the entire disease course. Our data showed an increase in the neutralization resistance phenotype over time and coincided with the decrease in the net charges of the V1-V5 region. Infection of PBMC with provirus expressing various Env clones, isolated from the infected animal over time, showed a surprisingly better replicative fitness for viruses expressing the Env from early time point. Biotinylation and ELISA data also indicated a decrease of cell-surface-associated Env and virion-associated gp120 content with disease progression. This decrease did not affect the CD4-binding capability of Env, but were positively correlated with the decrease of Env fusion ability. Interestingly, some of these changes in biological functions reverted to the pre-AIDS level during advance AIDS. These data suggested a dynamic relationship between the Env V1-V5 region with the host immune pressure. The observed changes of biological functions in this setting might reflect and predict those occurring during natural disease progression in human.

  16. Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Env-specific antibody response in SHIV-infected rhesus macaques.

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    Juan Pablo Jaworski

    Full Text Available Our central hypothesis is that protection against HIV infection will be powerfully influenced by the magnitude and quality of the B cell response. Although sterilizing immunity, mediated by pre-formed abundant and potent antibodies is the ultimate goal for B cell-targeted HIV vaccine strategies, scenarios that fall short of this may still confer beneficial defenses against viremia and disease progression. We evaluated the impact of sub-sterilizing pre-existing neutralizing antibody on the B cell response to SHIV infection. Adult male rhesus macaques received passive transfer of a sub-sterilizing amount of polyclonal neutralizing immunoglobulin (Ig purified from previously infected animals (SHIVIG or control Ig prior to intra-rectal challenge with SHIVSF162P4 and extensive longitudinal sampling was performed. SHIVIG treated animals exhibited significantly reduced viral load and increased de novo Env-specific plasma antibody. Dysregulation of the B cell profile was grossly apparent soon after infection in untreated animals; exemplified by a ≈50% decrease in total B cells in the blood evident 2-3 weeks post-infection which was not apparent in SHIVIG treated animals. IgD+CD5+CD21+ B cells phenotypically similar to marginal zone-like B cells were highly sensitive to SHIV infection, becoming significantly decreased as early as 3 days post-infection in control animals, while being maintained in SHIVIG treated animals, and were highly correlated with the induction of Env-specific plasma antibody. These results suggest that B cell dysregulation during the early stages of infection likely contributes to suboptimal Env-specific B cell and antibody responses, and strategies that limit this dysregulation may enhance the host's ability to eliminate HIV.

  17. A novel protective MHC-I haplotype not associated with dominant Gag-specific CD8+ T-cell responses in SIVmac239 infection of Burmese rhesus macaques.

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    Naofumi Takahashi

    Full Text Available Several major histocompatibility complex class I (MHC-I alleles are associated with lower viral loads and slower disease progression in human immunodeficiency virus (HIV and simian immunodeficiency virus (SIV infections. Immune-correlates analyses in these MHC-I-related HIV/SIV controllers would lead to elucidation of the mechanism for viral control. Viral control associated with some protective MHC-I alleles is attributed to CD8+ T-cell responses targeting Gag epitopes. We have been trying to know the mechanism of SIV control in multiple groups of Burmese rhesus macaques sharing MHC-I genotypes at the haplotype level. Here, we found a protective MHC-I haplotype, 90-010-Id (D, which is not associated with dominant Gag-specific CD8+ T-cell responses. Viral loads in five D+ animals became significantly lower than those in our previous cohorts after 6 months. Most D+ animals showed predominant Nef-specific but not Gag-specific CD8+ T-cell responses after SIV challenge. Further analyses suggested two Nef-epitope-specific CD8+ T-cell responses exerting strong suppressive pressure on SIV replication. Another set of five D+ animals that received a prophylactic vaccine using a Gag-expressing Sendai virus vector showed significantly reduced viral loads compared to unvaccinated D+ animals at 3 months, suggesting rapid SIV control by Gag-specific CD8+ T-cell responses in addition to Nef-specific ones. These results present a pattern of SIV control with involvement of non-Gag antigen-specific CD8+ T-cell responses.

