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Sample records for siv vaccine regimens

  1. Immunogenicity of viral vector, prime-boost SIV vaccine regimens in infant rhesus macaques: attenuated vesicular stomatitis virus (VSV) and modified vaccinia Ankara (MVA) recombinant SIV vaccines compared to live-attenuated SIV.

    Science.gov (United States)

    Van Rompay, Koen K A; Abel, Kristina; Earl, Patricia; Kozlowski, Pamela A; Easlick, Juliet; Moore, Joseph; Buonocore-Buzzelli, Linda; Schmidt, Kimberli A; Wilson, Robert L; Simon, Ian; Moss, Bernard; Rose, Nina; Rose, John; Marthas, Marta L

    2010-02-10

    In a previously developed infant macaque model mimicking HIV infection by breast-feeding, we demonstrated that intramuscular immunization with recombinant poxvirus vaccines expressing simian immunodeficiency virus (SIV) structural proteins provided partial protection against infection following oral inoculation with virulent SIV. In an attempt to further increase systemic but also local antiviral immune responses at the site of viral entry, we tested the immunogenicity of different orally administered, replicating vaccines. One group of newborn macaques received an oral prime immunization with a recombinant vesicular stomatitis virus expressing SIVmac239 gag, pol and env (VSV-SIVgpe), followed 2 weeks later by an intramuscular boost immunization with MVA-SIV. Another group received two immunizations with live-attenuated SIVmac1A11, administered each time both orally and intravenously. Control animals received mock immunizations or non-SIV VSV and MVA control vectors. Analysis of SIV-specific immune responses in blood and lymphoid tissues at 4 weeks of age demonstrated that both vaccine regimens induced systemic antibody responses and both systemic and local cell-mediated immune responses. The safety and immunogenicity of the VSV-SIVgpe+MVA-SIV immunization regimen described in this report provide the scientific incentive to explore the efficacy of this vaccine regimen against virulent SIV exposure in the infant macaque model. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  2. 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...

  3. Humoral immunity induced by mucosal and/or systemic SIV-specific vaccine platforms suggest novel combinatorial approaches for enhancing responses

    OpenAIRE

    Vargas-Inchaustegui, Diego A.; Tuero, Iskra; Mohanram, Venkatramanan; Musich, Thomas; Pegu, Poonam; Valentin, Antonio; Sui, Yongjun; Rosati, Margherita; Bear, Jenifer; Venzon, David J.; Kulkarni, Viraj; Alicea, Candido; Pilkington, Guy R.; Liyanage, Namal P.M.; Demberg, Thorsten

    2014-01-01

    Combinatorial HIV/SIV vaccine approaches targeting multiple arms of the immune system might improve protective efficacy. We compared SIV-specific humoral immunity induced in rhesus macaques by five vaccine regimens. Systemic regimens included ALVAC-SIVenv priming and Env boosting (ALVAC/Env); DNA immunization; and DNA plus Env co-immunization (DNA&Env). RepAd/Env combined mucosal replication-competent Ad-env priming with systemic Env boosting. A Peptide/Env regimen, given so...

  4. Comparison of protection from homologous cell-free vs cell-associated SIV challenge afforded by inactivated whole SIV vaccines.

    NARCIS (Netherlands)

    J.L. Heeney (Jonathan); P. de Vries (Petra); R. Dubbes (Rob); W. Koornstra (Willem); H. Niphuis; P. ten Haaft (Peter); J. Boes (Jolande); M.E.M. Dings (Marlinda); B. Morein (Bror); A.D.M.E. Osterhaus (Albert)

    1992-01-01

    textabstractThis study attempted to determine if SIV vaccines could protect against challenge with peripheral blood mononuclear cells (PBMCs) from an SIV infected rhesus monkey. Mature Macaca mulatta were vaccinated four times with formalin inactivated SIVmac32H administered in MDP adjuvant (n = 8)

  5. Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys.

    Science.gov (United States)

    Letvin, Norman L; Rao, Srinivas S; Montefiori, David C; Seaman, Michael S; Sun, Yue; Lim, So-Yon; Yeh, Wendy W; Asmal, Mohammed; Gelman, Rebecca S; Shen, Ling; Whitney, James B; Seoighe, Cathal; Lacerda, Miguel; Keating, Sheila; Norris, Philip J; Hudgens, Michael G; Gilbert, Peter B; Buzby, Adam P; Mach, Linh V; Zhang, Jinrong; Balachandran, Harikrishnan; Shaw, George M; Schmidt, Stephen D; Todd, John-Paul; Dodson, Alan; Mascola, John R; Nabel, Gary J

    2011-05-04

    The RV144 vaccine trial in Thailand demonstrated that an HIV vaccine could prevent infection in humans and highlights the importance of understanding protective immunity against HIV. We used a nonhuman primate model to define immune and genetic mechanisms of protection against mucosal infection by the simian immunodeficiency virus (SIV). A plasmid DNA prime/recombinant adenovirus serotype 5 (rAd5) boost vaccine regimen was evaluated for its ability to protect monkeys from infection by SIVmac251 or SIVsmE660 isolates after repeat intrarectal challenges. Although this prime-boost vaccine regimen failed to protect against SIVmac251 infection, 50% of vaccinated monkeys were protected from infection with SIVsmE660. Among SIVsmE660-infected animals, there was about a one-log reduction in peak plasma virus RNA in monkeys expressing the major histocompatibility complex class I allele Mamu-A*01, implicating cytotoxic T lymphocytes in the control of SIV replication once infection is established. Among Mamu-A*01-negative monkeys challenged with SIVsmE660, no CD8(+) T cell response or innate immune response was associated with protection against virus acquisition. However, low levels of neutralizing antibodies and an envelope-specific CD4(+) T cell response were associated with vaccine protection in these monkeys. Moreover, monkeys that expressed two TRIM5 alleles that restrict SIV replication were more likely to be protected from infection than monkeys that expressed at least one permissive TRIM5 allele. This study begins to elucidate the mechanisms of vaccine protection against immunodeficiency viruses and highlights the need to analyze these immune and genetic correlates of protection in future trials of HIV vaccine strategies.

  6. Protection of rhesus macaques from SIV infection by immunization with different experimental SIV vaccines.

    NARCIS (Netherlands)

    P. de Vries (Petra); J.L. Heeney (Jonathan); J. Boes (Jolande); M.E.M. Dings (Marlinda); E.G.J. Hulskotte (Ellen); R. Dubbes (Rob); W. Koornstra (Willem); P. ten Haaft (Peter); L. Akerblom; S. Eriksson (Sigrid); B. Morein (Bror); S. Norley (Steve); A.D.M.E. Osterhaus (Albert)

    1994-01-01

    textabstractThe immunogenicity and efficacy of an inactivated whole SIVmac (32H) preparation adjuvanted with muramyl dipeptide (SIV-MDP) and a gp120-enriched SIVmac (32H) ISCOM preparation (SIV-ISCOM), were compared by immunizing four rhesus macaques (Macaca mulatta) four times with SIV-MDP and four

  7. 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

  8. High-throughput profiling of anti-glycan humoral responses to SIV vaccination and challenge.

    Directory of Open Access Journals (Sweden)

    Christopher T Campbell

    Full Text Available Recent progress toward an HIV vaccine highlights both the potential of vaccines to end the AIDS pandemic and the need to boost efficacy by incorporating additional vaccine strategies. Although many aspects of the immune response can contribute to vaccine efficacy, the key factors have not been defined fully yet. A particular area that may yield new insights is anti-glycan immune responses, such as those against the glycan shield that HIV uses to evade the immune system. In this study, we used glycan microarray technology to evaluate anti-glycan antibody responses induced by SIV vaccination and infection in a non-human primate model of HIV infection. This comprehensive profiling of circulating anti-glycan antibodies found changes in anti-glycan antibody levels after both vaccination with the Ad5hr-SIV vaccine and SIV infection. Notably, SIV infection produced generalized declines in anti-glycan IgM antibodies in a number of animals. Additionally, some infected animals generated antibodies to the Tn antigen, which is a cryptic tumor-associated antigen exposed by premature termination of O-linked glycans; however, the Ad5hr-SIV vaccine did not induce anti-Tn IgG antibodies. Overall, this study demonstrates the potential contributions that glycan microarrays can make for HIV vaccine development.

  9. 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

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

    Directory of Open Access Journals (Sweden)

    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

  11. 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.

  12. CD40L-adjuvanted DNA/modified vaccinia virus Ankara simian immunodeficiency virus SIV239 vaccine enhances SIV-specific humoral and cellular immunity and improves protection against a heterologous SIVE660 mucosal challenge.

    Science.gov (United States)

    Kwa, Suefen; Lai, Lilin; Gangadhara, Sailaja; Siddiqui, Mariam; Pillai, Vinod B; Labranche, Celia; Yu, Tianwei; Moss, Bernard; Montefiori, David C; Robinson, Harriet L; Kozlowski, Pamela A; Amara, Rama Rao

    2014-09-01

    It remains a challenge to develop a successful human immunodeficiency virus (HIV) vaccine that is capable of preventing infection. Here, we utilized the benefits of CD40L, a costimulatory molecule that can stimulate both dendritic cells (DCs) and B cells, as an adjuvant for our simian immunodeficiency virus (SIV) DNA vaccine in rhesus macaques. We coexpressed the CD40L with our DNA/SIV vaccine such that the CD40L is anchored on the membrane of SIV virus-like particle (VLP). These CD40L containing SIV VLPs showed enhanced activation of DCs in vitro. We then tested the potential of DNA/SIV-CD40L vaccine to adjuvant the DNA prime of a DNA/modified vaccinia virus Ankara (MVA) vaccine in rhesus macaques. Our results demonstrated that the CD40L adjuvant enhanced the functional quality of anti-Env antibody response and breadth of anti-SIV CD8 and CD4 T cell responses, significantly delayed the acquisition of heterologous mucosal SIV infection, and improved viral control. Notably, the CD40L adjuvant enhanced the control of viral replication in the gut at the site of challenge that was associated with lower mucosal CD8 immune activation, one of the strong predictors of disease progression. Collectively, our results highlight the benefits of CD40L adjuvant for enhancing antiviral humoral and cellular immunity, leading to enhanced protection against a pathogenic SIV. A single adjuvant that enhances both humoral and cellular immunity is rare and thus underlines the importance and practicality of CD40L as an adjuvant for vaccines against infectious diseases, including HIV-1. Despite many advances in the field of AIDS research, an effective AIDS vaccine that can prevent infection remains elusive. CD40L is a key stimulator of dendritic cells and B cells and can therefore enhance T cell and antibody responses, but its overly potent nature can lead to adverse effects unless used in small doses. In order to modulate local expression of CD40L at relatively lower levels, we expressed

  13. Fragmentation of SIV-gag vaccine induces broader T cell responses.

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    Adel Benlahrech

    Full Text Available High mutation rates of human immunodeficiency virus (HIV allows escape from T cell recognition preventing development of effective T cell vaccines. Vaccines that induce diverse T cell immune responses would help overcome this problem. Using SIV gag as a model vaccine, we investigated two approaches to increase the breadth of the CD8 T cell response. Namely, fusion of vaccine genes to ubiquitin to target the proteasome and increase levels of MHC class I peptide complexes and gene fragmentation to overcome competition between epitopes for presentation and recognition.three vaccines were compared: full-length unmodified SIV-mac239 gag, full-length gag fused at the N-terminus to ubiquitin and 7 gag fragments of equal size spanning the whole of gag with ubiquitin-fused to the N-terminus of each fragment. Genes were cloned into a replication defective adenovirus vector and immunogenicity assessed in an in vitro human priming system. The breadth of the CD8 T cell response, defined by the number of distinct epitopes, was assessed by IFN-γ-ELISPOT and memory phenotype and cytokine production evaluated by flow cytometry. We observed an increase of two- to six-fold in the number of epitopes recognised in the ubiquitin-fused fragments compared to the ubiquitin-fused full-length gag. In contrast, although proteasomal targeting was achieved, there was a marked reduction in the number of epitopes recognised in the ubiquitin-fused full-length gag compared to the full-length unmodified gene, but there were no differences in the number of epitope responses induced by non-ubiquitinated full-length gag and the ubiquitin-fused mini genes. Fragmentation and ubiquitination did not affect T cell memory differentiation and polyfunctionality, though most responses were directed against the Ad5 vector.Fragmentation but not fusion with ubiquitin increases the breadth of the CD8 T vaccine response against SIV-mac239 gag. Thus gene fragmentation of HIV vaccines may maximise

  14. Estimating the impact of vaccination in acute SHIV-SIV infection

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    Ribeiro, Ruy [Los Alamos National Laboratory

    2008-01-01

    Human Immunodeficiency Virus (HIV) infects approxmately 0.5% of the world population, and is a major cause of morbidity and mortality worldwide. A vaccine for HIV is urgently required, and a variety of vaccine modalities have been tested in animal models of infection. A number of these studies have shown protection in monkey models of infection, although the ability of the vaccine to protect appears to vary with the viral strain and animal model used. The recent failure of a large vaccine study in humans suggests that further understanding of the basic dynamics of infection and impact of vaccination are required, in order to understand the variable efficacy of vaccination in different infections. The dynamics of HIV infection have been studied in humans and in a variety of animal models. The standard model of infection has been used to estimate the basic reproductive ratio (R{sub 0}) of the virus, calculated from the growth rate of virus in acute infection. This method has not been useful in studying the effects of vaccination, since, in the vaccines developed so far, early growth rates of virus do not differ between control and vaccinated animals. Here, we use the standard model of viral dynamics to derive the reproductive ratio from the peak viral load and nadir of target cell numbers in acute infection. We apply this method to data from studies of vaccination in Simian Human Immunodeficiency Virus (SHIV) and Simian Immunodeficiency Virus (SIV) infection and demonstrate that vaccination can reduce the reproductive ratio by 2.3 and 2 fold respectively. This method allows the comparison of vaccination efficacy amongst different viral strains and animal models in vivo.

  15. Live attenuated rubella vectors expressing SIV and HIV vaccine antigens replicate and elicit durable immune responses in rhesus macaques

    Science.gov (United States)

    2013-01-01

    Background Live attenuated viruses are among our most potent and effective vaccines. For human immunodeficiency virus, however, a live attenuated strain could present substantial safety concerns. We have used the live attenuated rubella vaccine strain RA27/3 as a vector to express SIV and HIV vaccine antigens because its safety and immunogenicity have been demonstrated in millions of children. One dose protects for life against rubella infection. In previous studies, rubella vectors replicated to high titers in cell culture while stably expressing SIV and HIV antigens. Their viability in vivo, however, as well as immunogenicity and antibody persistence, were unknown. Results This paper reports the first successful trial of rubella vectors in rhesus macaques, in combination with DNA vaccines in a prime and boost strategy. The vectors grew robustly in vivo, and the protein inserts were highly immunogenic. Antibody titers elicited by the SIV Gag vector were greater than or equal to those elicited by natural SIV infection. The antibodies were long lasting, and they were boosted by a second dose of replication-competent rubella vectors given six months later, indicating the induction of memory B cells. Conclusions Rubella vectors can serve as a vaccine platform for safe delivery and expression of SIV and HIV antigens. By presenting these antigens in the context of an acute infection, at a high level and for a prolonged duration, these vectors can stimulate a strong and persistent immune response, including maturation of memory B cells. Rhesus macaques will provide an ideal animal model for demonstrating immunogenicity of novel vectors and protection against SIV or SHIV challenge. PMID:24041113

  16. Vaccination and timing influence SIV immune escape viral dynamics in vivo.

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    Liyen Loh

    2008-01-01

    Full Text Available CD8+ cytotoxic T lymphocytes (CTL can be effective at controlling HIV-1 in humans and SIV in macaques, but their utility is partly offset by mutational escape. The kinetics of CTL escape and reversion of escape mutant viruses upon transmission to MHC-mismatched hosts can help us understand CTL-mediated viral control and the fitness cost extracted by immune escape mutation. Traditional methods for following CTL escape and reversion are, however, insensitive to minor viral quasispecies. We developed sensitive quantitative real-time PCR assays to track the viral load of SIV Gag164-172 KP9 wild-type (WT and escape mutant (EM variants in pigtail macaques. Rapid outgrowth of EM virus occurs during the first few weeks of infection. However, the rate of escape plateaued soon after, revealing a prolonged persistence of WT viremia not detectable by standard cloning and sequencing methods. The rate of escape of KP9 correlated with levels of vaccine-primed KP9-specific CD8+ T cells present at that time. Similarly, when non-KP9 responder (lacking the restricting Mane-A*10 allele macaques were infected with SHIVmn229 stock containing a mixture of EM and WT virus, rapid reversion to WT was observed over the first 2 weeks following infection. However, the rate of reversion to WT slowed dramatically over the first month of infection. The serial quantitation of escape mutant viruses evolving during SIV infection shows that rapid dynamics of immune escape and reversion can be observed in early infection, particularly when CD8 T cells are primed by vaccination. However, these early rapid rates of escape and reversion are transient and followed by a significant slowing in these rates later during infection, highlighting that the rate of escape is significantly influenced by the timing of its occurrence.

  17. Role of Occult and Post-acute Phase Replication in Protective Immunity Induced with a Novel Live Attenuated SIV Vaccine

    NARCIS (Netherlands)

    Berry, Neil; Manoussaka, Maria; Ham, Claire; Ferguson, Deborah; Tudor, Hannah; Mattiuzzo, Giada; Klaver, Bep; Page, Mark; Stebbings, Richard; Das, Atze T.; Berkhout, Ben; Almond, Neil; Cranage, Martin P.

    2016-01-01

    In order to evaluate the role of persisting virus replication during occult phase immunisation in the live attenuated SIV vaccine model, a novel SIVmac239Δnef variant (SIVrtTA) genetically engineered to replicate in the presence of doxycycline was evaluated for its ability to protect against

  18. 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.

  19. Comparative evaluation of oral and intranasal priming with replication-competent adenovirus 5 host range mutant (Ad5hr)-simian immunodeficiency virus (SIV) recombinant vaccines on immunogenicity and protective efficacy against SIV(mac251).

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    Zhou, Qifeng; Hidajat, Rachmat; Peng, Bo; Venzon, David; Aldrich, M Kristine; Richardson, Ersell; Lee, Eun Mi; Kalyanaraman, V S; Grimes, George; Gómez-Román, V Raúl; Summers, L Ebonita; Malkevich, Nina; Robert-Guroff, Marjorie

    2007-11-19

    Oral, replication-competent Ad-HIV vaccines are advancing to human trials. Previous evaluation of protective efficacy in non-human primates has primarily followed upper respiratory tract administrations. Here we compared sequential oral (O/O) versus intranasal/oral (I/O) priming of rhesus macaques with Ad5 host range mutant-SIV recombinants expressing SIV env/rev, gag, and nef genes followed by boosting with SIV gp120 protein. Cellular immune responses in PBMC were stronger and more frequent after I/O administration. Both groups developed mucosal immunity, including memory cells in bronchial alveolar lavage, and gut-homing receptors on PBMC. Following intrarectal SIV(mac251) challenge, both groups exhibited equivalent, significant protection and robust post-challenge cellular immunity. Our results illustrate the promise of oral replication-competent Ad-recombinant vaccines. Pre-challenge PBMC ELISPOT and proliferative responses did not predict protection in the O/O group, highlighting the need for simple, non-invasive methods to reliably assess mucosal immunity.

  20. HIV vaccine research and discovery in the nonhuman primates model: a unified theory in acquisition prevention and control of SIV infection.

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    Lynch, Rebecca M; Yamamoto, Takuya; McDermott, Adrian B

    2013-07-01

    Here we highlight the latest advances in HIV vaccine concepts that will expand our knowledge on how to elicit effective acquisition-prevention and/or control of simian immunodeficiency virus (SIV) replication in the nonhuman primate (NHP) model. In the context of the promising analyses from the RV144 Thai Trial and the effective control of SIV replication exerted by rhCMV-(SIV) elicited EM CD8 T cells, the HIV field has recently shifted toward vaccine concepts that combine protection from acquisition with effective control of SIV replication. Current studies in the NHP model have demonstrated the efficacy of HIV-neutralizing antibodies via passive transfer, the potential importance of the CD4 Tfh subset, the ability to effectively model the RV144 vaccine trial and the capacity of an Ad26 prime and modified vaccinia Ankara virus boost to elicit Env-specific antibody and cellular responses that both limit acquisition and control heterologous SIVmac251 challenge. The latest work in the NHP model suggests that the next generation HIV-1 vaccines should aim to provoke a comprehensive adaptive immune response for both prevention of SIV acquisition as well as control of replication in breakthrough infection.

  1. Intragastric administration of Lactobacillus plantarum and AT-2-inactivated SIV does not protect Indian rhesus macaques from intra-rectal SIV challenge nor reduce virus replication after transmission.

    Science.gov (United States)

    Carnathan, Diane G; Mackel, Joseph J; Sweat, Shelby L; Enemuo, Chiamaka A; Gebru, Etse H; Dhadvai, Pallavi; Gangadhara, Sailaja; Hicks, Sakeenah; Vanderford, Thomas H; Amara, Rama R; Esparza, José; Lu, Wei; Andrieu, Jean-Marie; Silvestri, Guido

    2018-02-28

    A major obstacle to development of an effective AIDS vaccine is that along with intended beneficial responses, immunization regimen may activate CD4+ T cells that can facilitate acquisition of HIV by serving as target cells for the virus. Lu et al. reported that intra-gastric administration of chemically inactivated SIV mac239 (iSIV) and Lactobacillus plantarum (LP) (iSIV+LP) protected 15/16 Chinese-origin rhesus macaques (RMs) from high-dose intra-rectal SIV mac239 challenge at three months post-immunization. They attributed the observed protection to induction of immune tolerance, mediated by "MHC-Ib/E-restricted CD8+ regulatory T cells that suppressed SIV-harboring CD4+ T cell activation and ex vivo SIV replication in 15/16 animals without inducing SIV-specific antibodies or cytotoxic T". Andrieu et al subsequently reported protection from infection in 23/24 RM immunized intragastrically or intravaginally with iSIV and BCG, LP or Lactobacillus rhamnosus , which they ascribed to the same tolerogenic mechanism. Using vaccine materials obtained from our co-authors, we conducted an immunization and challenge experiment in 54 Indian RMs, and included control groups receiving iSIV only or LP only, as well as unvaccinated animals. Intra-rectal challenge with SIV mac239 resulted in rapid infection in all groups of vaccinated RMs as well as unvaccinated controls. iSIV+LP vaccinated animals that became SIV infected showed viral loads similar to those observed in animals receiving iSIV only, LP only, and unvaccinated controls. The protection from SIV transmission conferred by intra-gastric iSIV+LP administration reported previously for Chinese origin RMs was not observed when the same experiment was conducted in a larger cohort of Indian-origin animals. IMPORTANCE: Despite increased understanding in immune responses against HIV, a safe and effective AIDS vaccine is not yet available. One obstacle is that immunization may activate CD4+ T cells that could act as target cells

  2. Enhanced expression of HIV and SIV vaccine antigens in the structural gene region of live attenuated rubella viral vectors and their incorporation into virions.

    Science.gov (United States)

    Virnik, Konstantin; Ni, Yisheng; Berkower, Ira

    2013-04-19

    Despite the urgent need for an HIV vaccine, its development has been hindered by virus variability, weak immunogenicity of conserved epitopes, and limited durability of the immune response. For other viruses, difficulties with immunogenicity were overcome by developing live attenuated vaccine strains. However, there is no reliable method of attenuation for HIV, and an attenuated strain would risk reversion to wild type. We have developed rubella viral vectors, based on the live attenuated vaccine strain RA27/3, which are capable of expressing important HIV and SIV vaccine antigens. The rubella vaccine strain has demonstrated safety, immunogenicity, and long lasting protection in millions of children. Rubella vectors combine the growth and immunogenicity of live rubella vaccine with the antigenicity of HIV or SIV inserts. This is the first report showing that live attenuated rubella vectors can stably express HIV and SIV vaccine antigens at an insertion site located within the structural gene region. Unlike the Not I site described previously, the new site accommodates a broader range of vaccine antigens without interfering with essential viral functions. In addition, antigens expressed at the structural site were controlled by the strong subgenomic promoter, resulting in higher levels and longer duration of antigen expression. The inserts were expressed as part of the structural polyprotein, processed to free antigen, and incorporated into rubella virions. The rubella vaccine strain readily infects rhesus macaques, and these animals will be the model of choice for testing vector growth in vivo and immunogenicity. Published by Elsevier Ltd.

  3. Membrane-bound SIV envelope trimers are immunogenic in ferrets after intranasal vaccination with a replication-competent canine distemper virus vector.

    Science.gov (United States)

    Zhang, Xinsheng; Wallace, Olivia; Wright, Kevin J; Backer, Martin; Coleman, John W; Koehnke, Rebecca; Frenk, Esther; Domi, Arban; Chiuchiolo, Maria J; DeStefano, Joanne; Narpala, Sandeep; Powell, Rebecca; Morrow, Gavin; Boggiano, Cesar; Zamb, Timothy J; Richter King, C; Parks, Christopher L

    2013-11-01

    We are investigating canine distemper virus (CDV) as a vaccine vector for the delivery of HIV envelope (Env) that closely resembles the native trimeric spike. We selected CDV because it will promote vaccine delivery to lymphoid tissues, and because human exposure is infrequent, reducing potential effects of pre-existing immunity. Using SIV Env as a model, we tested a number of vector and gene insert designs. Vectors containing a gene inserted between the CDV H and L genes, which encoded Env lacking most of its cytoplasmic tail, propagated efficiently in Vero cells, expressed the immunogen on the cell surface, and incorporated the SIV glycoprotein into progeny virus particles. When ferrets were vaccinated intranasally, there were no signs of distress, vector replication was observed in the gut-associated lymphoid tissues, and the animals produced anti-SIV Env antibodies. These data show that live CDV-SIV Env vectors can safely induce anti-Env immune responses following intranasal vaccination. © 2013 Elsevier Inc. All rights reserved.

  4. A peptide-loaded dendritic cell based cytotoxic T-lymphocyte (CTL vaccination strategy using peptides that span SIV Tat, Rev, and Env overlapping reading frames

    Directory of Open Access Journals (Sweden)

    Marx Preston A

    2006-01-01

    Full Text Available Abstract CTL based vaccine strategies in the macaque model of AIDS have shown promise in slowing the progression to disease. However, rapid CTL escape viruses can emerge rendering such vaccination useless. We hypothesized that such escape is made more difficult if the immunizing CTL epitope falls within a region of the virus that has a high density of overlapping reading frames which encode several viral proteins. To test this hypothesis, we immunized macaques using a peptide-loaded dendritic cell approach employing epitopes in the second coding exon of SIV Tat which spans reading frames for both Env and Rev. We report here that autologous dendritic cells, loaded with SIV peptides from Tat, Rev, and Env, induced a distinct cellular immune response measurable ex vivo. However, conclusive in vivo control of a challenge inoculation of SIVmac239 was not observed suggesting that CTL epitopes within densely overlapping reading frames are also subject to escape mutations.

  5. Fewer Doses of HPV Vaccine Result in Immune Response Similar to Three-Dose Regimen

    Science.gov (United States)

    ... Note Fewer doses of HPV vaccine result in immune response similar to three-dose regimen Posted: November 4, ... or three doses of Cervarix. They also measured immune responses of unvaccinated women who, at enrollment, were found ...

  6. Increases in NKG2C Expression on T Cells and Higher Levels of Circulating CD8+B Cells Are Associated with Sterilizing Immunity Provided by a Live Attenuated SIV Vaccine.

    Science.gov (United States)

    Hodara, Vida L; Parodi, Laura M; Keckler, M Shannon; Giavedoni, Luis D

    Vaccines based on live attenuated viruses are highly effective immunogens in the simian immunodeficiency virus (SIV)/rhesus macaque animal model and offer the possibility of studying correlates of protection against infection with virulent virus. We utilized a tether system for studying, in naive macaques and animals vaccinated with a live-attenuated vaccine, the acute events after challenge with pathogenic SIV. This approach allowed for the frequent sampling of small blood volumes without sedation or restraining of the animals, thus reducing the confounding effect of sampling stress. Before challenge, vaccinated animals presented significantly higher levels of proliferating and activated B cells than naive macaques, which were manifested by high expression of CD8 on B cells. After SIV challenge, the only changes observed in protected vaccinated macaques were significant increases in expression of the NK marker NKG2C on CD4 and CD8 T cells. We also identified that infection of naive macaques with SIV resulted in a transient peak of expression of CD20 on CD8 T cells and a constant rise in the number of B cells expressing CD8. Finally, analysis of a larger cohort of vaccinated animals identified that, even when circulating levels of vaccine virus are below the limit of detection, live attenuated vaccines induce systemic increases of IP-10 and perforin. These studies indicate that components of both the innate and adaptive immune systems of animals inoculated with a live-attenuated SIV vaccine respond to and control infection with virulent virus. Persistence of the vaccine virus in tissues may explain the elevated cytokine and B-cell activation levels. In addition, our report underpins the utility of the tether system for the intensive study of acute immune responses to viral infections.

  7. Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects.

    Science.gov (United States)

    Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

    2017-06-03

    To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China.

  8. Increased T cell breadth and antibody response elicited in prime-boost regimen by viral vector encoded homologous SIV Gag/Env in outbred CD1 mice

    DEFF Research Database (Denmark)

    Andersson, Anne Marie Carola; Holst, Peter Johannes

    2016-01-01

    ) or homologous (SIVmac239) gag sequences using adenovirus (Ad5) and MVA vectors. Env (SIVmac239) was co-encoded in the vectors to study the induction of antibodies, which is a primary target of current HIV vaccine designs. All three vaccines were designed as virus-encoded virus-like particle vaccines. Antibody...

  9. IL-2, IL-7 and IL-15 as immuno-modulators during SIV/HIV vaccination and treatment.

    Science.gov (United States)

    Leone, Amanda; Picker, Louis J; Sodora, Donald L

    2009-01-01

    While highly active antiretroviral therapy (HAART) regimens have proven to be effective in controlling active HIV replication, complete recovery of CD4+ T cells does not always occur, even among patients with high level virologic control. Recent advances in understanding the biology of T cell production and homeostasis have created the potential to augment anti-viral therapies with immunotherapies designed to facilitate recovery of the HIV-damaged immune system, in particular, the recovery of CD4+ T cell populations. The common gamma-chain cytokines IL-2, IL-7 and IL-15 are primary regulators of T cell homeostasis and thus have been considered prime candidate immunotherapeutics, both for increasing T cell levels/function and for augmenting vaccine-elicited viral-specific T cell responses. Recent studies have established that these cytokines have distinct functional roles in immune homeostasis, which focus on specific T cell populations. The ability of these cytokines to provide immunotherapeutic benefit to HIV+ patients will depend on their ability to stably increase or functionally enhance the desired T cell target population without adverse virologic or clinical consequences.

  10. Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen

    Science.gov (United States)

    Mealey, Robert H.; Leib, Steven R.; Littke, Matt H.; Wagner, Bettina; Horohov, David W.; McGuire, Travis C.

    2009-01-01

    Effective DNA-based vaccines against lentiviruses will likely induce CTL against conserved viral proteins. Equine infectious anemia virus (EIAV) infects horses worldwide, and serves as a useful model for lentiviral immune control. Although attenuated live EIAV vaccines have induced protective immune responses, DNA-based vaccines have not. In particular, DNA-based vaccines have had limited success in inducing CTL responses against intracellular pathogens in the horse. We hypothesized that priming with a codon-optimized plasmid encoding EIAV Gag p15/p26 with co-administration of a plasmid encoding an equine IL-2/IgG fusion protein as a molecular adjuvant, followed by boosting with a vaccinia vector expressing Gag p15/p26, would induce protective Gag-specific CTL responses. Although the regimen induced Gag-specific CTL in four of seven vaccinated horses, CTL were not detected until after the vaccinia boost, and protective effects were not observed in EIAV challenged vaccinates. Unexpectedly, vaccinates had significantly higher viral loads and more severe clinical disease, associated with the presence of vaccine-induced CTL. It was concluded that 1.) further optimization of the timing and route of DNA immunization was needed for efficient CTL priming in vivo, 2.) co-administration of the IL-2/IgG plasmid did not enhance CTL priming by the Gag p15/p26 plasmid, 3.) vaccinia vectors are useful for lentivirus-specific CTL induction in the horse, 4.) Gag-specific CTL alone are either insufficient or a more robust Gag-specific CTL response is needed to limit EIAV viremia and clinical disease, and 5.) CTL-inducing vaccines lacking envelope immunogens can result in lentiviral disease enhancement. Although the mechanisms for enhancement associated with this vaccine regimen remain to be elucidated, these results have important implications for development of lentivirus T cell vaccines. PMID:19368787

  11. Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials

    Directory of Open Access Journals (Sweden)

    Julia L. Hurwitz

    2010-02-01

    Full Text Available Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans.

  12. A Simplified 4-Site Economical Intradermal Post-Exposure Rabies Vaccine Regimen: A Randomised Controlled Comparison with Standard Methods

    Science.gov (United States)

    Warrell, Mary J.; Riddell, Anna; Yu, Ly-Mee; Phipps, Judith; Diggle, Linda; Bourhy, Hervé; Deeks, Jonathan J.; Fooks, Anthony R.; Audry, Laurent; Brookes, Sharon M.; Meslin, François-Xavier; Moxon, Richard; Pollard, Andrew J.; Warrell, David A.

    2008-01-01

    Background The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods. Methods Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available. Findings All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method. Conclusions This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be

  13. A simplified 4-site economical intradermal post-exposure rabies vaccine regimen: a randomised controlled comparison with standard methods.

    Directory of Open Access Journals (Sweden)

    Mary J Warrell

    2008-04-01

    Full Text Available The need for economical rabies post-exposure prophylaxis (PEP is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods.Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90; or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available.All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method.This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be introduced without further

  14. A randomized open-labeled study to demonstrate the non-inferiority of purified chick-embryo cell rabies vaccine administered in the Zagreb regimen (2-1-1) compared with the Essen regimen in Chinese adults.

    Science.gov (United States)

    Ma, Jingchen; Wang, Hongchang; Li, Jun; Chang, Likuan; Xie, Yun; Liu, Zhonglin; Zhao, Yuliang; Malerczyk, Claudius; Claudius, Malerczyk

    2014-01-01

    The Zagreb regimen has been used for 20 years in various countries. In China, until 2010, the Zagreb schedule was only approved for purified chick embryo cell vaccine (PCECV) and purified Vero cell rabies vaccines (PVRV). In this phase III clinical trial, we aimed to demonstrate the safety and immunogenic non-inferiority of the Zagreb regimen compared with the Essen regimen in healthy adult Chinese immunized with PCECV (Rabipur®). The study enrolled 825 subjects aged 18 to 50 years; serum samples were collected on Days 0, 7, 14, 42, and at 13 months to assess rabies virus neutralizing antibody (RVNA) concentrations. Solicited and unsolicited local and systemic reactions were recorded for 6 days following the day of vaccination, and collected throughout the entire study period (Day 1 until Month 13). The Zagreb regimen was non-inferior to the Essen regimen with regard to RVNA concentrations after 7, 14, and 42 days, and 13 months of immunization. The non-inferiority of seroconversion was established at Days 14 and 42. The incidence of local and systemic reactions was similar between groups, and mostly of mild or moderate severity. Vaccine-related adverse events occurred more frequently in the Essen group than in the Zagreb group. Vaccination with PCECV under a 2-1-1 regimen is as safe and immunogenic as under the traditional 5-dose Essen regimen for rabies post-exposure prophylaxis, and is a more cost-effective option, has a more practical vaccination schedule, and can potentially increase compliance.

  15. Conditionally-live attenuated SIV upregulates global T effector memory cell frequency under replication permissive conditions

    NARCIS (Netherlands)

    Manoussaka, Maria S.; Berry, Neil; Ferguson, Deborah; Stebbings, Richard; Robinson, Mark; Ham, Claire; Page, Mark; Li, Bo; Das, Atze T.; Berkhout, Ben; Almond, Neil; Cranage, Martin P.

    2013-01-01

    Live attenuated SIV induces potent protection against superinfection with virulent virus; however the mechanism of this vaccine effect is poorly understood. Such knowledge is important for the development of clinically acceptable vaccine modalities against HIV. Using a novel, doxycycline dependent,

  16. 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.

  17. Conserved molecular signatures in gp120 are associated with the genetic bottleneck during simian immunodeficiency virus (SIV), SIV-human immunodeficiency virus (SHIV), and HIV type 1 (HIV-1) transmission.

    Science.gov (United States)

    Gonzalez, Mileidy W; DeVico, Anthony L; Lewis, George K; Spouge, John L

    2015-04-01

    Human immunodeficiency virus (HIV) transmission typically results from infection by a single transmitted/founder (T/F) variant. Are T/F variants chosen uniformly at random from the donor pool, or are they selected based on advantageous traits facilitating transmission? Finding evidence for selection during transmission is of particular interest, because it would indicate that phenotypic and/or genetic properties of the viruses might be harnessed as potential vaccine targets or immunotherapies. Here, we systematically evaluated the differences between the Env proteins of simian immunodeficiency virus/simian HIV (SIV/SHIV) stock and T/F variants in search of "signature" sites of transmission. We also surveyed residue preferences in HIV at the SIV/SHIV signature sites. Four sites of gp120 showed significant selection, and an additional two sites showed a similar trend. Therefore, the six sites clearly differentiate T/F viruses from the majority of circulating variants in the stocks. The selection of SIV/SHIV could be inferred reasonably across both vaccinated and unvaccinated subjects, with infections resulting from vaginal, rectal, and intravenous routes of transmission and regardless of viral dosage. The evidence for selection in SIV and SHIV T/F variants is strong and plentiful, and in HIV the evidence is suggestive though commensurate with the availability of suitable data for analysis. Two of the signature residues are completely conserved across the SIV, SHIV, and HIV variants we examined. Five of the signature residues map to the C1 region of gp120 and one to the signal peptide. Our data raise the possibility that C1, while governing the association between gp120 and gp41, modulates transmission efficiency, replicative fitness, and/or host cell tropism at the level of virus-cell attachment and entry. The present study finds significant evidence of selection on gp120 molecules of SIV/SHIV T/F viruses. The data provide ancillary evidence suggesting the same sites

  18. Is an HIV vaccine possible?

    Directory of Open Access Journals (Sweden)

    Nancy A. Wilson

    Full Text Available The road to the discovery of a vaccine for HIV has been arduous and will continue to be difficult over the ensuing twenty years. Most vaccines are developed by inducing neutralizing antibodies against the target pathogen or by using attenuated strains of the particular pathogen to engender a variety of protective immune responses. Unfortunately, simple methods of generating anti-HIV antibodies have already failed in a phase III clinical trial. While attenuated SIV variants work well against homologous challenges in non-human primates, the potential for reversion to a more pathogenic virus and recombination with challenge viruses will preclude the use of attenuated HIV in the field. It has been exceedingly frustrating to vaccinate for HIV-specific neutralizing antibodies given the enormous diversity of the Envelope (Env glycoprotein and its well-developed glycan shield. However, there are several antibodies that will neutralize many different strains of HIV and inducing these types of antibodies in vaccinees remains the goal of a vigorous effort to develop a vaccine for HIV based on neutralizing antibodies. Given the difficulty in generating broadly reactive neutralizing antibodies, the HIV vaccine field has turned its attention to inducing T cell responses against the virus using a variety of vectors. Unfortunately, the results from Merck's phase IIb STEP trial proved to be disappointing. Vaccinees received Adenovirus type 5 (Ad5 expressing Gag, Pol, and Nef of HIV. This vaccine regimen failed to either prevent infection or reduce the level of HIV replication after challenge. These results mirrored those in non-human primate testing of Ad5 using rigorous SIV challenge models. This review will focus on recent developments in HIV vaccine development. We will deal largely with attempts to develop a T cell-based vaccine using the non-human primate SIV challenge model.