  18. MiniCD4 microbicide prevents HIV infection of human mucosal explants and vaginal transmission of SHIV(162P3 in cynomolgus macaques.

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    Nathalie Dereuddre-Bosquet

    Full Text Available In complement to an effective vaccine, development of potent anti-HIV microbicides remains an important priority. We have previously shown that the miniCD4 M48U1, a functional mimetic of sCD4 presented on a 27 amino-acid stable scaffold, inhibits a broad range of HIV-1 isolates at sub-nanomolar concentrations in cellular models. Here, we report that M48U1 inhibits efficiently HIV-1(Ba-L in human mucosal explants of cervical and colorectal tissues. In vivo efficacy of M48U1 was evaluated in nonhuman primate (NHP model of mucosal challenge with SHIV(162P3 after assessing pharmacokinetics and pharmacodynamics of a miniCD4 gel formulation in sexually matured female cynomolgus macaques. Among 12 females, half were treated with hydroxyethylcellulose-based gel (control, the other half received the same gel containing 3 mg/g of M48U1, one hour before vaginal route challenge with 10 AID(50 of SHIV(162P3. All control animals were infected with a peak plasma viral load of 10(5-10(6 viral RNA (vRNA copies per mL. In animals treated with miniCD4, 5 out of 6 were fully protected from acquisition of infection, as assessed by qRT-PCR for vRNA detection in plasma, qPCR for viral DNA detection in PBMC and lymph node cells. The only infected animal in this group had a delayed peak of viremia of one week. These results demonstrate that M48U1 miniCD4 acts in vivo as a potent entry inhibitor, which may be considered in microbicide developments.

  19. The influence of age on wild rhesus macaques' affiliative social interactions.

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    Liao, Zhijie; Sosa, Sebastian; Wu, Chengfeng; Zhang, Peng

    2018-02-01

    The social relationships that individuals experience at different life stages have a non-negligible influence on their lives, and this is particularly true for group living animals. The long lifespan of many primates makes it likely that these animals have various tactics of social interaction to adapt to complex changes in environmental or physical conditions. The different strategies used in social interaction by individuals at different life stages, and whether the position (central or peripheral) or role (initiator or recipient) of an individual in the group social network changes with age, are intriguing questions that remain to be investigated. We used social network analysis to examine age-related differences in social interaction patterns, social roles, and social positions in three affiliative social networks (approach, allogrooming, and social play) in a group of wild rhesus macaques (Macaca mulatta). Our results showed that social interaction patterns of rhesus macaques differ between age classes in the following ways: i) young individuals tend to allocate social time to a high number of groupmates, older individuals prefer to focus on fewer, specific partners; ii) as they grow older, individuals tend to be recipients in approach interactions and initiators in grooming interactions; and iii) regardless of the different social interaction strategies, individuals of all ages occupy a central position in the group. These results reveal a possible key role played by immature individuals in group social communication, a little-explored issue which deserves closer investigation in future research. © 2017 Wiley Periodicals, Inc.

  20. An effort to use human-based exome capture methods to analyze chimpanzee and macaque exomes.

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    Xin Jin

    Full Text Available Non-human primates have emerged as an important resource for the study of human disease and evolution. The characterization of genomic variation between and within non-human primate species could advance the development of genetically defined non-human primate disease models. However, non-human primate specific reagents that would expedite such research, such as exon-capture tools, are lacking. We evaluated the efficiency of using a human exome capture design for the selective enrichment of exonic regions of non-human primates. We compared the exon sequence recovery in nine chimpanzees, two crab-eating macaques and eight Japanese macaques. Over 91% of the target regions were captured in the non-human primate samples, although the specificity of the capture decreased as evolutionary divergence from humans increased. Both intra-specific and inter-specific DNA variants were identified; Sanger-based resequencing validated 85.4% of 41 randomly selected SNPs. Among the short indels identified, a majority (54.6%-77.3% of the variants resulted in a change of 3 base pairs, consistent with expectations for a selection against frame shift mutations. Taken together, these findings indicate that use of a human design exon-capture array can provide efficient enrichment of non-human primate gene regions. Accordingly, use of the human exon-capture methods provides an attractive, cost-effective approach for the comparative analysis of non-human primate genomes, including gene-based DNA variant discovery.

  1. Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques.

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    Meyer, C; Walker, J; Dewane, J; Engelmann, F; Laub, W; Pillai, S; Thomas, Charles R; Messaoudi, I

    2015-09-01

    In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease. © 2015 British Society for Immunology.

  2. Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

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    Cabrera-Mora, Monica; Garcia, AnaPatricia; Orkin, Jack; Strobert, Elizabeth; Barnwell, John W.; Galinski, Mary R.

    2013-01-01

    Severe malaria, a leading cause of mortality among children and nonimmune adults, is a multisystemic disorder characterized by complex clinical syndromes that are mechanistically poorly understood. The interplay of various parasite and host factors is critical in the pathophysiology of severe malaria. However, knowledge regarding the pathophysiological mechanisms and pathways leading to the multisystemic disorders of severe malaria in humans is limited. Here, we systematically investigate infections with Plasmodium coatneyi, a simian malaria parasite that closely mimics the biological characteristics of P. falciparum, and develop baseline data and protocols for studying erythrocyte turnover and severe malaria in greater depth. We show that rhesus macaques (Macaca mulatta) experimentally infected with P. coatneyi develop anemia, coagulopathy, and renal and metabolic dysfunction. The clinical course of acute infections required suppressive antimalaria chemotherapy, fluid support, and whole-blood transfusion, mimicking the standard of care for the management of severe malaria cases in humans. Subsequent infections in the same animals progressed with a mild illness in comparison, suggesting that immunity played a role in reducing the severity of the disease. Our results demonstrate that P. coatneyi infection in rhesus macaques can serve as a highly relevant model to investigate the physiological pathways and molecular mechanisms of malaria pathogenesis in naïve and immune individuals. Together with high-throughput postgenomic technologies, such investigations hold promise for the identification of new clinical interventions and adjunctive therapies. PMID:23509137

  3. Limited SHIV env diversification in macaques failing oral antiretroviral pre-exposure prophylaxis.

    Science.gov (United States)

    Zheng, Qi; Ruone, Susan; Switzer, William M; Heneine, Walid; García-Lerma, J Gerardo

    2012-05-09

    Pre-exposure prophylaxis (PrEP) with daily Truvada [a combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)] is a novel HIV prevention strategy recently found to prevent HIV transmission among men who have sex with men and heterosexual couples. Acute infection in adherent persons who fail PrEP will inevitably occur under concurrent antiretroviral therapy, thus raising questions regarding the potential impact of PrEP on early viral dynamics. We investigated viral evolution dynamics in a macaque model of PrEP consisting of repeated rectal exposures to SHIV162P3 in the presence of PrEP. Four macaques were infected during daily or intermittent PrEP with FTC or FTC/TDF, and five were untreated controls. SHIV env sequence evolution was monitored by single genome amplification with phylogenetic and sequence analysis. Mean nucleotide divergence from transmitted founder viruses calculated 17 weeks (range = 12-20) post peak viremia was significantly lower in PrEP failures than in control animals (7.2 × 10-3 compared to 1.6 × 10-2 nucleotide substitutions per site per year, respectively, p diversification during early infection might enhance immune control by slowing the selection of escape mutants.