  19. Short-Term Immunogenicity and Safety of an Accelerated Pre-Exposure Prophylaxis Regimen With Japanese Encephalitis Vaccine in Combination With a Rabies Vaccine: A Phase III, Multicenter, Observer-Blind Study.

    Science.gov (United States)

    Jelinek, Tomas; Burchard, Gerd D; Dieckmann, Sebastian; Bühler, Silja; Paulke-Korinek, Maria; Nothdurft, Hans D; Reisinger, Emil; Ahmed, Khaleel; Bosse, Dietrich; Meyer, Seetha; Costantini, Marco; Pellegrini, Michele

    2015-01-01

    The current Japanese encephalitis (JE) vaccination regimen requires two doses and 4 weeks to complete, which may not always be feasible for travelers on short notice. One of the primary endpoints of this phase III study was to demonstrate noninferiority of immune responses to a JE vaccine following an accelerated 1-week JE vaccination regimen administered concomitantly with a rabies vaccine as compared to a standard 4-week JE regimen alone. In addition, the immunogenicity of concomitant administration of JE and rabies vaccines following standard regimens was evaluated, as well as the tolerability and safety profile of each regimen under study. Healthy adults aged 18 to ≤65 years were randomized to regimens with an accelerated or standard schedule: JE+rabies-standard (n = 167), JE+rabies-accelerated (n = 217) or JE-standard (n = 56). Immunogenicity against JE antigen was assessed by a 50% plaque reduction neutralization test (PRNT50 ) titer of ≥1 : 10, measured 28 days after last active vaccine (LAV) administration. Solicited reactions were collected 7 days after each vaccination; spontaneously reported adverse events (AEs) and serious AEs were monitored up to day 57. This paper reports results until day 57. Noninferiority of immune responses was established for JE+rabies-accelerated compared to the JE-standard regimen 28 days after LAV administration. Overall, 99% and 100% of subjects in the JE+rabies-accelerated and JE-standard groups, respectively, achieved PRNT50 titers of ≥1 : 10 at 28 days after LAV administration. No impact of concomitant rabies vaccination was observed either on immune responses or on the safety profile of the JE vaccine. This was the first randomized, controlled trial that demonstrated the strong short-term immunogenicity of a new, accelerated, 1-week JE-regimen, which was noninferior to that of the standard regimen, with a satisfactory tolerability and safety profile and no impact of concomitant rabies vaccination. This accelerated

  20. A heterologous prime-boost Ebola virus vaccine regimen induces durable neutralizing antibody response and prevents Ebola virus-like particle entry in mice.

    Science.gov (United States)

    Chen, Tan; Li, Dapeng; Song, Yufeng; Yang, Xi; Liu, Qingwei; Jin, Xia; Zhou, Dongming; Huang, Zhong

    2017-09-01

    Ebola virus (EBOV) is one of the most virulent pathogens known to humans. Neutralizing antibodies play a major role in the protection against EBOV infections. Thus, an EBOV vaccine capable of inducing a long-lasting neutralizing antibody response is highly desirable. We report here that a heterologous prime-boost vaccine regimen can elicit durable EBOV-neutralizing antibody response in mice. A chimpanzee serotype 7 adenovirus expressing EBOV GP (denoted AdC7-GP) was generated and used for priming. A truncated version of EBOV GP1 protein (denoted GP1t) was produced at high levels in Drosophila S2 cells and used for boosting. Mouse immunization studies showed that the AdC7-GP prime/GP1t boost vaccine regimen was more potent in eliciting neutralizing antibodies than either the AdC7-GP or GP1t alone. Neutralizing antibodies induced by the heterologous prime-boost regimen sustained at high titers for at least 18 weeks after immunization. Significantly, in vivo challenge studies revealed that the entry of reporter EBOV-like particles was efficiently blocked in mice receiving the heterologous prime-boost regimen even at 18 weeks after the final dose of immunization. These results suggest that this novel AdC7-GP prime/GP1t boost regimen represents an EBOV vaccine approach capable of establishing long-term protection, and therefore warrants further development. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. SIV Infection of Lung Macrophages.

    Directory of Open Access Journals (Sweden)

    Yue Li

    Full Text Available HIV-1 depletes CD4+ T cells in the blood, lymphatic tissues, gut and lungs. Here we investigated the relationship between depletion and infection of CD4+ T cells in the lung parenchyma. The lungs of 38 Indian rhesus macaques in early to later stages of SIVmac251 infection were examined, and the numbers of CD4+ T cells and macrophages plus the frequency of SIV RNA+ cells were quantified. We showed that SIV infected macrophages in the lung parenchyma, but only in small numbers except in the setting of interstitial inflammation where large numbers of SIV RNA+ macrophages were detected. However, even in this setting, the number of macrophages was not decreased. By contrast, there were few infected CD4+ T cells in lung parenchyma, but CD4+ T cells were nonetheless depleted by unknown mechanisms. The CD4+ T cells in lung parenchyma were depleted even though they were not productively infected, whereas SIV can infect large numbers of macrophages in the setting of interstitial inflammation without depleting them. These observations point to the need for future investigations into mechanisms of CD4+ T cell depletion at this mucosal site, and into mechanisms by which macrophage populations are maintained despite high levels of infection. The large numbers of SIV RNA+ macrophages in lungs in the setting of interstitial inflammation indicates that lung macrophages can be an important source for SIV persistent infection.

  2. Antibody titers in animal bite victims after post exposure vaccination with intradermally administered purified vero cell rabies vaccine using modified thai red cross regimen

    International Nuclear Information System (INIS)

    Hafeez, S.; Tahir, Z.

    2014-01-01

    To determine the seroconversion following rabies vaccination by intradermal route in cases of animal bite attending Anti rabies center, Lahore for post exposure prophylaxis. Study Design: Cross sectional descriptive study. Place and Duration: Antirabies center, Birdwood road Lahore, Microbiology laboratory, office of Bacteriologist, Government of Punjab, Lahore. Patients and Methods: Victims of all ages and both sexes having exposure with suspected rabid animal within 24 - 72 hours were included, fulfilling inclusion and exclusion criteria, over 3 months period from February to April 20. Patients of Category II and III wounds were included. Purified vero cell vaccine (PVR V) with antigenic content> 2.5 ml was used for intradermal vaccination according to modified Thai Red Cross regimen (2-2-2-0-2). Each victim received 0.1 ml intradermal dose on each deltoid on day 0, 3, 7 and 28th day of bite. Blood samples from victims were taken on day 0, 14 and 35. Antibody titers were estimated by ELISA kit. Results: Fifty cases were studied including 20 children. Male female ratio was 4:1. Optimum serocon version (> 0.5 IU/ml) was achieved in all cases by day 14. Antibody levels increased further (> 4 IV/ml) in 92% cases on day 35. Geometric mean titers were 3.2 IU/ml and 6.2 IU/ml on day 14 and 35 respectively. Conclusion: Intradermal route for cell culture rabies vaccine for postexposure prophylaxis in animal bite victims was efficacious and safe. The smaller dosage of vaccine was economically affordable by patients in referral centers. (author)

  3. The potential of the CMB305 vaccine regimen to target NY-ESO-1 and improve outcomes for synovial sarcoma and myxoid/round cell liposarcoma patients.

    Science.gov (United States)

    Pollack, Seth M

    2018-02-01

    Synovial Sarcoma (SS) and Myxoid Round Cell Liposarcoma (MRCL) are devastating sarcoma subtypes with few treatment options and poor outcomes in the advanced setting. However, both these diseases may be ideal for novel immunotherapies targeting the cancer-testis antigen, NY-ESO-1. Areas covered: In this review, we discuss the novel NY-ESO-1 targeted vaccine regimen, CMB305. This regimen uses a unique integration-deficient, dendritic-cell targeting lentiviral vector from the ZVex® platform, LV305, in order to prime NY-ESO-1 specific T cells. LV305 has single agent activity, and, in one case, caused a durable partial response in a refractory SS patient. CMB305 also includes a boost from a NY-ESO-1 protein vaccine given along with a potent toll-like-4 receptor agonist, glycopyranosyl lipid A. CMB305 induces NY-ESO-1 specific T cell responses in both SS and MRC patients and these patients had excellent overall survival (OS) outcomes in the initial phase I study. Expert commentary: CMB305 is a therapeutic vaccine regimen targeting NY-ESO-1 based on the lentiviral vaccine vector, LV305. Phase I studies have proven this vaccine is active immunologically. Data suggesting this vaccine may improve OS for SS and MRCL patients is exciting but early, and on-going work is testing the impact of CMB305 on patient outcomes.

  4. A two-dose heterologous prime-boost vaccine regimen eliciting sustained immune responses to Ebola Zaire could support a preventive strategy for future outbreaks.

    Science.gov (United States)

    Shukarev, Georgi; Callendret, Benoit; Luhn, Kerstin; Douoguih, Macaya

    2017-02-01

    The consequences of the 2013-16 Ebola Zaire virus disease epidemic in West Africa were grave. The economies, healthcare systems and communities of Guinea, Sierra Leone and Liberia were devastated by over 18 months of active Ebola virus transmission, followed by sporadic resurgences potentially related to sexual transmission by survivors with viral persistence in body fluids following recovery. The need to develop and implement strategies to prevent and mitigate future outbreaks is now beyond dispute. The potential for unpredictable outbreaks of indeterminate duration, and control challenges posed by the possibility of sporadic re-emergence, mean that implementation of an effective vaccination program for outbreak containment necessitates a vaccine providing durable immunity. Heterologous prime-boost vaccine regimens deliver the same or similar antigens through different vaccine types, the first to prime and the second to boost the immune system. Ad26.ZEBOV/MVA-BN-Filo is an investigational Ebola Zaire vaccine regimen that uses this heterologous prime-boost approach. Preliminary Phase 1 data suggest that Ad26.ZEBOV/MVA-BN-Filo confers durable immunity for at least 240 d and is well-tolerated with a good safety profile. This regimen may therefore be suitable for prophylactic use in a regional or targeted population vaccination strategy, and could potentially aid prevention and control of future Ebola outbreaks.

  5. Modified vaccinia virus ankara recombinants are as potent as vaccinia recombinants in diversified prime and boost vaccine regimens to elicit therapeutic antitumor responses.

    Science.gov (United States)

    Hodge, James W; Poole, Diane J; Aarts, Wilhelmina M; Gómez Yafal, Alicia; Gritz, Linda; Schlom, Jeffrey

    2003-11-15

    Cancer vaccine regimens use various strategies to enhance immune responses to specific tumor-associated antigens (TAAs), including the increasing use of recombinant poxviruses [vaccinia (rV) and fowlpox (rF)] for delivery of the TAA to the immune system. However, the use of replication competent vectors with the potential of adverse reactions have made attenuation a priority for next-generation vaccine strategies. Modified vaccinia Ankara (MVA) is a replication defective form of vaccinia virus. Here, we investigated the use of MVA encoding a tumor antigen gene, carcinoembryonic antigen (CEA), in addition to multiple costimulatory molecules (B7-1, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3 designated TRICOM). Vaccination of mice with MVA-CEA/TRICOM induced potent CD4+ and CD8+ T-cell responses specific for CEA. MVA-CEA/TRICOM could be administered twice in vaccinia naïve mice and only a single time in vaccinia-immune mice before being inhibited by antivector-immune responses. The use of MVA-CEA/TRICOM in a diversified prime and boost vaccine regimen with rF-CEA/TRICOM, however, induced significantly greater levels of both CD4+ and CD8+ T-cell responses specific for CEA than that seen with rV-CEA/TRICOM prime and rF-CEA/TRICOM boost. In a self-antigen tumor model, the diversified MVA-CEA/TRICOM/rF-CEA/ TRICOM vaccination regimen resulted in a significant therapeutic antitumor response as measured by increased survival, when compared with the diversified prime and boost regimen, rV-CEA/TRICOM/rF-CEA/TRICOM. The studies reported here demonstrate that MVA, when used as a prime in a diversified vaccination, is clearly comparable with the regimen using the recombinant vaccinia in both the induction of cellular immune responses specific for the "self"-TAA transgene and in antitumor activity.

  6. Traveling waves for two SIV models

    Directory of Open Access Journals (Sweden)

    REN Jingli

    2015-06-01

    Full Text Available The existence of traveling waves is established for a diffusive SIV system with constant total population. The approach used is the geometric singular perturbation method. The same result is suitable to another SIV system with exponential input.

  7. Zika Virus: Immune Evasion Mechanisms, Currently Available Therapeutic Regimens, and Vaccines.

    Science.gov (United States)

    Asif, Arun; Manzoor, Sobia; Tuz-Zahra, Fatima; Saalim, Muhammad; Ashraf, Maliha; Ishtiyaq, Javeria; Khalid, Madiha

    2017-12-01

    The sudden emergence of infectious pathogens such as Zika virus (ZIKV) holds global health concerns. Recent dissemination of ZIKV from Pacific to Americas with an upsurge of congenital anomalies and Guillain Barre Syndrome (GBS) in adults has created an alarming situation. High-throughput studies are in progress to understand ZIKV's mode of pathogenesis and mechanism of immune escape, yet the pathogenesis remains obscure. Mainly ZIKV's envelope (E) protein and nonstructural proteins (mainly NS1 and NS5) manipulate host cell to support viral immune escape by modulation of the interferon pathway and complement antagonism. The development of direct therapeutics for ZIKV infection is required to overcome the rapidly evolving viral threat. Currently, the existing strategies for ZIKV treatment are only supportive. Although, there is no prophylactic or therapeutic vaccine presently available, however, recent efforts have brought up ZIKV vaccines into clinical trial phase 1. This review presents the highlights of recent advances in understanding immune evasion strategies adapted by ZIKV and existing therapies against the virus.

  8. Conditionally replicating HIV and SIV variants

    NARCIS (Netherlands)

    Das, Atze T.; Berkhout, Ben

    2016-01-01

    Conditionally replicating human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) variants that can be switched on and off at will are attractive tools for HIV and SIV research. We constructed HIV and SIV variants in which the natural transcription control mechanism was replaced

  9. Non-clinical efficacy and safety of HyVac4:IC31 vaccine administered in a BCG prime-boost regimen.

    Science.gov (United States)

    Skeiky, Yasir A W; Dietrich, Jes; Lasco, Todd M; Stagliano, Katherine; Dheenadhayalan, Veerabadran; Goetz, Margaret Ann; Cantarero, Luis; Basaraba, Randall J; Bang, Peter; Kromann, Ingrid; McMclain, J Bruce; Sadoff, Jerald C; Andersen, Peter

    2010-01-22

    Despite the extensive success with the introduction of M. bovis Bacille Calmette-Guérin (BCG), tuberculosis (TB) remains a major global epidemic infecting between 8 and 9 million people annually with an estimated 1.7 million deaths each year. However, because of its demonstrated effectiveness against some of the most severe forms of childhood TB, it is now realized that BCG vaccination of newborns is unlikely to be replaced. Therefore, BCG or an improved BCG will continue to be used as a prime TB vaccine and there is a need to develop effective boost vaccines that would enhance and prolong the protective immunity induced by BCG prime immunization. We report on a heterologous booster approach using two highly immunogenic TB antigens comprising Ag85B and TB10.4 (HyVac4) delivered as a fusion molecule and formulated in the proprietary adjuvant IC31. This vaccine was found to be immunogenic and demonstrated greater protection in the more stringent guinea pig model of pulmonary tuberculosis than BCG alone when used in a prime/boost regimen. Significant difference in lung involvement was observed for all animals in the HyVac4 boosted group compared to BCG alone regardless of time to death or sacrifice. A vaccine toxicology study of the HyVac4:IC31 regimen was performed and it was judged safe to advance the vaccine into clinical trials. Therefore, all non-clinical data supports the suitability of HyVac4 as a safe, immunogenic, and effective vaccination in a prime-boost regimen with BCG.

  10. Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions

    International Nuclear Information System (INIS)

    Devitt, Gerard; Emerson, Vanessa; Holtkotte, Denise; Pfeiffer, Tanya; Pisch, Thorsten; Bosch, Valerie

    2007-01-01

    Low level incorporation of the viral glycoprotein (Env) into human immunodeficiency virus (HIV) particles is a major drawback for vaccine strategies against HIV/AIDS in which HIV particles are used as immunogen. Within this study, we have examined two strategies aimed at achieving higher levels of Env incorporation into non-infectious pseudovirions (PVs). First, we have generated chimeric HIV/SIV Env proteins containing the truncated C-terminal tail region of simian immunodeficiency virus (SIV)mac239-Env767 stop , which mediates strongly increased incorporation of SIV-Env into SIV particles. In a second strategy, we have employed a truncated HIV-Env protein (Env-Tr752 N750K ) which we have previously demonstrated to be incorporated into HIV virions, generated in infected T-cells, to a higher level than that of Wt-HIV-Env. Although the chimeric HIV/SIV Env proteins were expressed at the cell surface and induced increased levels of cell-cell fusion in comparison to Wt-HIV-Env, they did not exhibit increased incorporation into either HIV-PVs or SIV-PVs. Only Env-Tr752 N750K exhibited significantly higher (threefold) levels of incorporation into HIV-PVs, an improvement, which, although not dramatic, is worthwhile for the large-scale preparation of non-infectious PVs for vaccine studies aimed at inducing Env humoral responses

  11. Immunotherapy of Congenital SIV Infection.

    Science.gov (United States)

    1996-10-01

    Yudi n Hs these infants do not die of opportunistic with nef-deleted SIV (18). Tl.d, all adult Robert A. Rasmussen infections in our biocontainment... Zhang YJ, Putkonen P, Albert J, et al.: Stable biological and anti- genic characteristics of HIV-2sBt" 69 in nonpathogenic infection of macaques

  12. A Phase 1 Human Immunodeficiency Virus Vaccine Trial for Cross-Profiling the Kinetics of Serum and Mucosal Antibody Responses to CN54gp140 Modulated by Two Homologous Prime-Boost Vaccine Regimens

    Directory of Open Access Journals (Sweden)

    Sven Kratochvil

    2017-05-01

    Full Text Available A key aspect to finding an efficacious human immunodeficiency virus (HIV vaccine is the optimization of vaccine schedules that can mediate the efficient maturation of protective immune responses. In the present study, we investigated the effect of alternate booster regimens on the immune responses to a candidate HIV-1 clade C CN54gp140 envelope protein, which was coadministered with the TLR4-agonist glucopyranosyl lipid A-aqueous formulation. Twelve study participants received a common three-dose intramuscular priming series followed by a final booster at either 6 or 12 months. The two homologous prime-boost regimens were well tolerated and induced CN54gp140-specific responses that were observed in both the systemic and mucosal compartments. Levels of vaccine-induced IgG-subclass antibodies correlated significantly with FcγR engagement, and both vaccine regimens were associated with strikingly similar patterns in antibody titer and FcγR-binding profiles. In both groups, identical changes in the antigen (Ag-specific IgG-subclass fingerprint, leading to a decrease in IgG1 and an increase in IgG4 levels, were modulated by booster injections. Here, the dissection of immune profiles further supports the notion that prime-boost strategies are essential for the induction of diverse Ag-specific HIV-1 responses. The results reported here clearly demonstrate that identical responses were effectively and safely induced by both vaccine regimens, indicating that an accelerated 6-month regimen could be employed for the rapid induction of immune responses against CN54gp140 with no apparent impact on the overall quality of the induced immune response. (This study has been registered at http://ClinicalTrials.gov under registration no. NCT01966900.