  4. An experimental investigation of referential looking in free-ranging Barbary macaques (Macaca sylvanus).

    Science.gov (United States)

    Roberts, Sam G B; McComb, Karen; Ruffman, Ted

    2008-02-01

    The authors examined looking behavior between 15 Barbary macaque (Macaca sylvanus) infants and their mothers in the presence of a rubber snake (experimental period) and in the absence of the snake (control period). Two of the 15 infants looked referentially at their mother in the experimental period. Including both referential and nonreferential looks, the six older infants (aged 5 to 12 months) displayed a higher frequency of looks to mother than nine younger infants (aged 3 to 4.5 months) in the experimental period, but not in the control period. Older infants looked more to the mother in the experimental condition, whereas the younger infants looked more to the mother in the control condition, or looked equally in the two conditions. These results suggest that age is an important factor in determining looking behavior to mother in situations of uncertainty. Compared to hand-reared chimpanzees or human infants tested in standard social referencing paradigms, the infant macaques displayed a low rate of referential looking. Possible explanations for this are discussed. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

  5. An experimental examination of female responses to infant face coloration in rhesus macaques.

    Science.gov (United States)

    Gerald, Melissa S; Waitt, Corri; Maestripieri, Dario

    2006-11-01

    In many primates, infants possess distinctive coloration that changes as a function of age. This colour is thought to serve the purpose of eliciting caretaking behaviour from the mother as well as other conspecifics. The present study investigated the responses of adult female rhesus macaques (Macaca mulatta) to pictures of infant faces in relation to infant age and facial coloration. Study animals were shown digitized images of neonates and 5-6-month-old infants displaying either unaltered facial colour, pink neonatal colour, or novel (green) facial colour. While infant and neonate faces of all colours elicited the attention of adult females, pink neonatal facial coloration did not appear to be especially attractive to subjects in contrast with the findings from an earlier study [Higley, J.D., Hopkins, W.D., Hirsch, R.M. Marra, L.M. Suomi S.J., 1987. Preferences of female rhesus monkeys (Macaca mulatta) for infantile coloration. Dev. Psychobiol. 20, 7-18]. The results suggest that infant facial colour is not particularly important in mediating infant attractiveness to rhesus macaque females as previously suggested or that other infantile facial characteristics might be more important than colour in eliciting caretaking behaviours amongst females.

  6. Decoding target distance and saccade amplitude from population activity in the macaque lateral intraparietal area (LIP

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    Frank Bremmer

    2016-08-01

    Full Text Available Primates perform saccadic eye movements in order to bring the image of an interesting target onto the fovea. Compared to stationary targets, saccades towards moving targets are computationally more demanding since the oculomotor system must use speed and direction information about the target as well as knowledge about its own processing latency to program an adequate, predictive saccade vector. In monkeys, different brain regions have been implicated in the control of voluntary saccades, among them the lateral intraparietal area (LIP. Here we asked, if activity in area LIP reflects the distance between fovea and saccade target, or the amplitude of an upcoming saccade, or both. We recorded single unit activity in area LIP of two macaque monkeys. First, we determined for each neuron its preferred saccade direction. Then, monkeys performed visually guided saccades along the preferred direction towards either stationary or moving targets in pseudo-randomized order. LIP population activity allowed to decode both, the distance between fovea and saccade target as well as the size of an upcoming saccade. Previous work has shown comparable results for saccade direction (Graf and Andersen, 2014a, b. Hence, LIP population activity allows to predict any two-dimensional saccade vector. Functional equivalents of macaque area LIP have been identified in humans. Accordingly, our results provide further support for the concept of activity from area LIP as neural basis for the control of an oculomotor brain-machine interface.

  7. Identification of a Novel Enterovirus Species in Rhesus Macaque in China.

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    Ao, Yuan-Yun; Yu, Jie-Mei; Zhang, Cui-Yuan; Xin, Yun-Yun; Li, Li-Li; Duan, Zhao-Jun