  13. Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP.

    Science.gov (United States)

    Rampling, Tommy; Ewer, Katie J; Bowyer, Georgina; Bliss, Carly M; Edwards, Nick J; Wright, Danny; Payne, Ruth O; Venkatraman, Navin; de Barra, Eoghan; Snudden, Claudia M; Poulton, Ian D; de Graaf, Hans; Sukhtankar, Priya; Roberts, Rachel; Ivinson, Karen; Weltzin, Rich; Rajkumar, Bebi-Yassin; Wille-Reece, Ulrike; Lee, Cynthia K; Ockenhouse, Christian F; Sinden, Robert E; Gerry, Stephen; Lawrie, Alison M; Vekemans, Johan; Morelle, Danielle; Lievens, Marc; Ballou, Ripley W; Cooke, Graham S; Faust, Saul N; Gilbert, Sarah; Hill, Adrian V S

    2016-09-01

    The need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (RTS,S/AS01B) and the other inducing potent T-cell responses to thrombospondin-related adhesion protein (TRAP) by using a viral vector. Thirty-seven healthy malaria-naive adults were vaccinated with either a chimpanzee adenovirus 63 and modified vaccinia virus Ankara-vectored vaccine expressing a multiepitope string fused to TRAP and 3 doses of RTS,S/AS01B (group 1; n = 20) or 3 doses of RTS,S/AS01B alone (group 2; n = 17). CHMI was delivered by mosquito bites to 33 vaccinated subjects at week 12 after the first vaccination and to 6 unvaccinated controls. No suspected unexpected serious adverse reactions or severe adverse events related to vaccination were reported. Protective vaccine efficacy was observed in 14 of 17 subjects (82.4%) in group 1 and 12 of 16 subjects (75%) in group 2. All control subjects received a diagnosis of blood-stage malaria parasite infection. Both vaccination regimens were immunogenic. Fourteen protected subjects underwent repeat CHMI 6 months after initial CHMI; 7 of 8 (87.5%) in group 1 and 5 of 6 (83.3%) in group 2 remained protected. The high level of sterile efficacy observed in this trial is encouraging for further evaluation of combination approaches using these vaccine types. NCT01883609. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  14. Evaluation of a vaccination regimen and care in relation to follow-up and treatment of patients with inflammatory bowel disease.

    Science.gov (United States)

    Yamamoto-Furusho, J K; Sarmiento-Aguilar, A; Parra-Holguín, N N; Bozada-Gutiérrez, K E

    2018-03-28

    During the clinical course of inflammatory bowel disease, different causes can compromise kidney, liver, and bone marrow function and increase the risk for osteoporosis, infections, and neoplasias. The aim of the present study was to describe the follow-up of Mexican patients with inflammatory bowel disease in relation to their vaccination regimen, treatment-associated risks, and cancer screening. A retrospective cross-sectional study was conducted within the time frame of February and June 2017. One hundred patients that had a histopathologic diagnosis of inflammatory bowel disease were surveyed about their follow-up vaccination regimen, treatment-associated risks, and cancer screening. SPSS v24 software was employed for the statistical analysis. One hundred patients with inflammatory bowel disease were studied (90% with ulcerative colitis and 10% with Crohn's disease; 60% women, 40% men): 75% stated that they had no vaccination regimen. A total of 71.4% of the women had at least one Pap smear in their lives and 28.6% did not have them done annually. Twenty-four percent of the patients wore sun block daily. A total of 18.2% of the patients with more than a 10-year progression of ulcerative colitis had an annual colonoscopy. Yearly kidney function was registered in 57.1% of the patients, 92.9% had a yearly complete blood count, and 78.6% had yearly liver function tests. A total of 34.8% of patients had no bone densitometry in their case records. These results are a red flag suggesting the need to reinforce the role of the primary healthcare providers in relation to vaccination follow-up and the need to improve the education of the patient in relation to inflammatory bowel disease. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  15. Cytotoxic Capacity of SIV-Specific CD8+ T Cells against Primary Autologous Targets Correlates with Immune Control in SIV-Infected Rhesus Macaques

    Science.gov (United States)

    Mendoza, Daniel; Migueles, Stephen A.; Rood, Julia E.; Peterson, Bennett; Johnson, Sarah; Doria-Rose, Nicole; Schneider, Douglas; Rakasz, Eva; Trivett, Matthew T.; Trubey, Charles M.; Coalter, Vicky; Hallahan, Claire W.; Watkins, David; Franchini, Genoveffa; Lifson, Jeffrey D.; Connors, Mark

    2013-01-01

    Although the study of non-human primates has resulted in important advances for understanding HIV-specific immunity, a clear correlate of immune control over simian immunodeficiency virus (SIV) replication has not been found to date. In this study, CD8+ T-cell cytotoxic capacity was examined to determine whether this function is a correlate of immune control in the rhesus macaque (RM) SIV infection model as has been suggested in chronic HIV infection. SIVmac251-infected human reverse transcriptase (hTERT)-transduced CD4+ T-cell clone targets were co-incubated with autologous macaque effector cells to measure infected CD4+ T-cell elimination (ICE). Twenty-three SIV-infected rhesus macaques with widely varying plasma viral RNA levels were evaluated in a blinded fashion. Nineteen of 23 subjects (83%) were correctly classified as long-term nonprogressor/elite controller (LTNP/EC), slow progressor, progressor or SIV-negative rhesus macaques based on measurements of ICE (weighted Kappa 0.75). LTNP/EC had higher median ICE than progressors (67.3% [22.0–91.7%] vs. 23.7% [0.0–58.0%], p = 0.002). In addition, significant correlations between ICE and viral load (r = −0.57, p = 0.01), and between granzyme B delivery and ICE (r = 0.89, pspecific CD8+ T cells and efficient delivery of active granzyme B to SIV-infected targets are associated with superior control of SIV infection in rhesus macaques, consistent with observations of HIV infection in humans. Therefore, such measurements appear to represent a correlate of control of viral replication in chronic SIV infection and their role as predictors of immunologic control in the vaccine setting should be evaluated. PMID:23468632

  16. A prime-boost immunization regimen based on a simian adenovirus 36 vectored multi-stage malaria vaccine induces protective immunity in mice.

    Science.gov (United States)

    Fonseca, Jairo A; McCaffery, Jessica N; Kashentseva, Elena; Singh, Balwan; Dmitriev, Igor P; Curiel, David T; Moreno, Alberto

    2017-05-31

    Malaria remains a considerable burden on public health. In 2015, the WHO estimates there were 212 million malaria cases causing nearly 429,000 deaths globally. A highly effective malaria vaccine is needed to reduce the burden of this disease. We have developed an experimental vaccine candidate (PyCMP) based on pre-erythrocytic (CSP) and erythrocytic (MSP1) stage antigens derived from the rodent malaria parasite P. yoelii. Our protein-based vaccine construct induces protective antibodies and CD4 + T cell responses. Based on evidence that viral vectors increase CD8 + T cell-mediated immunity, we also have tested heterologous prime-boost immunization regimens that included human adenovirus serotype 5 vector (Ad5), obtaining protective CD8 + T cell responses. While Ad5 is commonly used for vaccine studies, the high prevalence of pre-existing immunity to Ad5 severely compromises its utility. Here, we report the use of the novel simian adenovirus 36 (SAd36) as a candidate for a vectored malaria vaccine since this virus is not known to infect humans, and it is not neutralized by anti-Ad5 antibodies. Our study shows that the recombinant SAd36PyCMP can enhance specific CD8 + T cell response and elicit similar antibody titers when compared to an immunization regimen including the recombinant Ad5PyCMP. The robust immune responses induced by SAd36PyCMP are translated into a lower parasite load following P. yoelii infectious challenge when compared to mice immunized with Ad5PyCMP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Dynamics of immune escape during HIV/SIV infection.

    Directory of Open Access Journals (Sweden)

    Christian L Althaus

    Full Text Available Several studies have shown that cytotoxic T lymphocytes (CTLs play an important role in controlling HIV/SIV infection. Notably, the observation of escape mutants suggests a selective pressure induced by the CTL response. However, it remains difficult to assess the definite role of the cellular immune response. We devise a computational model of HIV/SIV infection having a broad cellular immune response targeting different viral epitopes. The CTL clones are stimulated by viral antigen and interact with the virus population through cytotoxic killing of infected cells. Consequently, the virus population reacts through the acquisition of CTL escape mutations. Our model provides realistic virus dynamics and describes several experimental observations. We postulate that inter-clonal competition and immunodominance may be critical factors determining the sequential emergence of escapes. We show that even though the total killing induced by the CTL response can be high, escape rates against a single CTL clone are often slow and difficult to estimate from infrequent sequence measurements. Finally, our simulations show that a higher degree of immunodominance leads to more frequent escape with a reduced control of viral replication but a substantially impaired replicative capacity of the virus. This result suggests two strategies for vaccine design: Vaccines inducing a broad CTL response should decrease the viral load, whereas vaccines stimulating a narrow but dominant CTL response are likely to induce escape but may dramatically reduce the replicative capacity of the virus.

  18. Hepatitis B Vaccination Induced TNF-α- and IL-2-Producing T Cell Responses in HIV− Healthy Individuals Higher than in HIV+ Individuals Who Received the Same Vaccination Regimen

    Directory of Open Access Journals (Sweden)

    Kriangkrai Chawansuntati

    2018-01-01

    Full Text Available We investigated cytokine production and expression of degranulation marker CD107a after different strategies of hepatitis B virus (HBV vaccination in human immunodeficiency virus-infected individuals, which were three doses of 20 μg (standard dose group, four doses of 20 μg (four doses group, or four doses of 40 μg (four double doses group, compared to standard dose vaccination in healthy controls. PBMCs collected at different time points were stimulated in vitro with recombinant hepatitis B surface antigen and analyzed by flow cytometry. There was an increase in TNF-α production of total and memory CD4+ T cells at 7 months after vaccination in healthy controls compared to the HIV+ group, which received the same standard vaccination regimen. An increase in the IL-2-producing memory CD4+ T cells in the healthy control group was also observed at 7 months after vaccination. No differences were observed between the healthy controls and both groups of four doses at any time point of study. These results suggest that the standard HBV vaccination schedule might induce better production of TNF-α and IL-2 from CD4+ T cells in healthy individuals. Modification of HBV vaccination schedule by increasing the frequency and/or dosage may improve the CMI response in HIV-infected individuals. This trial is registered with NCT1289106.

  19. Peptide Based Vaccine Approaches for Cancer—A Novel Approach Using a WT-1 Synthetic Long Peptide and the IRX-2 Immunomodulatory Regimen

    Directory of Open Access Journals (Sweden)

    James E. Egan

    2011-10-01

    Full Text Available Therapeutic cancer vaccines have the potential to generate a long lasting immune response that will destroy tumor cells with specificity and safety, in contrast to many other current cancer therapies. Clinical success to date has been limited by a number of factors including choice of immunogenic cancer rejection antigens, optimization of vaccine platforms and immune adjuvants to effectively polarize the immune response, and incorporation of strategies to reverse cancer mediated immune suppression by utilization of effective adjuvant/immune modulators. WT-1 (Wilms’ tumor gene 1 is a cancer antigen that is required for tumorigenesis, expressed in a high percentage of tumor cells and rarely expressed in adult normal cells. Moreover spontaneous immunity to WT-1 is seen in cancer patients and can be augmented with various therapeutic vaccine approaches. IRX-2 is an immune modulator with demonstrated preclinical and clinical pleiotropic immune activities including enhancement of the immune response to potential tumor antigens. This paper presents the rationale and preclinical data for utilizing the WT-1 tumor antigen in a novel vaccine platform consisting of a synthetic long peptide containing multiple class I and class II epitopes in combination with the IRX-2 immunomodulatory regimen to overcome immuno-suppressive pathways and enhance the anti-tumor response.

  20. Peptide Based Vaccine Approaches for Cancer—A Novel Approach Using a WT-1 Synthetic Long Peptide and the IRX-2 Immunomodulatory Regimen

    Energy Technology Data Exchange (ETDEWEB)

    Naylor, Paul H.; Egan, James E.; Berinstein, Neil L., E-mail: nberinstein@irxtherapeutics.com [IRX Therapeutics, 140 W 57th Street, New York, NY 10019 (United States)

    2011-10-25

    Therapeutic cancer vaccines have the potential to generate a long lasting immune response that will destroy tumor cells with specificity and safety, in contrast to many other current cancer therapies. Clinical success to date has been limited by a number of factors including choice of immunogenic cancer rejection antigens, optimization of vaccine platforms and immune adjuvants to effectively polarize the immune response, and incorporation of strategies to reverse cancer mediated immune suppression by utilization of effective adjuvant/immune modulators. WT-1 (Wilms' tumor gene 1) is a cancer antigen that is required for tumorigenesis, expressed in a high percentage of tumor cells and rarely expressed in adult normal cells. Moreover spontaneous immunity to WT-1 is seen in cancer patients and can be augmented with various therapeutic vaccine approaches. IRX-2 is an immune modulator with demonstrated preclinical and clinical pleiotropic immune activities including enhancement of the immune response to potential tumor antigens. This paper presents the rationale and preclinical data for utilizing the WT-1 tumor antigen in a novel vaccine platform consisting of a synthetic long peptide containing multiple class I and class II epitopes in combination with the IRX-2 immunomodulatory regimen to overcome immuno-suppressive pathways and enhance the anti-tumor response.

  1. 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.

  2. Immunogenicity of heterologous recombinant adenovirus prime-boost vaccine regimens is enhanced by circumventing vector cross-reactivity

    NARCIS (Netherlands)

    Thorner, Anna R.; Lemckert, Angelique A. C.; Goudsmit, Jaap; Lynch, Diana M.; Ewald, Bonnie A.; Denholtz, Matthew; Havenga, Menzo J. E.; Barouch, Dan H.

    2006-01-01

    The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations has led to the development of recombinant adenovirus (rAd) vectors derived from rare Ad serotypes as vaccine candidates for human immunodeficiency virus type 1 and other pathogens. Vaccine vectors have

  3. 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.

  4. Efficacy of a single-dose regimen of inactivated whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial.

    Science.gov (United States)

    Qadri, Firdausi; Ali, Mohammad; Lynch, Julia; Chowdhury, Fahima; Khan, Ashraful Islam; Wierzba, Thomas F; Excler, Jean-Louis; Saha, Amit; Islam, Md Taufiqul; Begum, Yasmin A; Bhuiyan, Taufiqur R; Khanam, Farhana; Chowdhury, Mohiul I; Khan, Iqbal Ansary; Kabir, Alamgir; Riaz, Baizid Khoorshid; Akter, Afroza; Khan, Arifuzzaman; Asaduzzaman, Muhammad; Kim, Deok Ryun; Siddik, Ashraf U; Saha, Nirod C; Cravioto, Alejandro; Singh, Ajit P; Clemens, John D

    2018-03-14

    A single-dose regimen of inactivated whole-cell oral cholera vaccine (OCV) is attractive because it reduces logistical challenges for vaccination and could enable more people to be vaccinated. Previously, we reported the efficacy of a single dose of an OCV vaccine during the 6 months following dosing. Herein, we report the results of 2 years of follow-up. In this placebo-controlled, double-blind trial done in Dhaka, Bangladesh, individuals aged 1 year or older with no history of receipt of OCV were randomly assigned to receive a single dose of inactivated OCV or oral placebo. The primary endpoint was a confirmed episode of non-bloody diarrhoea for which the onset was at least 7 days after dosing and a faecal culture was positive for Vibrio cholerae O1 or O139. Passive surveillance for diarrhoea was done in 13 hospitals or major clinics located in or near the study area for 2 years after the last administered dose. We assessed the protective efficacy of the OCV against culture-confirmed cholera occurring 7-730 days after dosing with both crude and multivariable per-protocol analyses. This trial is registered at ClinicalTrials.gov, number NCT02027207. Between Jan 10, 2014, and Feb 4, 2014, 205 513 people were randomly assigned to receive either vaccine or placebo, of whom 204 700 (102 552 vaccine recipients and 102 148 placebo recipients) were included in the per-protocol analysis. 287 first episodes of cholera (109 among vaccine recipients and 178 among placebo recipients) were detected during the 2-year follow-up; 138 of these episodes (46 in vaccine recipients and 92 in placebo recipients) were associated with severe dehydration. The overall incidence rates of initial cholera episodes were 0·22 (95% CI 0·18 to 0·27) per 100 000 person-days in vaccine recipients versus 0·36 (0·31 to 0·42) per 100 000 person-days in placebo recipients (adjusted protective efficacy 39%, 95% CI 23 to 52). The overall incidence of severe cholera was 0·09 (0·07 to 0

  5. Natural SIV hosts: showing AIDS the door.

    Science.gov (United States)

    Chahroudi, Ann; Bosinger, Steven E; Vanderford, Thomas H; Paiardini, Mirko; Silvestri, Guido

    2012-03-09

    Many species of African nonhuman primates are naturally infected with simian immunodeficiency viruses (SIVs) in the wild and in captivity. In contrast to HIV-infected humans, these natural SIV hosts typically do not develop AIDS, despite chronic infection with a highly replicating virus. In this Review, we discuss the most recent advances on the mechanisms of protection from disease progression in natural SIV hosts, with emphasis on how they differ from pathogenic HIV/SIV infections of humans and rhesus macaques. These mechanisms include: (i) resolution of immune activation after acute infection, (ii) restricted pattern of target cell infection, and (iii) protection from mother-to-infant transmission. We highlight the areas that should be pursued in future studies, focusing on potential applications for the treatment and prevention of HIV infection.

  6. Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine

    Science.gov (United States)

    Hellerstein, Michael; Xu, Yongxian; Marino, Tracie; Lu, Shan; Yi, Hong; Wright, Elizabeth R.; Robinson, Harriet L.

    2012-01-01

    Here, we report on GEO-D03, a DNA vaccine that co-expresses non-infectious HIV-1 virus-like particles (VLPs) and the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). The virus-like particles display the native gp160 form of the HIV-1 Envelope glycoprotein (Env) and are designed to elicit antibody against the natural form of Env on virus and virus-infected cells. The DNA-expressed HIV Gag, Pol and Env proteins also have the potential to elicit virus-specific CD4 and CD8 T cells. The purpose of the co-expressed GM-CSF is to target a cytokine that recruits, expands and differentiates macrophages and dendritic cells to the site of VLP expression. The GEO-D03 DNA vaccine is currently entered into human trials as a prime for a recombinant modified vaccinia Ankara (MVA) boost. In preclinical studies in macaques using an SIV prototype vaccine, this vaccination regimen elicited both anti-viral T cells and antibody, and provided 70% protection against acquisition during 12 weekly rectal exposures with a heterologous SIV. Higher avidity of the Env-specific Ab for the native form of the Env in the challenge virus correlated with lower likelihood of SIV infection. PMID:23111169

  7. Preferential Targeting of Conserved Gag Regions after Vaccination with a Heterologous DNA Prime-Modified Vaccinia Virus Ankara Boost HIV-1 Vaccine Regimen.

    Science.gov (United States)

    Bauer, Asli; Podola, Lilli; Mann, Philipp; Missanga, Marco; Haule, Antelmo; Sudi, Lwitiho; Nilsson, Charlotta; Kaluwa, Bahati; Lueer, Cornelia; Mwakatima, Maria; Munseri, Patricia J; Maboko, Leonard; Robb, Merlin L; Tovanabutra, Sodsai; Kijak, Gustavo; Marovich, Mary; McCormack, Sheena; Joseph, Sarah; Lyamuya, Eligius; Wahren, Britta; Sandström, Eric; Biberfeld, Gunnel; Hoelscher, Michael; Bakari, Muhammad; Kroidl, Arne; Geldmacher, Christof

    2017-09-15

    Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function, and specificity of Gag-specific T cells induced by a DNA-prime modified vaccinia virus Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding a subtype B and AB-recombinant Gag p37 and two vaccinations with MVA-CMDR encoding subtype A Gag p55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells. After the first MVA-CMDR boost, vaccine-induced gamma interferon-positive (IFN-γ + ) Gag-specific T-cell responses were dominated by CD4 + T cells ( P viruses. While including multiple variants for a given immunogen in prime-boost vaccination strategies is one approach that aims to improve coverage for global virus variants, the immunologic consequences of this strategy have been poorly defined so far. It is unclear whether inclusion of multiple variants in prime-boost vaccination strategies improves recognition of variant viruses by T cells and by which mechanisms this would be achieved, either by improved cross-recognition of multiple variants for a given antigenic region or through preferential targeting of antigenic regions more conserved between prime and boost. Engineering vaccines to induce adaptive immune responses that preferentially target conserved antigenic regions of viral vulnerability might facilitate better immune control after preventive and therapeutic vaccination for HIV and for other variable viruses. Copyright © 2017 American Society for Microbiology.

  8. 'Omics investigations of HIV and SIV pathogenesis and innate immunity.

    Science.gov (United States)

    Palermo, Robert E; Fuller, Deborah H

    2013-01-01

    In the 30 years since the advent of the AIDS epidemic, the biomedical community has put forward a battery of molecular therapies that are based on the accumulated knowledge of a limited number of viral targets. Despite these accomplishments, the community still confronts unanswered foundational questions about HIV infection. What are the cellular or biomolecular processes behind HIV pathogenesis? Can we elucidate the characteristics that distinguish those individuals who are naturally resistant to either infection or disease progression? The discovery of simian immunodeficiency viruses (SIVs) and the ensuing development of in vivo, nonhuman primate (NHP) infection models was a tremendous advance, especially in abetting the exploration of vaccine strategies. And while there have been numerous NHP infection models and vaccine trials performed, fundamental questions remain regarding host-virus interactions and immune correlates of protection. These issues are, perhaps, most starkly illustrated with the appreciation that many species of African nonhuman primates are naturally infected with strains of SIV that do not cause any appreciable disease while replicating to viral loads that match or exceed those seen with pathogenic SIV infections in Asian species of nonhuman primates. The last decade has seen the establishment of high-throughput molecular profiling tools, such as microarrays for transcriptomics, SNP arrays for genome features, and LC-MS techniques for proteins or metabolites. These provide the capacity to interrogate a biological model at a comprehensive, systems level, in contrast to historical approaches that characterized a few genes or proteins in an experiment. These methods have already had revolutionary impacts in understanding human diseases originating within the host genome such as genetic disorders and cancer, and the methods are finding increasing application in the context of infectious disease. We will provide a review of the use of such 'omics

  9. Evaluation of in vitro cross-reactivity to avian H5N1 and pandemic H1N1 2009 influenza following prime boost regimens of seasonal influenza vaccination in healthy human subjects: a randomised trial.

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    Delia Bethell

    Full Text Available INTRODUCTION: Recent studies have demonstrated that inactivated seasonal influenza vaccines (IIV may elicit production of heterosubtypic antibodies, which can neutralize avian H5N1 virus in a small proportion of subjects. We hypothesized that prime boost regimens of live and inactivated trivalent seasonal influenza vaccines (LAIV and IIV would enhance production of heterosubtypic immunity and provide evidence of cross-protection against other influenza viruses. METHODS: In an open-label study, 26 adult volunteers were randomized to receive one of four vaccine regimens containing two doses of 2009-10 seasonal influenza vaccines administered 8 (±1 weeks apart: 2 doses of LAIV; 2 doses of IIV; LAIV then IIV; IIV then LAIV. Humoral immunity assays for avian H5N1, 2009 pandemic H1N1 (pH1N1, and seasonal vaccine strains were performed on blood collected pre-vaccine and 2 and 4 weeks later. The percentage of cytokine-producing T-cells was compared with baseline 14 days after each dose. RESULTS: Subjects receiving IIV had prompt serological responses to vaccine strains. Two subjects receiving heterologous prime boost regimens had enhanced haemagglutination inhibition (HI and neutralization (NT titres against pH1N1, and one subject against avian H5N1; all three had pre-existing cross-reactive antibodies detected at baseline. Significantly elevated titres to H5N1 and pH1N1 by neuraminidase inhibition (NI assay were observed following LAIV-IIV administration. Both vaccines elicited cross-reactive CD4+ T-cell responses to nucleoprotein of avian H5N1 and pH1N1. All regimens were safe and well tolerated. CONCLUSION: Neither homologous nor heterologous prime boost immunization enhanced serum HI and NT titres to 2009 pH1N1 or avian H5N1 compared to single dose vaccine. However heterologous prime-boost vaccination did lead to in vitro evidence of cross-reactivity by NI; the significance of this finding is unclear. These data support the strategy of

  10. Stability of the Gorilla Microbiome Despite SIV Infection

    OpenAIRE

    Moeller, Andrew H.; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H.; Ochman, Howard

    2015-01-01

    Simian Immunodeficiency Viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in fecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. He...

  11. Human immunodeficiency virus: scientific challenges impeding candidate vaccines.

    Science.gov (United States)

    Idemyor, Vincent

    2003-01-01

    Most initial work with HIV vaccines was directed at developing vaccines that elicited neutralizing antibodies. These neutralizing antibodies have been narrow in the focus of their action and specific almost entirely to the strain of the innoculating virus. Additionally, controversy has been reported about both the design of assay systems to measure the neutralization of such isolates and interpretation of the results. Researchers are now looking for a "broad-spectrum" vaccine; however, the high variability of the HIV envelope glycoprotein and its rapid rate of mutation creates an elusive target. Safety concerns have reduced interest in live attenuated virus or whole killed virus vaccines. Some novel approaches being taken include increasing cytotoxic T-lymphocyte responses, induction of immune responses in mucosal tissue surfaces, peptide-based vaccines, oligomeric envelope protein-based vaccine regimens, recombinant Tat protein vaccines, natural killer T-cell (NKT) ligand serving as adjuvant, and fusion of SIV gag with the extracellular domain of CTLA-4 as adjuvant. Most of the HIV vaccines currently in development are the products of recombinant DNA technology.

  12. Simple Mathematical Models Do Not Accurately Predict Early SIV Dynamics

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    Cecilia Noecker

    2015-03-01

    Full Text Available Upon infection of a new host, human immunodeficiency virus (HIV replicates in the mucosal tissues and is generally undetectable in circulation for 1–2 weeks post-infection. Several interventions against HIV including vaccines and antiretroviral prophylaxis target virus replication at this earliest stage of infection. Mathematical models have been used to understand how HIV spreads from mucosal tissues systemically and what impact vaccination and/or antiretroviral prophylaxis has on viral eradication. Because predictions of such models have been rarely compared to experimental data, it remains unclear which processes included in these models are critical for predicting early HIV dynamics. Here we modified the “standard” mathematical model of HIV infection to include two populations of infected cells: cells that are actively producing the virus and cells that are transitioning into virus production mode. We evaluated the effects of several poorly known parameters on infection outcomes in this model and compared model predictions to experimental data on infection of non-human primates with variable doses of simian immunodifficiency virus (SIV. First, we found that the mode of virus production by infected cells (budding vs. bursting has a minimal impact on the early virus dynamics for a wide range of model parameters, as long as the parameters are constrained to provide the observed rate of SIV load increase in the blood of infected animals. Interestingly and in contrast with previous results, we found that the bursting mode of virus production generally results in a higher probability of viral extinction than the budding mode of virus production. Second, this mathematical model was not able to accurately describe the change in experimentally determined probability of host infection with increasing viral doses. Third and finally, the model was also unable to accurately explain the decline in the time to virus detection with increasing viral

  13. Efficacy of different DNA and MVA prime-boost vaccination regimens against a Rift Valley fever virus (RVFV) challenge in sheep 12 weeks following vaccination.

    Science.gov (United States)

    Lorenzo, Gema; López-Gil, Elena; Ortego, Javier; Brun, Alejandro

    2018-02-21

    The aim of this work was to evaluate the immunogenicity and efficacy of DNA and MVA vaccines encoding the RVFV glycoproteins Gn and Gc in an ovine model of RVFV infection. Adult sheep of both sexes were challenged 12 weeks after the last immunization and clinical, virological, biochemical and immunological consequences, were analyzed. Strategies based on immunization with homologous DNA or heterologous DNA/MVA prime-boost were able to induce a rapid in vitro neutralizing antibody response as well as IFNγ production after in vitro virus specific re-stimulation. In these animals we observed reduced viremia levels and less clinical signs when compared with mock-immunized controls. In contrast, sheep inoculated with a homologous MVA prime-boost showed increased viremia correlating with the absence of detectable neutralizing antibody responses, despite of inducing cellular responses after the last immunization. However, faster induction of neutralizing antibodies and IFNγ production after challenge were found in this group when compared to the mock vaccinated group, indicative of a primed immune response. In conclusion, these results suggest that vaccination strategies based on DNA priming were able to mount and maintain specific anti-RVFV glycoprotein immune responses upon homologous or heterologous booster doses, warranting further optimization in large animal models of infection.

  14. A Plasmodium vivax Plasmid DNA- and Adenovirus-Vectored Malaria Vaccine Encoding Blood-Stage Antigens AMA1 and MSP142in a Prime/Boost Heterologous Immunization Regimen Partially Protects Aotus Monkeys against Blood-Stage Challenge.

    Science.gov (United States)

    Obaldia, Nicanor; Stockelman, Michael G; Otero, William; Cockrill, Jennifer A; Ganeshan, Harini; Abot, Esteban N; Zhang, Jianfeng; Limbach, Keith; Charoenvit, Yupin; Doolan, Denise L; Tang, De-Chu C; Richie, Thomas L

    2017-04-01

    Malaria is caused by parasites of the genus Plasmodium , which are transmitted to humans by the bites of Anopheles mosquitoes. After the elimination of Plasmodium falciparum , it is predicted that Plasmodium vivax will remain an important cause of morbidity and mortality outside Africa, stressing the importance of developing a vaccine against P. vivax malaria. In this study, we assessed the immunogenicity and protective efficacy of two P. vivax antigens, apical membrane antigen 1 (AMA1) and the 42-kDa C-terminal fragment of merozoite surface protein 1 (MSP1 42 ) in a plasmid recombinant DNA prime/adenoviral (Ad) vector boost regimen in Aotus monkeys. Groups of 4 to 5 monkeys were immunized with plasmid DNA alone, Ad alone, prime/boost regimens with each antigen, prime/boost regimens with both antigens, and empty vector controls and then subjected to blood-stage challenge. The heterologous immunization regimen with the antigen pair was more protective than either antigen alone or both antigens delivered with a single vaccine platform, on the basis of their ability to induce the longest prepatent period and the longest time to the peak level of parasitemia, the lowest peak and mean levels of parasitemia, the smallest area under the parasitemia curve, and the highest self-cure rate. Overall, prechallenge MSP1 42 antibody titers strongly correlated with a decreased parasite burden. Nevertheless, a significant proportion of immunized animals developed anemia. In conclusion, the P. vivax plasmid DNA/Ad serotype 5 vaccine encoding blood-stage parasite antigens AMA1 and MSP1 42 in a heterologous prime/boost immunization regimen provided significant protection against blood-stage challenge in Aotus monkeys, indicating the suitability of these antigens and this regimen for further development. Copyright © 2017 American Society for Microbiology.

  15. Impact of the two-dose rubella vaccination regimen on incidence of rubella seronegativity in gravidae aged 25 years and younger.

    Science.gov (United States)

    Hui, Shuk Yi Annie; Sahota, Daljit S; Lao, Terence T

    2017-01-01

    This study compared the incidence of rubella seronegativity among gravidae of 25 year-old and younger, between those born in Hong Kong after 1983 when the two-dose rubella vaccination was implemented, versus gravidae born before, to examine the impact of the two-dose regimen. In this retrospective cohort study, the incidence of antenatal rubella seronegativity in our parturients managed in1997-2015 was analysed by their age from ≤16 to 25 years, and the effect of year of birth was determined adjusting for confounding factors including teenage status, obstetric history, anthropometric factors, and health parameters including anaemia, thalassaemia trait and hepatitis B carrier status. Among the 12743 gravidae, the 6103 gravidae born after 1983 had overall higher rubella seronegativity (9.1% versus 4.4%, OR 2.061, 95% CI 1.797-2.364), with significant difference (p = 0.006) and inverse correlation (prubella seronegativity except for those of ≤16 years. Regression analysis confirmed that birth after 1983 was independently associated with rubella seronegativity (aOR 2.207, 95% CI 1.902-2.562). There was a significant trend between rubella seronegativity with age in young gravidae, but the pattern was opposite between gravidae born after versus in/before 1983, with the former having a higher incidence of seronegativity at all ages. Young women covered by the two-dose rubella immunisation programme have a paradoxically higher incidence of rubella seronegativity.

  16. Protective efficacy of a virus-vectored multi-component vaccine against porcine reproductive and respiratory syndrome virus, porcine circovirus type 2 and swine influenza virus.

    Science.gov (United States)

    Tian, Debin; Sooryanarain, Harini; Matzinger, Shannon R; Gauger, Phil C; Karuppannan, Anbu K; Elankumaran, Subbiah; Opriessnig, Tanja; Meng, Xiang-Jin

    2017-12-01

    Porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV2) and swine influenza virus (SIV) are three of the most economically important swine pathogens, causing immense economic losses to the global swine industry. Monovalent commercial vaccines against each of the three viruses are routinely used in pig farms worldwide. A trivalent vaccine against all three pathogens would greatly simplify the vaccination programme and reduce the financial burden to the swine industry. In this study, by using an attenuated strain of PRRSV (strain DS722) as a live virus vector, we generated a multi-component vaccine virus, DS722-SIV-PCV2, which expresses the protective antigens from SIV and PCV2. The DS722-SIV-PCV2 trivalent vaccine virus replicates well, and expresses PCV2 capsid and SIV HA proteins in vitro. A subsequent vaccination and challenge study in 48 pigs revealed that the DS722-SIV-PCV2-vaccinated pigs had significantly reduced lung lesions and viral RNA loads when challenged with PRRSV. Upon challenge with PCV2, the vaccinated pigs had partially reduced lymphoid lesions and viral DNA loads, and when challenged with SIV the vaccinated pigs had significantly reduced acute respiratory sign scores. The results from this study demonstrate the potential of DS722-SIV-PCV2 as a candidate trivalent vaccine, and also shed light on exploring PRRSV as a potential live virus vaccine vector.

  17. Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS,S/AS01E Malaria Vaccine Integrated Within an Expanded Program on Immunization Regimen: A Phase II, Single-Center, Open, Controlled Trial in Infants in Malawi.

    Science.gov (United States)

    Witte, Desiree; Cunliffe, Nigel A; Turner, Ann M; Ngulube, Edward; Ofori-Anyinam, Opokua; Vekemans, Johan; Chimpeni, Philips; Lievens, Marc; Wilson, Trevor P; Njiram'madzi, Jenala; Mendoza, Yolanda Guerra; Leach, Amanda

    2018-05-01

    In a phase III trial, the RTS,S/AS01 malaria vaccine produced lower anti-circumsporozoite (CS) antibody titers when co-administered with Expanded Programme on Immunization vaccines (0-, 1- and 2-month schedule) at 6 to 12 weeks compared with 5 to 17 months at first vaccination. Alternative infant immunization schedules within the Expanded Programme on Immunization were investigated. This phase II, open, single-site (Blantyre, Malawi) trial was conducted in infants 1 to 7 days of age. Subjects were equally randomized across 7 groups to receive 3 doses of RTS,S/AS01E at time points that included ≤7 days, 6, 10, 14 and 26 weeks, and 9 months. All RTS,S/AS01E groups plus a control group (without RTS,S/AS01E) received Bacillus Calmette-Guérin + oral poliovirus vaccine at ≤7 days, diphtheria, tetanus, whole-cell pertussis, hepatitis B and Haemophilus influenzae type b vaccine + oral poliovirus vaccine at 6, 10, and 14 weeks and measles vaccine at 9 months; one RTS,S/AS01E group and the control additionally received hepatitis B vaccination at ≤7 days. Serum anti-CS antibody geometric mean concentration (GMC; enzyme-linked immunosorbent assay) and safety were assessed up to age 18 months. Of the 480 infants enrolled, 391 completed the study. No causally related serious adverse event was reported. A higher frequency of fever within 7 days of RTS,S/AS01E vaccination compared with control was observed. Compared with the standard 6-, 10-, 14-week schedule, anti-CS antibody GMC ratios post-dose 3 were significantly higher in the 10-, 14- and 26-week group only (ratio 1.80; 95% confidence interval, 1.24-2.60); RTS,S/AS01E vaccination at ≤7 days and 10 and 14 weeks produced significantly lower anti-CS GMCs (ratio 0.59; 95% confidence interval, 0.38-0.92). Initiation of RTS,S/AS01E vaccination above 6 weeks of age tended to improve anti-CS antibody responses. Neonatal vaccination was well tolerated but produced a comparatively lower immune response.

  18. Seasonal Influenza Vaccine Acceptance among Pregnant Women in Zhejiang Province, China: Evidence Based on Health Belief Model.