    2016-06-22

    Recent studies of Enterovirus (EV) in nonhuman primates (NHPs), which could act as a source of future emerging human viral diseases, have boosted interest in the search for novel EVs. Here, a highly divergent strain of EV, tentatively named SEV-gx, was identified by viral metagenomic analysis from stool samples of rhesus macaques in China. In total, 27 of 280 (9.6%) faecal samples from rhesus macaques were positive for SEV-gx. Its complete genomic sequence is 7,367 nucleotide (nt). Genomic analyses showed that it has a standard genomic organisation for EVs, being more closely related to EV-J strains (approximately 54.0%, 43.0-44.1%, 52.3-55.2%, 61.1-62.7% and 64.0% amino acids identity in polyprotein, P1, P2 and P3 and combined 2C/3CD regions, respectively). It was also shown to have genome characteristics typical of EVs. Phylogenetic analysis of P1, 2C and 3CD aa indicated that SEV-gx can be classified as a distinct cluster in the EVs. All of this evidence demonstrates SEV-gx is a novel species (tentatively named EV-K) in the EV genus, which contributes to our understanding of the genetic diversity and evolution of EVs. Further studies are needed to investigate the potential pathogenicity of SEV-gx in NHPs and humans.

  8. Detecting instability in animal social networks: genetic fragmentation is associated with social instability in rhesus macaques.

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    Brianne A Beisner

    2011-01-01

    Full Text Available The persistence of biological systems requires evolved mechanisms which promote stability. Cohesive primate social groups are one example of stable biological systems, which persist in spite of regular conflict. We suggest that genetic relatedness and its associated kinship structure are a potential source of stability in primate social groups as kinship structure is an important organizing principle in many animal societies. We investigated the effect of average genetic relatedness per matrilineal family on the stability of matrilineal grooming and agonistic interactions in 48 matrilines from seven captive groups of rhesus macaques. Matrilines with low average genetic relatedness show increased family-level instability such as: more sub-grouping in their matrilineal groom network, more frequent fighting with kin, and higher rates of wounding. Family-level instability in multiple matrilines within a group is further associated with group-level instability such as increased wounding. Stability appears to arise from the presence of clear matrilineal structure in the rhesus macaque group hierarchy, which is derived from cohesion among kin in their affiliative and agonistic interactions with each other. We conclude that genetic relatedness and kinship structure are an important source of group stability in animal societies, particularly when dominance and/or affilative interactions are typically governed by kinship.

  9. Social power, conflict policing, and the role of subordination signals in rhesus macaque society.

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    Beisner, Brianne A; Hannibal, Darcy L; Finn, Kelly R; Fushing, Hsieh; McCowan, Brenda

    2016-05-01

    Policing is a conflict-limiting mechanism observed in many primate species. It is thought to require a skewed distribution of social power for some individuals to have sufficiently high social power to stop others' fights, yet social power has not been examined in most species with policing behavior. We examined networks of subordination signals as a source of social power that permits policing behavior in rhesus macaques. For each of seven captive groups of rhesus macaques, we (a) examined the structure of subordination signal networks and used GLMs to examine the relationship between (b) pairwise dominance certainty and subordination network pathways and (c) policing frequency and social power (group-level convergence in subordination signaling pathways). Networks of subordination signals had perfect linear transitivity, and pairs connected by both direct and indirect pathways of signals had more certain dominance relationships than pairs with no such network connection. Social power calculated using both direct and indirect network pathways showed a heavy-tailed distribution and positively predicted conflict policing. Our results empirically substantiate that subordination signaling is associated with greater dominance relationship certainty and further show that pairs who signal rarely (or not at all) may use information from others' signaling interactions to infer or reaffirm the relative certainty of their own relationships. We argue that the network of formal dominance relationships is central to societal stability because it is important for relationship stability and also supports the additional stabilizing mechanism of policing. © 2016 Wiley Periodicals, Inc.