    Science.gov (United States)

    Hu, Yu; Wang, Ying; Liang, Hui; Chen, Yaping

    2017-12-11

    Background: Reasons for acceptance of seasonal influenza vaccine (SIV) vaccination among pregnant women in China are poorly understood. We assessed the intention to accept SIV among pregnant women in Zhejiang province, by using a self-administrated structured questionnaire developed on the basis of health belief model (HBM). Methods: From 1 January to 31 March 2014, pregnant women with ≥12 gestational weeks who attended antenatal clinics (ANCs) at public hospitals in 6 out of 90 districts were surveyed using a self-administered questionnaire that covered knowledge, attitudes, and beliefs related to SIV vaccination and influenza infection. We examined the associations between the acceptance of SIV vaccination and the demographic factors and HBM constructs using the logistic regression model, calculating the adjusted odds ratio (AOR). Results: Of the 1252 participants, 76.28% were willing to receive the SIV vaccination during their current pregnancy. High levels of perceived susceptibility of influenza (AOR = 1.75 (95%CI: 1.36-2.08)), high levels of perceived severity of influenza (AOR = 1.62 (95%CI: 1.25-1.95)), high level of perceived benefits of vaccination (AOR = 1.97 (95%CI: 1.76-2.21)), and high levels of cues to action were positively associated with the acceptance of SIV vaccination among pregnant women (AOR = 2.03 (95%CI: 1.70-2.69)), while high level of perceived barriers of vaccination was a negative determinant (AOR = 0.76 (95%CI: 0.62-0.94)). Conclusions: Poor knowledge and negative attitude towards SIV were associated with the poor acceptance of SIV. Health providers' recommendations were important to pregnant women's acceptance of SIV. Health education and direct communication strategies on SIV vaccination and influenza infection are necessary to improve the acceptance of SIV vaccination among pregnant women.

  19. [Viral contamination of polio vaccines in context of antivaccination mythology].

    Science.gov (United States)

    Mats, A N; Kuz'mina, M N; Cheprasova, E V

    2010-01-01

    Analysis of publications about real and suggested contamination of polio vaccines produced in 1950s and 1960s with simian viruses--SV40 and SIV--is performed. Factual data are discussed and antivaccination fictions about calamitous consequences of really occurred contamination with SV40 and concocted contamination with SIV are refuted.

  20. Priming with a simplified intradermal HIV-1 DNA vaccine regimen followed by boosting with recombinant HIV-1 MVA vaccine is safe and immunogenic: a phase IIa randomized clinical trial.

    Directory of Open Access Journals (Sweden)

    Patricia J Munseri

    Full Text Available Intradermal priming with HIV-1 DNA plasmids followed by HIV-1MVA boosting induces strong and broad cellular and humoral immune responses. In our previous HIVIS-03 trial, we used 5 injections with 2 pools of HIV-DNA at separate sites for each priming immunization. The present study explores whether HIV-DNA priming can be simplified by reducing the number of DNA injections and administration of combined versus separated plasmid pools.In this phase IIa, randomized trial, priming was performed using 5 injections of HIV-DNA, 1000 μg total dose, (3 Env and 2 Gag encoding plasmids compared to two "simplified" regimens of 2 injections of HIV-DNA, 600 μg total dose, of Env- and Gag-encoding plasmid pools with each pool either administered separately or combined. HIV-DNA immunizations were given intradermally at weeks 0, 4, and 12. Boosting was performed intramuscularly with 108 pfu HIV-MVA at weeks 30 and 46.129 healthy Tanzanian participants were enrolled. There were no differences in adverse events between the groups. The proportion of IFN-γ ELISpot responders to Gag and/or Env peptides after the second HIV-MVA boost did not differ significantly between the groups primed with 2 injections of combined HIV-DNA pools, 2 injections with separated pools, and 5 injections with separated pools (90%, 97% and 97%. There were no significant differences in the magnitude of Gag and/or Env IFN-γ ELISpot responses, in CD4+ and CD8+ T cell responses measured as IFN-γ/IL-2 production by intracellular cytokine staining (ICS or in response rates and median titers for binding antibodies to Env gp160 between study groups.A simplified intradermal vaccination regimen with 2 injections of a total of 600 μg with combined HIV-DNA plasmids primed cellular responses as efficiently as the standard regimen of 5 injections of a total of 1000 μg with separated plasmid pools after boosting twice with HIV-MVA.World Health Organization International Clinical Trials Registry

  1. Comparison of safety and immunogenicity of 2 WHO prequalified rabies vaccines administered by one week, 4 site intra dermal regimen (4-4-4-0-0) in animal bite cases.

    Science.gov (United States)

    Narayana, Ashwath; Manoharan, Aravind; Narayan, Madhusudana Shampur; Kalappa, Sudarshan Mysore; Biligumba, Gangaboraiah; Haradanahalli, Ravish; Anand, Ashwini Manoor

    2015-01-01

    The currently advocated rabies post-exposure prophylaxis regimens are of one month duration with reduced patient compliance. WHO recommended research on shortened vaccination regimens which have a practical and economic advantage over the existing regimens. Hence, the present study was undertaken to assess the safety and immunogenicity of 2 WHO prequalified rabies vaccines administered by one week, 4 site intra dermal regimen (4-4-4-0-0) in animal bite cases. This study was a comparative, open label, phase III, randomized clinical trial conducted at Anti rabies clinic, KIMS Hospital, Bangalore, India. The study was registered in Clinical Trials Registry of India (CTRI) bearing the registration number CTRI/2012/12/003230. Ninety subjects with category II/III animal bites/exposures were enrolled. Equine rabies immunoglobulin was administered to all category III exposures. 0.1 mL of either purified chick embryo cell vaccine (Rabipur) or purified verocell rabies vaccine (Verorab) was administered intradermally into 4 sites on days 0, 3 and 7 to all the study subjects. Serum of subjects collected on day 0, 14, 90 and 365 were analyzed for rabies virus neutralizing antibody (RVNA) concentration. The incidence of ADR in Rabipur and Verorab group was 2.96% and 1.14% respectively. In Rabipur group, geometric mean concentration (95% confidence interval) of RVNA was 14.5 (13.50, 15.57), 11.78 (11.27, 12.31) and 5.95 (5.50, 6.44) IU/mL on days 14, 90 and 365 respectively; In Verorab group geometric mean concentration (95% confidence interval) of RVNA was 14.43 (13.41, 15.53), 11.93 (11.47, 12.40) and 5.67 (5.29, 6.08) IU/mL on days 14, 90 and 365 respectively. In conclusion, Rabipur and Verorab were found to be safe, immunogenic and comparable with each other, when administered using one week, 4 site intradermal regimen (4-4-4-0-0) in animal bite cases.

  2. 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.

  3. Replicon particle vaccine protects swine against influenza.

    Science.gov (United States)

    Bosworth, B; Erdman, M M; Stine, D L; Harris, I; Irwin, C; Jens, M; Loynachan, A; Kamrud, K; Harris, D L

    2010-12-01

    An alphavirus derived replicon particle (RP) vaccine expressing the cluster IV H3N2 swine influenza virus (SIV) hemagglutinin (HA) gene induced protective immunity against homologous influenza virus challenge. However, pigs with maternal antibody had no protective immunity against challenge after vaccination with RP vaccines expressing HA gene alone or in combination with nucleoprotein gene. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. 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.

  5. Vaccine-induced immune responses against both Gag and Env improve control of simian immunodeficiency virus replication in rectally challenged rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Mauricio A Martins

    2017-07-01

    Full Text Available The ability to control lentivirus replication may be determined, in part, by the extent to which individual viral proteins are targeted by the immune system. Consequently, defining the antigens that elicit the most protective immune responses may facilitate the design of effective HIV-1 vaccines. Here we vaccinated four groups of rhesus macaques with a heterologous vector prime/boost/boost/boost (PBBB regimen expressing the following simian immunodeficiency virus (SIV genes: env, gag, vif, rev, tat, and nef (Group 1; env, vif, rev, tat, and nef (Group 2; gag, vif, rev, tat, and nef (Group 3; or vif, rev, tat, and nef (Group 4. Following repeated intrarectal challenges with a marginal dose of the neutralization-resistant SIVmac239 clone, vaccinees in Groups 1-3 became infected at similar rates compared to control animals. Unexpectedly, vaccinees in Group 4 became infected at a slower pace than the other animals, although this difference was not statistically significant. Group 1 exhibited the best post-acquisition virologic control of SIV infection, with significant reductions in both peak and chronic phase viremia. Indeed, 5/8 Group 1 vaccinees had viral loads of less than 2,000 vRNA copies/mL of plasma in the chronic phase. Vaccine regimens that did not contain gag (Group 2, env (Group 3, or both of these inserts (Group 4 were largely ineffective at decreasing viremia. Thus, vaccine-induced immune responses against both Gag and Env appeared to maximize control of immunodeficiency virus replication. Collectively, these findings are relevant for HIV-1 vaccine design as they provide additional insights into which of the lentiviral proteins might serve as the best vaccine immunogens.

  6. Prime-boost vaccine strategy against viral infections: Mechanisms and benefits.

    Science.gov (United States)

    Kardani, Kimia; Bolhassani, Azam; Shahbazi, Sepideh

    2016-01-20

    The essential goal of vaccination is to generate potent and long-term protection against diseases. Among different vaccine modalities, prime-boost vaccine strategies could enhance cellular and also humoral immunity in several animal models. These strategies have been applied for the development of vaccines against important infectious diseases such as HIV, SIV, HCV, HSV, and HBV indicating promising results even in clinical trials. Several factors including selection of antigen, type of vector, delivery route, dose, adjuvant, boosting regimen, the order of vector injection, and the intervals between different vaccinations influence the outcome of prime-boost immunization approaches. The reported data suggest that the prime-boost strategy as a combination of vaccines (i.e., heterologous prime-boost) may be better than a single vaccine for protection against infectious diseases. Indeed, in many cases, heterologous prime-boost can be more immunogenic than homologous prime-boost strategy. This review discusses the recent advances in prime-boost immunization strategies as well as their benefits and mechanisms of action. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Heterogeneity in neutralization sensitivities of viruses comprising the simian immunodeficiency virus SIVsmE660 isolate and vaccine challenge stock.

    Science.gov (United States)

    Lopker, Michael; Easlick, Juliet; Sterrett, Sarah; Decker, Julie M; Barbian, Hannah; Learn, Gerald; Keele, Brandon F; Robinson, James E; Li, Hui; Hahn, Beatrice H; Shaw, George M; Bar, Katharine J

    2013-05-01

    The sooty mangabey-derived simian immunodeficiency virus (SIV) strain E660 (SIVsmE660) is a genetically heterogeneous, pathogenic isolate that is commonly used as a vaccine challenge strain in the nonhuman primate (NHP) model of human immunodeficiency virus type 1 (HIV-1) infection. Though it is often employed to assess antibody-based vaccine strategies, its sensitivity to antibody-mediated neutralization has not been well characterized. Here, we utilize single-genome sequencing and infectivity assays to analyze the neutralization sensitivity of the uncloned SIVsmE660 isolate, individual viruses comprising the isolate, and transmitted/founder (T/F) viruses arising from low-dose mucosal inoculation of macaques with the isolate. We found that the SIVsmE660 isolate overall was highly sensitive to neutralization by SIV-infected macaque plasma samples (50% inhibitory concentration [IC50] isolate and T/F viruses arising from it that were substantially more resistant (>1,000-fold) to antibody neutralization and another fraction (~20%) that was intermediate in neutralization resistance. These findings may explain the variable natural history and variable protection afforded by heterologous Env-based vaccines in rhesus macaques challenged by high-dose versus low-dose SIVsmE660 inoculation regimens.

  8. First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus–Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens

    Science.gov (United States)

    Nyombayire, Julien; Anzala, Omu; Gazzard, Brian; Karita, Etienne; Bergin, Philip; Hayes, Peter; Kopycinski, Jakub; Omosa-Manyonyi, Gloria; Jackson, Akil; Bizimana, Jean; Farah, Bashir; Sayeed, Eddy; Parks, Christopher L.; Inoue, Makoto; Hironaka, Takashi; Hara, Hiroto; Shu, Tsugumine; Matano, Tetsuro; Dally, Len; Barin, Burc; Park, Harriet; Gilmour, Jill; Lombardo, Angela; Excler, Jean-Louis; Fast, Patricia; Laufer, Dagna S.; Cox, Josephine H.

    2017-01-01

    Background. We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)–vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. Methods. Sixty-five HIV-1–uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35–vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH). Results. All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot–determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (SLA and SHA) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8+ T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the SLA and SHA groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the ASH group. In contrast, the highest Gag-specific antibody titers were seen in the ASH group. Mucosal antibody responses were sporadic. Conclusions. SeV-Gag primed functional, durable HIV-specific T

  9. First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus-Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens.

    Science.gov (United States)

    Nyombayire, Julien; Anzala, Omu; Gazzard, Brian; Karita, Etienne; Bergin, Philip; Hayes, Peter; Kopycinski, Jakub; Omosa-Manyonyi, Gloria; Jackson, Akil; Bizimana, Jean; Farah, Bashir; Sayeed, Eddy; Parks, Christopher L; Inoue, Makoto; Hironaka, Takashi; Hara, Hiroto; Shu, Tsugumine; Matano, Tetsuro; Dally, Len; Barin, Burc; Park, Harriet; Gilmour, Jill; Lombardo, Angela; Excler, Jean-Louis; Fast, Patricia; Laufer, Dagna S; Cox, Josephine H

    2017-01-01

     We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine.  Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (S L A); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (S H A); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (AS H ); and priming and boosting with a higher-dose SeV-Gag given intranasally (S H S H ).  All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot-determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (S L A and S H A) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8 + T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the S L A and S H A groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the AS H group. In contrast, the highest Gag-specific antibody titers were seen in the AS H group. Mucosal antibody responses were sporadic.  SeV-Gag primed functional, durable HIV-specific T-cell responses and boosted antibody

  10. Complement-mediated virus infectivity neutralisation by HLA antibodies is associated with sterilising immunity to SIV challenge in the macaque model for HIV/AIDS.

    Science.gov (United States)

    Page, Mark; Quartey-Papafio, Ruby; Robinson, Mark; Hassall, Mark; Cranage, Martin; Stott, James; Almond, Neil

    2014-01-01

    Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed.

  11. Immunogenicity and safety of purified chick-embryo cell rabies vaccine under Zagreb 2-1-1 or 5-dose Essen regimen in Chinese children 6 to 17 years old and adults over 50 years: a randomized open-label study.

    Science.gov (United States)

    Li, RongCheng; Li, YanPing; Wen, ShuQing; Wen, HuiChun; Nong, Yi; Mo, Zhaojun; Xie, Fang; Pellegrini, Michele

    2015-01-01

    The aim of this Phase IIIb, open-label, randomized study was to demonstrate the non-inferiority of immune responses and to assess the safety of a purified chick-embryo cell rabies vaccine (PCECV) in healthy Chinese children (6 to 17 years) and older adults (≥51 years) following 2 alternative intramuscular (IM) simulated post-exposure prophylaxis (PEP) regimens: 4-dose Zagreb or 5-dose Essen regimen. Serum samples were collected prior to vaccination on Days 1 and 15 and on day 43 to assess immune response by rabies virus neutralizing antibody (RVNA) concentrations. Solicited adverse events (AEs) were recorded for up to 7 days following each vaccine dose, and unsolicited AEs throughout the entire study period. PCECV vaccination induced a strong immune response at Day 15, and the non-inferiority in immune response of the Zagreb vs. the Essen regimen was demonstrated in children and older adults. At Day 15,100% of children (N = 224), and 99% of subjects ≥51 years of age (N = 376) developed adequate RVNA concentrations (≥0.5 IU/mL); at Day 43 all subjects achieved RVNA concentrations ≥0.5 IU/mL, for both PEP regimens. The well-known tolerability and safety profile of the PCECV was again observed in this study following either Zagreb or Essen regimens. Rabies PEP vaccination with PCECV following a Zagreb regimen induced immune responses non-inferior to those of the Essen regimen, and had a similar safety and tolerability profile to the Essen regimen in Chinese children, adolescents, and adults over 51 years. ClinicalTrials.gov identifier: NCT01680016.

  12. B-Cell-Activating Factor and the B-Cell Compartment in HIV/SIV Infection

    Science.gov (United States)

    Borhis, Gwenoline; Trovato, Maria; Chaoul, Nada; Ibrahim, Hany M.; Richard, Yolande

    2017-01-01

    With the goal to design effective HIV vaccines, intensive studies focused on broadly neutralizing antibodies, which arise in a fraction of HIV-infected people. Apart from identifying new vulnerability sites in the viral envelope proteins, these studies have shown that a fraction of these antibodies are produced by self/poly-reactive B-cells. These findings prompted us to revisit the B-cell differentiation and selection process during HIV/SIV infection and to consider B-cells as active players possibly shaping the helper T-cell program within germinal centers (GCs). In this context, we paid a particular attention to B-cell-activating factor (BAFF), a key cytokine in B-cell development and immune response that is overproduced during HIV/SIV infection. As it does in autoimmune diseases, BAFF excess might contribute to the abnormal rescue of self-reactive B-cells at several checkpoints of the B-cell development and impair memory B-cell generation and functions. In this review, we first point out what is known about the functions of BAFF/a proliferation-inducing ligand and their receptors [B-cell maturation, transmembrane activator and CAML interactor (TACI), and BAFF-R], in physiological and pathophysiological settings, in mice and humans. In particular, we highlight recent results on the previously underappreciated regulatory functions of TACI and on the highly regulated production of soluble TACI and BAFF-R that act as decoy receptors. In light of recent data on BAFF, TACI, and BAFF-R, we then revisit the altered phenotypes and functions of B-cell subsets during the acute and chronic phase of HIV/SIV infection. Given the atypical phenotype and reduced functions of memory B-cells in HIV/SIV infection, we particularly discuss the GC reaction, a key checkpoint where self-reactive B-cells are eliminated and pathogen-specific memory B-cells and plasmablasts/cells are generated in physiological settings. Through its capacity to differentially bind and process BAFF-R and

  13. Immunogenicity and safety of purified vero cell rabies vaccine (PVRV) produced by Liaoning Cheng Da Co. under Zagreb 2-1-1 or 5-dose Essen regimen in Chinese adults aged 50 and above.

    Science.gov (United States)

    Wang, Jing; Luo, FengJi; Feng, ZiJian; Li, Li; Bai, YunHua; Ai, Xing; Ma, JianXin; Zhang, Zheng; Shi, NianMin

    2017-01-02

    Two kinds of regimens (2-1-1 and 1-1-1-1-1) can be selected after Zagreb regimen(2-1-1)of PVRV was officially approved in Beijing in January 2015. Up to now, the subjects for most studies about the comparison between Zagreb and Essen regimen are under 50 y old, rarely at and above. Aging of the immune system may result in decreasing efficacy of vaccination, especially for adults aged above 65-70 y. This study compared the safety and immunogenicity of the Zagreb and Essen regimen in Chinese adults aged 50 and above with the goal to provide a supplemental data for this age group. A total of 114 cases were divided into 2 groups randomly, received PVRV under the Zagreb and Essen regimens respectively. Serum samples were collected at D0, D7, D14, D42, D180 and D365 to determine the rabies serum neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT). Safety analyses were made by comparing the AEs in day-3, day-7, and day-(7 + 21) in Zagreb or day-(7 + 28) in Essen by gender and age cohorts. 617 blood samples were obtained. Two groups showed similar immunogenicity, the neutralizing antibody titer of all subjects at D14 and D42 showed >0.5 IU/ml. Under the same regimen, Subjects ≥65 y had lower GMC than those who <65 years from D7 to D365 within 2 groups. This difference was significantly shown on D7, D14, D180 in Zagreb group, and on D180 in Essen group (t = 2.38, p = 0.02; t = 3.78, p < 0.001; t = 2.30, p = 0.03; t = 4.42, p < 0.001). Subjects<65 years had higher seroconversion rate compared to ≥65 y on D7, D180 and D365 in both 2 groups, this difference was also significantly shown on D180, D365 in Zagreb group and on D180 in Essen group (χ 2 = 20.66, p < 0.001; χ 2 = 6.56, p = 0.02; χ 2 = 10.96, p = 0.002). Two regimens all showed favorable performances with mildly or common adverse events (AEs). The incidence of local AEs after 3 d in Essen group was higher than Zagreb group (χ 2 = 9.69, p = 0.002). The most common local AE was pain

  14. Persistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection.

    Directory of Open Access Journals (Sweden)

    Sama Adnan

    2016-12-01

    Full Text Available Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut and lymphoid tissues. Importantly, we also demonstrate the induction of a tissue-resident memory population of SIV-specific CD8 T cells in the vaginal mucosa, which was dependent on ongoing low-level antigenic stimulation. Moreover, we show that vaginal and serum antibody titers inversely correlated with post-challenge peak viral load, and we correlate the accumulation and affinity maturation of the antibody response to the duration of the vaccination period as well as to the SIVΔnef antigenic load. In conclusion, maturation of SIVΔnef-induced CD8 T cell and antibody responses, both propelled by viral persistence in the gut mucosa and secondary lymphoid tissues, results in protective immune responses that are able to interrupt viral transmission at mucosal portals of entry as well as potential sites of viral dissemination.

  15. A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of Electroporated HIV DNA with or without Interleukin 12 in Prime-Boost Combinations with an Ad35 HIV Vaccine in Healthy HIV-Seronegative African Adults.

    Directory of Open Access Journals (Sweden)

    Juliet Mpendo

    Full Text Available Strategies to enhance the immunogenicity of DNA vaccines in humans include i co-administration of molecular adjuvants, ii intramuscular administration followed by in vivo electroporation (IM/EP and/or iii boosting with a different vaccine. Combining these strategies provided protection of macaques challenged with SIV; this clinical trial was designed to mimic the vaccine regimen in the SIV study.Seventy five healthy, HIV-seronegative adults were enrolled into a phase 1, randomized, double-blind, placebo-controlled trial. Multi-antigenic HIV (HIVMAG plasmid DNA (pDNA vaccine alone or co-administered with pDNA encoding human Interleukin 12 (IL-12 (GENEVAX IL-12 given by IM/EP using the TriGrid Delivery System was tested in different prime-boost regimens with recombinant Ad35 HIV vaccine given IM.All local reactions but one were mild or moderate. Systemic reactions and unsolicited adverse events including laboratory abnormalities did not differ between vaccine and placebo recipients. No serious adverse events (SAEs were reported. T cell and antibody response rates after HIVMAG (x3 prime-Ad35 (x1 boost were independent of IL-12, while the magnitude of interferon gamma (IFN-γ ELISPOT responses was highest after HIVMAG (x3 without IL-12. The quality and phenotype of T cell responses shown by intracellular cytokine staining (ICS were similar between groups. Inhibition of HIV replication by autologous T cells was demonstrated after HIVMAG (x3 prime and was boosted after Ad35. HIV specific antibodies were detected only after Ad35 boost, although there was a priming effect with 3 doses of HIVMAG with or without IL-12. No anti-IL-12 antibodies were detected.The vaccines were safe, well tolerated and moderately immunogenic. Repeated administration IM/EP was well accepted. An adjuvant effect of co-administered plasmid IL-12 was not detected.ClinicalTrials.gov NCT01496989.

  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. The Earthquake‐Source Inversion Validation (SIV) Project

    KAUST Repository

    Mai, Paul Martin

    2016-04-27

    Finite-fault earthquake source inversions infer the (time-dependent) displacement on the rupture surface from geophysical data. The resulting earthquake source models document the complexity of the rupture process. However, multiple source models for the same earthquake, obtained by different research teams, often exhibit remarkable dissimilarities. To address the uncertainties in earthquake-source inversion methods and to understand strengths and weaknesses of the various approaches used, the Source Inversion Validation (SIV) project conducts a set of forward-modeling exercises and inversion benchmarks. In this article, we describe the SIV strategy, the initial benchmarks, and current SIV results. Furthermore, we apply statistical tools for quantitative waveform comparison and for investigating source-model (dis)similarities that enable us to rank the solutions, and to identify particularly promising source inversion approaches. All SIV exercises (with related data and descriptions) and statistical comparison tools are available via an online collaboration platform, and we encourage source modelers to use the SIV benchmarks for developing and testing new methods. We envision that the SIV efforts will lead to new developments for tackling the earthquake-source imaging problem.

  18. Influence of maternally-derived antibodies on live attenuated influenza vaccine efficacy in pigs.

    Science.gov (United States)

    Pyo, Hyun Mi; Hlasny, Magda; Zhou, Yan

    2015-07-17

    Vaccination during pregnancy is practiced in swine farms as one measure to control swine influenza virus (SIV) infection in piglets at an early age. Vaccine-induced maternal antibodies transfer to piglets through colostrum and stabilize the herd: however, maternally derived antibodies (MDA) interfere with immune response following influenza vaccination in piglets at the later stage of life. In addition, MDA is related to enhanced respiratory disease in SIV infection. Previously, we have developed a bivalent live attenuated influenza vaccine (LAIV) which harbors both H1 and H3 HAs. We demonstrated vaccination of this LAIV provided protection to homologous and heterologous SIV infection in pigs. In this study we aimed to investigate the influence of MDA on LAIV efficacy. To this end, SIV sero-negative sows were vaccinated with a commercial vaccine. After parturition, nursery piglets were vaccinated with LAIV intranasally or intramuscularly, and were then challenged with SIV. We report that MDA hampered serum antibody response induced by intramuscular vaccination but not by intranasal vaccination of the LAIV. Viral challenge in the presence of MDA caused exacerbated respiratory disease in unvaccinated piglets. In contrast, all LAIV vaccinated piglets were protected from homologous viral infection regardless of the route of vaccination and the presence of MDA. Our results demonstrated that LAIV conferred protection in the presence of MDA without inciting exacerbated respiratory disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Mapping the small RNA content of simian immunodeficiency virions (SIV.

    Directory of Open Access Journals (Sweden)

    Markus Brameier

    Full Text Available Recent evidence indicates that regulatory small non-coding RNAs are not only components of eukaryotic cells and vesicles, but also reside within a number of different viruses including retroviral particles. Using ultra-deep sequencing we have comprehensively analyzed the content of simian immunodeficiency virions (SIV, which were compared to mock-control preparations. Our analysis revealed that more than 428,000 sequence reads matched the SIV mac239 genome sequence. Among these we could identify 12 virus-derived small RNAs (vsRNAs that were highly abundant. Beside known retrovirus-enriched small RNAs, like 7SL-RNA, tRNA(Lys3 and tRNA(Lys isoacceptors, we also identified defined fragments derived from small ILF3/NF90-associated RNA snaR-A14, that were enriched more than 50 fold in SIV. We also found evidence that small nucleolar RNAs U2 and U12 were underrepresented in the SIV preparation, indicating that the relative number or the content of co-isolated exosomes was changed upon infection. Our comprehensive atlas of SIV-incorporated small RNAs provides a refined picture of the composition of retrovirions, which gives novel insights into viral packaging.

  20. The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study

    Science.gov (United States)

    Azman, Andrew S.; Luquero, Francisco J.; Ciglenecki, Iza; Grais, Rebecca F.; Sack, David A.; Lessler, Justin

    2015-01-01

    Background In 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both. Methods and Findings Using mathematical models we determined the minimum relative single-dose efficacy (MRSE) at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%–56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%). This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%–88%) for two doses and 44% (95% CI −27% to 76%) for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%–88%), which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943–86,205) cases in Zimbabwe, 78,317 (95% PI 57,435–100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490–3,170) cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture

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

    Science.gov (United States)

    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.

  2. Stability of the Gorilla Microbiome Despite SIV Infection

    Science.gov (United States)

    Moeller, Andrew H.; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H.; Ochman, Howard

    2015-01-01

    Simian Immunodeficiency Viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in fecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. Here, we examine the effects of SIVgor, a close relative of SIVcpz of chimpanzees and HIV-1 of humans, on the gut bacterial communities residing within wild gorillas, revealing that gorilla gut microbiomes are exceptionally robust to SIV infection. In contrast to the microbiomes of HIV-1 infected humans and SIVcpz-infected chimpanzees, SIVgor-infected gorilla microbiomes exhibit neither rises in the frequencies of opportunistic pathogens nor elevated rates of microbial turnover within individual hosts. Regardless of SIV infection status, gorilla microbiomes assort into enterotypes, one of which is compositionally analogous to those identified in humans and chimpanzees. The other gorilla enterotype appears specialized for a leaf-based diet and is enriched in environmentally derived bacterial genera. We hypothesize that the acquisition of this gorilla-specific enterotype was enabled by lowered immune-system control over the composition of the microbiome. Our results indicate differences between the pathology of SIVgor and SIVcpz/HIV-1 infections, demonstrating the utility of investigating host microbial ecology as a means for studying disease in wild primates of high conservation priority. PMID:25545295

  3. Rhesus macaque IFITM3 gene polymorphisms and SIV infection.

    Directory of Open Access Journals (Sweden)

    Michael Winkler

    Full Text Available Interferon-induced transmembrane proteins (IFITMs have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV and human immunodeficiency virus (HIV infection, respectively. Rhesus macaques (Macaca mulatta are commonly used to model human infections and the experimental inoculation of these animals with simian immunodeficiency virus (SIV is one of the best models for HIV/AIDS in humans. However, information on the role of IFITM3 in SIV infection of rhesus macaques is currently lacking. We show that rhesus macaque (rh IFITM3 inhibits SIV and FLUAV entry in cell culture, although with moderately reduced efficiency as compared to its human counterpart. We further report the identification of 16 polymorphisms in the rhIFITM3 gene, three of which were exonic and synonymous while the remainder was located in non-coding regions. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. In cohort 1, several intronic polymorphisms were significantly associated with virus load or survival. However, an association with both parameters was not observed and significance was lost in most cases when animals were stratified for the presence of MHC allele Mamu-A1*001. Moreover, no significant genotype-phenotype associations were detected in cohort 2. These results suggest that, although IFITM3 can inhibit SIV infection in cell culture, genetic variation in rhIFITM3 might have only a minor impact on the course of SIV infection in experimentally infected animals.

  4. 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

  5. Myocarditis in CD8-depleted SIV-infected rhesus macaques after short-term dual therapy with nucleoside and nucleotide reverse transcriptase inhibitors.

    Directory of Open Access Journals (Sweden)

    Lakshmanan Annamalai

    2010-12-01

    Full Text Available Although highly active antiretroviral therapy (HAART has dramatically reduced the morbidity and mortality associated with HIV infection, a number of antiretroviral toxicities have been described, including myocardial toxicity resulting from the use of nucleotide and nucleoside reverse transcriptase inhibitors (NRTIs. Current treatment guidelines recommend the use of HAART regimens containing two NRTIs for initial therapy of HIV-1 positive individuals; however, potential cardiotoxicity resulting from treatment with multiple NRTIs has not been addressed.We examined myocardial tissue from twelve CD8 lymphocyte-depleted adult rhesus macaques, including eight animals infected with simian immunodeficiency virus, four of which received combined antiretroviral therapy (CART consisting of two NRTIs [(9-R-2-Phosphonomethoxypropyl Adenine (PMPA and (+/--beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine (RCV] for 28 days. Multifocal infiltrates of mononuclear inflammatory cells were present in the myocardium of all macaques that received CART, but not untreated SIV-positive animals or SIV-negative controls. Macrophages were the predominant inflammatory cells within lesions, as shown by immunoreactivity for the macrophage markers Iba1 and CD68. Heart specimens from monkeys that received CART had significantly lower virus burdens than untreated animals (p<0.05, but significantly greater quantities of TNF-α mRNA than either SIV-positive untreated animals or uninfected controls (p<0.05. Interferon-γ (IFN-γ, IL-1β and CXCL11 mRNA were upregulated in heart tissue from SIV-positive monkeys, independent of antiretroviral treatment, but CXCL9 mRNA was only upregulated in heart tissue from macaques that received CART.These results suggest that short-term treatment with multiple NRTIs may be associated with myocarditis, and demonstrate that the CD8-depleted SIV-positive rhesus monkey is a useful model for studying the cardiotoxic effects of combined antiretroviral

  6. Human Vaccines & Immunotherapeutics

    OpenAIRE

    Riedmann, Eva M

    2014-01-01

    Measles vaccination: Targeted and non-targeted benefits CDC reports: 2-dose regimen of chickenpox vaccine is a success Positive preliminary results from the CAPiTA study Seasonal flu vaccine associate with reduced stroke risk HPV vaccine shown to halve cervical abnormalities Global prize for mobile mast vaccine storage project Developmental pathway of potent HIV-neutralizing antibodies Burkholderia vaccine: US Dep of Defense collaborates with Bavarian Nordic

  7. Overcoming maternal antibody interference by vaccination with human adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of swine influenza virus.

    Science.gov (United States)

    Wesley, Ronald D; Lager, Kelly M

    2006-11-26

    Sows and gilts lack immunity to human adenovirus 5 (Ad-5) vectored vaccines so immunogens of swine pathogens can be expressed with these vaccines in order to immunize suckling piglets that have interfering, maternally derived antibodies. In this study 7-day-old piglets, that had suckled H3N2 infected gilts, were sham-inoculated with a non-expressing Ad-5 vector or given a primary vaccination with replication-defective Ad-5 viruses expressed the H3 hemagglutinin and the nucleoprotein of swine influenza virus (SIV) subtype H3N2. The hemagglutination inhibition (HI) titer of the sham-inoculated group (n = 12) showed continued antibody decay whereas piglets vaccinated with Ad-5 SIV (n = 23) developed an active immune response by the second week post-vaccination. At 4 weeks-of-age when the HI titer of the sham-inoculated group had decayed to 45, the sham-inoculated group and half of the Ad-5 SIV vaccinated pigs were boosted with a commercial inactivated SIV vaccine. The boosted pigs that had been primed in the presence of maternal interfering antibodies had a strong anamnestic response while sham-inoculated pigs did not respond to the commercial vaccine. Two weeks after the booster vaccination the pigs were challenged with a non-homologous H3N2 virulent SIV. The efficacy of the vaccination protocol was demonstrated by abrogation of clinical signs, by clearance of challenge virus from pulmonary lavage fluids, by markedly reduced virus shedding in nasal secretions, and by the absence of moderate or severe SIV-induced lung lesions. These recombinant Ad-5 SIV vaccines are useful for priming the immune system to override the effects of maternally derived antibodies which interfere with conventional SIV vaccines.

  8. Vaccination-challenge studies with a Port Chalmers/73 (H3N2)-based swine influenza virus vaccine: Reflections on vaccine strain updates and on the vaccine potency test.

    Science.gov (United States)

    De Vleeschauwer, Annebel; Qiu, Yu; Van Reeth, Kristien

    2015-05-11

    The human A/Port Chalmers/1/73 (H3N2) influenza virus strain, the supposed ancestor of European H3N2 swine influenza viruses (SIVs), was used in most commercial SIV vaccines in Europe until recently. If manufacturers want to update vaccine strains, they have to perform laborious intratracheal (IT) challenge experiments and demonstrate reduced virus titres in the lungs of vaccinated pigs. We aimed to examine (a) the ability of a Port Chalmers/73-based commercial vaccine to induce cross-protection against a contemporary European H3N2 SIV and serologic cross-reaction against H3N2 SIVs from Europe and North America and (b) the validity of intranasal (IN) challenge and virus titrations of nasal swabs as alternatives for IT challenge and titrations of lung tissue in vaccine potency tests. Pigs were vaccinated with Suvaxyn Flu(®) and challenged by the IT or IN route with sw/Gent/172/08. Post-vaccination sera were examined in haemagglutination-inhibition assays against vaccine and challenge strains and additional H3N2 SIVs from Europe and North America, including an H3N2 variant virus. Tissues of the respiratory tract and nasal swabs were collected 3 days post challenge (DPCh) and from 0-7 DPCh, respectively, and examined by virus titration. Two vaccinations consistently induced cross-reactive antibodies against European H3N2 SIVs from 1998-2012, but minimal or undetectable antibody titres against North American viruses. Challenge virus titres in the lungs, trachea and nasal mucosa of the vaccinated pigs were significantly reduced after both IT and IN challenge. Yet the reduction of virus titres and nasal shedding was greater after IT challenge. The Port Chalmers/73-based vaccine still offered protection against a European H3N2 SIV isolated 35 years later and with only 86.9% amino acid homology in its HA1, but it is unlikely to protect against H3N2 SIVs that are endemic in North America. We use our data to reflect on vaccine strain updates and on the vaccine potency test

  9. Collapse of Cytolytic Potential in SIV-Specific CD8+ T Cells Following Acute SIV Infection in Rhesus Macaques.

    Directory of Open Access Journals (Sweden)

    Emily R Roberts

    2016-12-01

    Full Text Available Poor maintenance of cytotoxic factor expression among HIV-specific CD8+ T cells, in part caused by dysregulated expression of the transcription factor T-bet, is associated with HIV disease progression. However, the precise evolution and context in which CD8+ T cell cytotoxic functions become dysregulated in HIV infection remain unclear. Using the rhesus macaque (RM SIV infection model, we evaluated the kinetics of SIV-specific CD8+ T cell cytolytic factor expression in peripheral blood, lymph node, spleen, and gut mucosa from early acute infection through chronic infection. We identified rapid acquisition of perforin and granzyme B expression in SIV-specific CD8+ T cells in blood, secondary lymphoid tissues and gut mucosa that collapsed rapidly during the transition to chronic infection. The evolution of this expression profile was linked to low expression of T-bet and occurred independent of epitope specificity, viral escape patterns and tissue origin. Importantly, during acute infection SIV-specific CD8+ T cells that maintained T-bet expression retained the ability to express granzyme B after stimulation, but this relationship was lost in chronic infection. Together, these data demonstrate the loss of cytolytic machinery in SIV-specific CD8+ T cells in blood and at tissue sites of viral reservoir and active replication during the transition from acute to chronic infection. This phenomenon occurs despite persistent high levels of viremia suggesting that an inability to maintain properly regulated cytotoxic T cell responses in all tissue sites enables HIV/SIV to avoid immune clearance, establish persistent viral reservoirs in lymphoid tissues and gut mucosa, and lead ultimately to immunopathogenesis and death.

  10. Vaccinations

    Science.gov (United States)

    ... will not work well for all pets. Your veterinarian will determine a vaccination schedule most appropriate for ... programs, but in some instances may help your veterinarian determine if your pet has a reasonable expectation ...

  11. Strong mucosal immune responses in SIV infected macaques contribute to viral control and preserved CD4+ T-cell levels in blood and mucosal tissues.