  10. Responses to social and environmental stress are attenuated by strong male bonds in wild macaques

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    Young, Christopher; Majolo, Bonaventura; Heistermann, Michael; Schülke, Oliver; Ostner, Julia

    2014-01-01

    In humans and obligatory social animals, individuals with weak social ties experience negative health and fitness consequences. The social buffering hypothesis conceptualizes one possible mediating mechanism: During stressful situations the presence of close social partners buffers against the adverse effects of increased physiological stress levels. We tested this hypothesis using data on social (rate of aggression received) and environmental (low temperatures) stressors in wild male Barbary macaques (Macaca sylvanus) in Morocco. These males form strong, enduring, and equitable affiliative relationships similar to human friendships. We tested the effect of the strength of a male’s top three social bonds on his fecal glucocorticoid metabolite (fGCM) levels as a function of the stressors’ intensity. The attenuating effect of stronger social bonds on physiological stress increased both with increasing rates of aggression received and with decreasing minimum daily temperature. Ruling out thermoregulatory and immediate effects of social interactions on fGCM levels, our results indicate that male Barbary macaques employ a tend-and-befriend coping strategy in the face of increased environmental as well as social day-to-day stressors. This evidence of a stress-ameliorating effect of social bonding among males under natural conditions and beyond the mother–offspring, kin or pair bond broadens the generality of the social buffering hypothesis. PMID:25489097

  11. Rank-dependent grooming patterns and cortisol alleviation in Barbary macaques.

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    Sonnweber, Ruth S; Ravignani, Andrea; Stobbe, Nina; Schiestl, Gisela; Wallner, Bernard; Fitch, W Tecumseh

    2015-06-01

    Flexibly adapting social behavior to social and environmental challenges helps to alleviate glucocorticoid (GC) levels, which may have positive fitness implications for an individual. For primates, the predominant social behavior is grooming. Giving grooming to others is particularly efficient in terms of GC mitigation. However, grooming is confined by certain limitations such as time constraints or restricted access to other group members. For instance, dominance hierarchies may impact grooming partner availability in primate societies. Consequently specific grooming patterns emerge. In despotic species focusing grooming activity on preferred social partners significantly ameliorates GC levels in females of all ranks. In this study we investigated grooming patterns and GC management in Barbary macaques, a comparably relaxed species. We monitored changes in grooming behavior and cortisol (C) for females of different ranks. Our results show that the C-amelioration associated with different grooming patterns had a gradual connection with dominance hierarchy: while higher-ranking individuals showed lowest urinary C measures when they focused their grooming on selected partners within their social network, lower-ranking individuals expressed lowest C levels when dispersing their grooming activity evenly across their social partners. We argue that the relatively relaxed social style of Barbary macaque societies allows individuals to flexibly adapt grooming patterns, which is associated with rank-specific GC management. © 2015 Wiley Periodicals, Inc.

  12. Decoding Target Distance and Saccade Amplitude from Population Activity in the Macaque Lateral Intraparietal Area (LIP)

    Science.gov (United States)

    Bremmer, Frank; Kaminiarz, Andre; Klingenhoefer, Steffen; Churan, Jan

    2016-01-01

    Primates perform saccadic eye movements in order to bring the image of an interesting target onto the fovea. Compared to stationary targets, saccades toward moving targets are computationally more demanding since the oculomotor system must use speed and direction information about the target as well as knowledge about its own processing latency to program an adequate, predictive saccade vector. In monkeys, different brain regions have been implicated in the control of voluntary saccades, among them the lateral intraparietal area (LIP). Here we asked, if activity in area LIP reflects the distance between fovea and saccade target, or the amplitude of an upcoming saccade, or both. We recorded single unit activity in area LIP of two macaque monkeys. First, we determined for each neuron its preferred saccade direction. Then, monkeys performed visually guided saccades along the preferred direction toward either stationary or moving targets in pseudo-randomized order. LIP population activity allowed to decode both, the distance between fovea and saccade target as well as the size of an upcoming saccade. Previous work has shown comparable results for saccade direction (Graf and Andersen, 2014a,b). Hence, LIP population activity allows to predict any two-dimensional saccade vector. Functional equivalents of macaque area LIP have been identified in humans. Accordingly, our results provide further support for the concept of activity from area LIP as neural basis for the control of an oculomotor brain-machine interface. PMID:27630547

  13. Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques.

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    Katsuo Kimura

    Full Text Available In neurodegenerative disorders, such as Parkinson's disease (PD, alpha-synuclein (α-syn accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB. This α-syn-related pathology is termed synucleinopathy. It remains unclear how α-syn accumulation expands during the progress of synucleinopathy in the human brain. In our study, we investigated the patterns of distribution and propagation of forebrain neurons expressing α-syn in aged macaques. It was found that the occurrence of α-syn-positive neurons proceeded topologically based on the midbrain dopamine pathways arising from the substantia nigra and the ventral tegmental area where they were primarily observed. In the nigrostriatal or mesolimbic dopamine pathway, the age-dependent increase in α-syn-positive neurons was evident in the striatum or the nucleus accumbens, respectively. Concerning the nigrostriatal pathway, a mediolateral or rostrocaudal gradient was seen in the substantia nigra or the striatum, respectively, and a compensatory increase in dopamine transporter occurred in the striatum regardless of the decreased dopamine level. In the mesocortical dopamine pathway, α-syn-positive neurons appeared in the prefrontal and then motor areas of the frontal lobe. Given that neither LB formation nor clinical phenotype manifestation was detected in any of the monkeys examined in the present study, aged macaques may be useful as a potential presymptomatic model for PD and LB-related neuropsychiatric disorders.

  14. Acute traumatic spinal cord injury induces glial activation in the cynomolgus macaque (Macaca fascicularis).

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    Miller, A D; Westmoreland, S V; Evangelous, N R; Graham, A; Sledge, J; Nesathurai, S

    2012-06-01

    Traumatic spinal cord injury leads to direct myelin and axonal damage and leads to the recruitment of inflammatory cells to site of injury. Although rodent models have provided the greatest insight into the genesis of traumatic spinal cord injury (TSCI), recent studies have attempted to develop an appropriate non-human primate model. We explored TSCI in a cynomolgus macaque model using a balloon catheter to mimic external trauma to further evaluate the underlying mechanisms of acute TSCI. Following 1hour of spinal cord trauma, there were focal areas of hemorrhage and necrosis at the site of trauma. Additionally, there was a marked increased expression of macrophage-related protein 8, MMP9, IBA-1, and inducible nitric oxide synthase in macrophages and microglia at the site of injury. This data indicate that acute TSCI in the cynomolgus macaque is an appropriate model and that the earliest immunohistochemical changes noted are within macrophage and microglia populations. © 2012 John Wiley & Sons A/S.

  15. Pathogenicity Comparison Between the Kikwit and Makona Ebola Virus Variants in Rhesus Macaques.

    Science.gov (United States)

    Wong, Gary; Qiu, Xiangguo; de La Vega, Marc-Antoine; Fernando, Lisa; Wei, Haiyan; Bello, Alexander; Fausther-Bovendo, Hugues; Audet, Jonathan; Kroeker, Andrea; Kozak, Robert; Tran, Kaylie; He, Shihua; Tierney, Kevin; Soule, Geoff; Moffat, Estella; Günther, Stephan; Gao, George F; Strong, Jim; Embury-Hyatt, Carissa; Kobinger, Gary

    2016-10-15

    Enhanced virulence and/or transmission of West African Ebola virus (EBOV) variants, which are divergent from their Central African counterparts, are suspected to have contributed to the sizable toll of the recent Ebola virus disease (EVD) outbreak. This study evaluated the pathogenicity and shedding in rhesus macaques infected with 1 of 2 West African isolates (EBOV-C05 or EBOV-C07) or a Central African isolate (EBOV-K). All animals infected with EBOV-C05 or EBOV-C07 died of EVD, whereas 2 of 3 EBOV-K-infected animals died. The viremia level was elevated 10-fold in EBOV-C05-infected animals, compared with EBOV-C07- or EBOV-K-infected animals. More-severe lung pathology was observed in 2 of 6 EBOV-C05/C07-infected macaques. This is the first detailed analysis of the recently circulating EBOV-C05/C07 in direct compa