    Science.gov (United States)

    Schultheiss, Tina; Schulte, Reiner; Sauermann, Ulrike; Ibing, Wiebke; Stahl-Hennig, Christiane

    2011-04-11

    Since there is still no protective HIV vaccine available, better insights into immune mechanism of persons effectively controlling HIV replication in the absence of any therapy should contribute to improve further vaccine designs. However, little is known about the mucosal immune response of this small unique group of patients. Using the SIV-macaque-model for AIDS, we had the rare opportunity to analyze 14 SIV-infected rhesus macaques durably controlling viral replication (controllers). We investigated the virological and immunological profile of blood and three different mucosal tissues and compared their data to those of uninfected and animals progressing to AIDS-like disease (progressors). Lymphocytes from blood, bronchoalveolar lavage (BAL), and duodenal and colonic biopsies were phenotypically characterized by polychromatic flow cytometry. In controllers, we observed higher levels of CD4+, CD4+CCR5+ and Gag-specific CD8+ T-cells as well as lower immune activation in blood and all mucosal sites compared to progressors. However, we could also demonstrate that immunological changes are distinct between these three mucosal sites.Intracellular cytokine staining demonstrated a significantly higher systemic and mucosal CD8+ Gag-specific cellular immune response in controllers than in progressors. Most remarkable was the polyfunctional cytokine profile of CD8+ lymphocytes in BAL of controllers, which significantly dominated over their blood response. The overall suppression of viral replication in the controllers was confirmed by almost no detectable viral RNA in blood and all mucosal tissues investigated. A strong and complex virus-specific CD8+ T-cell response in blood and especially in mucosal tissue of SIV-infected macaques was associated with low immune activation and an efficient suppression of viral replication. This likely afforded a repopulation of CD4+ T-cells in different mucosal compartments to almost normal levels. We conclude, that a robust SIV

  12. Vaccination with NS1-truncated H3N2 swine influenza virus primes T cells and confers cross-protection against an H1N1 heterosubtypic challenge in pigs

    Science.gov (United States)

    The diversity of contemporary swine influenza virus (SIV) strains impedes effective immunization of swine herds. Mucosally delivered, attenuated virus vaccines are one approach with potential to provide broad cross-protection. Reverse genetics-derived H3N2 SIV virus with truncated NS1 (NS1delta126 T...

  13. Partial protection of SIV-infected rhesus monkeys against superinfection with a heterologous SIV isolate

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette [Los Alamos National Laboratory

    2009-01-01

    Although there is increasing evidence that individuals already infected with human immunodeficiency virus type 1 (HIV-1) can be infected with a heterologous strain of the virus, the extent of protection against superinfection conferred by the first infection and the biologic consequences of superinfection are not well understood. We explored these questions in the simian immunodeficiency virus (SIV)/rhesus monkey model of HIV-1/AIDS. We infected cohorts of rhesus monkeys with either SIVmac251 or SIVsmE660 and then exposed animals to the reciprocal virus through intrarectal inoculations. Employing a quantitative real-time PCR assay, we determined the replication kinetics of the two strains of virus for 20 weeks. We found that primary infection with a replication-competent virus did not protect against acquisition of infection by a heterologous virus but did confer relative control of the superinfecting virus. In animals that became superinfected, there was a reduction in peak replication and rapid control of the second virus. The relative susceptibility to superinfection was not correlated with CD4(+) T-cell count, CD4(+) memory T-cell subsets, cytokine production by virus-specific CD8(+) or CD4(+) cells, or neutralizing antibodies at the time of exposure to the second virus. Although there were transient increases in viral loads of the primary virus and a modest decline in CD4(+) T-cell counts after superinfection, there was no evidence of disease acceleration. These findings indicate that an immunodeficiency virus infection confers partial protection against a second immunodeficiency virus infection, but this protection may be mediated by mechanisms other than classical adaptive immune responses.

  14. Properties of Si:V Annealed under Enhanced Hydrostatic Pressure

    International Nuclear Information System (INIS)

    Misiuk, A.; Wierzchowski, W.; Wieteska, K.; Barcz, A.; Bak-Misiuk, J.; Chow, L.; Vanfleet, R.; Prujszczyk, M.

    2011-01-01

    It is known that processing of silicon implanted with vanadium, Si:V, at high temperature-pressure, HT-HP, can lead to magnetic ordering within the V-enriched area. New data concerning structure of Si:V (prepared using V + doses, D = (1-5) x 10 15 cm -2 , and energy, E = 200 keV), as implanted and processed for up to 10 h at HT ≤ 1400 K under enhanced hydrostatic pressure, HP ≤ 1.1 GPa, are presented. In effect of implantation, amorphous (a-Si) area is produced near range of implanted species. Transmission electron microscopy, secondary ion mass spectrometry, X-ray, and synchrotron methods were used for sample characterisation. At HT-HP the a-Si layer is subjected to solid phase epitaxial re-growth. Depending on HP, distinct solid phase epitaxial re-growth and formation of VSi 2 are observed at HT ≥ 720 K. HP applied at processing results in the improved solid phase epitaxial re-growth in Si:V. This can be related, among others, to the effect of HP on diffusivity of V + and of implantation-induced point defects. Our results can be useful for development of the new family of diluted magnetic semiconductors. (author)

  15. Expansion of Simian Immunodeficiency Virus (SIV)-Specific CD8 T Cell Lines from SIV-Naive Mauritian Cynomolgus Macaques for Adoptive Transfer.

    Science.gov (United States)

    Mohns, Mariel S; Greene, Justin M; Cain, Brian T; Pham, Ngoc H; Gostick, Emma; Price, David A; O'Connor, David H

    2015-10-01

    CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). However, the specific qualities and characteristics of an effective CD8 T cell response remain unclear. Although targeting breadth, cross-reactivity, polyfunctionality, avidity, and specificity are correlated with HIV control, further investigation is needed to determine the precise contributions of these various attributes to CD8 T cell efficacy. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques (MCM). These cells exhibited an effector memory phenotype, produced cytokines in response to cognate antigen, and suppressed viral replication in vitro. We further cultured cell lines specific for four SIV-derived epitopes, Nef103-111 RM9, Gag389-394 GW9, Env338-346 RF9, and Nef254-262 LT9. These cell lines were up to 94.4% pure, as determined by major histocompatibility complex (MHC) tetramer analysis. After autologous transfer into two MCM recipients, expanded CD8 T cells persisted in peripheral blood and lung tissue for at least 24 weeks and trafficked to multiple extralymphoid tissues. However, these cells did not impact the acute-phase SIV load after challenge compared to historic controls. The expansion and autologous transfer of SIV-specific T cells into naive animals provide a unique model for exploring cellular immunity and the control of SIV infection and facilitate a systematic evaluation of therapeutic adoptive transfer strategies for eradication of the latent reservoir. CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Autologous adoptive transfer studies followed by SIV challenge may help define the critical elements of an effective T cell response to HIV and SIV infection. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus

  16. Expression of IL-18 by SIV does not modify the outcome of the antiviral immune response.

    Science.gov (United States)

    Giavedoni, Luis D; Velasquillo, M Cristina; Parodi, Laura M; Hubbard, Gene B; Hodara, Vida L

    2002-11-25

    Interleukin 18 (IL-18) is a proinflammatory cytokine expressed by several cell types, including activated dendritic cells and macrophages, that acts in synergy with IL-12 as an important amplifying factor for IFN-gamma production and Th1 development. To study the immunological and virological effects of IL-18 expression in the context of a lentiviral infection, we inoculated rhesus macaques with a high dose of replication-competent simian immunodeficiency virus (SIV) vectors carrying the rhesus IL-18 gene in the sense (SIV(IL-18)) or antisense (SIV(FIGI)) orientation. Both vectors behaved as attenuated viruses, resulting in low viral loads, induction of low and transient levels of inflammatory cytokines, no CD4(+) T cell depletion, and mild activation of T lymphocytes. Although IL-18-expressing virus could be isolated from some SIV(IL18)-infected macaques for 12 weeks postinfection, the anti-SIV humoral and cellular immune responses of macaques inoculated with SIV(IL18) and SIV(FIGI) were similar to each other, with the exception of an early IFN-gamma response in animals infected with SIV(IL18). In summary, expression of IL-18 during the acute phase of SIV infection does not increase viral replication or influence the outcome of the antiviral immune response.

  17. IgG Antibody Responses to Recombinant gp120 Proteins, gp70V1/V2 Scaffolds, and a CyclicV2 Peptide in Thai Phase I/II Vaccine Trials Using Different Vaccine Regimens.

    Science.gov (United States)

    Karasavvas, Nicos; Karnasuta, Chitraporn; Savadsuk, Hathairat; Madnote, Sirinan; Inthawong, Dutsadee; Chantakulkij, Somsak; Rittiroongrad, Surawach; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Thongcharoen, Prasert; Siriyanon, Vinai; Andrews, Charla A; Barnett, Susan W; Tartaglia, James; Sinangil, Faruk; Francis, Donald P; Robb, Merlin L; Michael, Nelson L; Ngauy, Viseth; de Souza, Mark S; Paris, Robert M; Excler, Jean-Louis; Kim, Jerome H; O'Connell, Robert J

    2015-11-01

    RV144 correlates of risk analysis showed that IgG antibodies to gp70V1V2 scaffolds inversely correlated with risk of HIV acquisition. We investigated IgG antibody responses in RV135 and RV132, two ALVAC-HIV prime-boost vaccine trials conducted in Thailand prior to RV144. Both trials used ALVAC-HIV (vCP1521) at 0, 1, 3, and 6 months and HIV-1 gp120MNgD and gp120A244gD in alum (RV135) or gp120SF2 and gp120CM235 in MF59 (RV132) at 3 and 6 months. We assessed ELISA binding antibodies to the envelope proteins (Env) 92TH023, A244gD and MNgD, cyclicV2, and gp70V1V2 CaseA2 (subtype B) and 92TH023 (subtype CRF01_AE), and Env-specific IgG1 and IgG3. Antibody responses to gp120 A244gD, MNgD, and gp70V1V2 92TH023 scaffold were significantly higher in RV135 than in RV132. Antibodies to gp70V1V2 CaseA2 were detected only in RV135 vaccine recipients and IgG1 and IgG3 antibody responses to A244gD were significantly higher in RV135. IgG binding to gp70V1V2 CaseA2 and CRF01_AE scaffolds was higher with the AIDSVAX(®)B/E boost but both trials showed similar rates of antibody decline post-vaccination. MF59 did not result in higher IgG antibody responses compared to alum with the antigens tested. However, notable differences in the structure of the recombinant proteins and dosage used for immunizations may have contributed to the magnitude and specificity of IgG induced by the two trials.

  18. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T

    2015-01-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...... diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin...... variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides...

  19. Factors Influencing Seasonal Influenza Vaccination Uptake in Emergency Medical Services Workers: A Concept Mapping Approach.

    Science.gov (United States)

    Subramaniam, Dipti P; Baker, Elizabeth A; Zelicoff, Alan P; Elliott, Michael B

    2016-08-01

    Seasonal influenza has serious impacts on morbidity and mortality and has a significant economic toll through lost workforce time and strains on the health system. Health workers, particularly emergency medical services (EMS) workers have the potential to transmit influenza to those in their care, yet little is known of the factors that influence EMS workers' decisions regarding seasonal influenza vaccination (SIV) uptake, a key factor in reducing potential for transmitting disease. This study utilizes a modified Theory of Planned Behavior (TPB) model as a guiding framework to explore the factors that influence SIV uptake in EMS workers. Concept mapping, which consists of six-stages (preparation, generation, structuring, representation, interpretation, and utilization) that use quantitative and qualitative approaches, was used to identify participants' perspectives towards SIV. This study identified nine EMS-conceptualized factors that influence EMS workers' vaccination intent and behavior. The EMS-conceptualized factors align with the modified TPB model and suggest the need to consider community-wide approaches that were not initially conceptualized in the model. Additionally, the expansion of non-pharmaceutical measures went above and beyond original conceptualization. Overall, this study demonstrates the need to develop customized interventions such as messages highlighting the importance of EMS workers receiving SIV as the optimum solution. EMS workers who do not intend to receive the SIV should be provided with accurate information on the SIV to dispel misconceptions. Finally, EMS workers should also receive interventions which promote voluntary vaccination, encouraging them to be proactive in the health decisions they make for themselves.

  20. Expression of myeloperoxidase in swine influenza virus (SIV)-infected neutrophils in lungs from pigs experimentally infected with SIV subtype H1N2.

    Science.gov (United States)

    Kim, Bongtae; Shin, Jeoung Hwa; Han, Kiwon; Seo, Hwi Won; Oh, Yeonsu; Kang, Ikjae; Park, Changhoon; Lee, Bog-Hieu; Jang, Jin Sil; Kim, Sung-Hoon; Chae, Chanhee

    2011-10-01

    The expression of myeloperoxidase (MPO) was examined in the swine influenza virus (SIV)-infected neutrophils in the lungs of pigs experimentally infected with swine influenza virus (SIV) subtype H1N2 by immunohistochemistry. Five pigs each from the infected and non-infected group were euthanized 1, 3, 5, 7, and 10 days post-inoculation (dpi). Immunohistochemical reactivity was mainly seen in neutrophils. The score for pulmonary histopathological lesions correlated with the score for MPO immunohistochemical reactivity (r ( s ) = 0.962, P < 0.01). In addition, the score for in situ hybridization of SIV nucleic acid correlated with the score for MPO immunohistochemical reactivity (r ( s ) = 0.976, P < 0.01). These results suggest neutrophils are one of the primary effector cells in the early phase of SIV infection in pigs.

  1. Sensitive method for the determination of different S(IV) species in cloud and fog water.

    Science.gov (United States)

    Lammel, G

    1996-08-01

    Suppressed ion chromatography has been applied to the determination of S(IV) species in cloud and fog water in the range 0.012-2.4 mg S(IV)-S/L. The samples have been preserved prior to storage and S(IV) species have been determined as hydroxy methanesulfonate (HMS) together with the low molecular weight carboxylic acid anions, formate and acetate. Samples have been divided and treated differently such that total S(IV) as well as the non-oxidizable fraction of S(IV) (as given by the reactivity with H(2)O(2), added in surplus) could be determined. The difference between the two corresponds to the S(IV) fraction subjected to oxididation, which is of paramount interest in cloud and fogwater chemistry.

  2. A next-generation, serum-free, highly purified Vero cell rabies vaccine is safe and as immunogenic as the reference vaccine Verorab® when administered according to a post-exposure regimen in healthy children and adults in China.

    Science.gov (United States)

    Li, Rongcheng; Huang, Lirong; Li, Jia; Mo, Zhaojun; He, Bin; Wang, Yunpeng; Wu, Xiaohong; Minutello, Maria; Guinet-Morlot, Françoise; Pichon, Sylvie

    2013-12-05

    As an evolution of its currently licensed rabies vaccine Verorab(®), Sanofi Pasteur has developed a next-generation, serum-free, highly purified Vero rabies vaccine (PVRV-NG). Through this Phase III clinical trial, we aimed to demonstrate the non-inferiority of PVRV-NG over Verorab when administered according to a post-exposure regimen and to assess its clinical safety. A total of 816 healthy subjects aged ≥10 years were randomized according to a 2:1 ratio to receive PVRV-NG or Verorab. Half of the subjects were aged 10-17 years, the other half were aged ≥18 years. All subjects were to receive 5 injections on days 0, 3, 7, 14 and 28. Three blood samples were taken for rabies virus neutralizing antibodies (RVNA) assessment, at baseline, on day 14 and day 42. Solicited adverse reactions (between injections 1, 2 and 3, and within 7 days post-injections 4 and 5) and adverse events (up to 28 days after the last injection) were collected for clinical safety assessment; serious adverse events were reported up to 6-months after the last injection. The proportion of subjects with an RVNA titer ≥0.5 IU/mL after the third injection of PVRV-NG was non-inferior to the proportion of those who received Verorab. PVRV-NG was shown to be as immunogenic as Verorab in each age range in the per-protocol and full analysis sets. PVRV-NG induced a strong immune response in both age ranges, with high RVNA levels and increased geometric mean titers compared to baseline after each measured time point. PVRV-NG had a satisfactory safety profile after each injection, similar to Verorab with regards to the nature, frequency, duration and severity of adverse events. Two serious adverse events were reported, none was related to vaccination. This trial demonstrated the immunogenic non-inferiority of PVRV-NG over Verorab and showed that both vaccines have similar safety profiles. This trial is registered at ClinicalTrials.gov (NCT01339312). This manuscript is the first full report of the

  3. Visualizing the Immune System: Providing Key Insights into HIV/SIV Infections

    Directory of Open Access Journals (Sweden)

    Jacob D. Estes

    2018-03-01

    Full Text Available Immunological inductive tissues, such as secondary lymphoid organs, are composed of distinct anatomical microenvironments for the generation of immune responses to pathogens and immunogens. These microenvironments are characterized by the compartmentalization of highly specialized immune and stromal cell populations, as well as the presence of a complex network of soluble factors and chemokines that direct the intra-tissue trafficking of naïve and effector cell populations. Imaging platforms have provided critical contextual information regarding the molecular and cellular interactions that orchestrate the spatial microanatomy of relevant cells and the development of immune responses against pathogens. Particularly in HIV/SIV disease, imaging technologies are of great importance in the investigation of the local interplay between the virus and host cells, with respect to understanding viral dynamics and persistence, immune responses (i.e., adaptive and innate inflammatory responses, tissue structure and pathologies, and changes to the surrounding milieu and function of immune cells. Merging imaging platforms with other cutting-edge technologies could lead to novel findings regarding the phenotype, function, and molecular signatures of particular immune cell targets, further promoting the development of new antiviral treatments and vaccination strategies.

  4. Personal decision-making criteria related to seasonal and pandemic A(H1N1 influenza-vaccination acceptance among French healthcare workers.

    Directory of Open Access Journals (Sweden)

    Lila Bouadma

    Full Text Available BACKGROUND: Influenza-vaccination rates among healthcare workers (HCW remain low worldwide, even during the 2009 A(H1N1 pandemic. In France, this vaccination is free but administered on a voluntary basis. We investigated the factors influencing HCW influenza vaccination. METHODS: In June-July 2010, HCW from wards of five French hospitals completed a cross-sectional survey. A multifaceted campaign aimed at improving vaccination coverage in this hospital group was conducted before and during the 2009 pandemic. Using an anonymous self-administered questionnaire, we assessed the relationships between seasonal (SIV and pandemic (PIV influenza vaccinations, and sociodemographic and professional characteristics, previous and current vaccination statuses, and 33 statements investigating 10 sociocognitive domains. The sociocognitive domains describing HCWs' SIV and PIV profiles were analyzed using the classification-and-regression-tree method. RESULTS: Of the HCWs responding to our survey, 1480 were paramedical and 401 were medical with 2009 vaccination rates of 30% and 58% for SIV and 21% and 71% for PIV, respectively (p<0.0001 for both SIV and PIV vaccinations. Older age, prior SIV, working in emergency departments or intensive care units, being a medical HCW and the hospital they worked in were associated with both vaccinations; while work shift was associated only with PIV. Sociocognitive domains associated with both vaccinations were self-perception of benefits and health motivation for all HCW. For medical HCW, being a role model was an additional domain associated with SIV and PIV. CONCLUSIONS: Both vaccination rates remained low. Vaccination mainly depended on self-determined factors and for medical HCW, being a role model.

  5. Innate Lymphoid Cells in HIV/SIV Infections

    Directory of Open Access Journals (Sweden)

    Spandan V. Shah

    2017-12-01

    Full Text Available Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  6. New candidate vaccines against blood-stage Plasmodium falciparum malaria: prime-boost immunization regimens incorporating human and simian adenoviral vectors and poxviral vectors expressing an optimized antigen based on merozoite surface protein 1

    NARCIS (Netherlands)

    Goodman, Anna L.; Epp, C.; Moss, D.; Holder, A. A.; Wilson, J. M.; Gao, G. P.; Long, C. A.; Remarque, E. J.; Thomas, A. W.; Ammendola, V.; Colloca, S.; Dicks, M. D. J.; Biswas, S.; Seibel, D.; van Duivenvoorde, L. M.; Gilbert, S. C.; Hill, A. V. S.; Draper, S. J.

    2010-01-01

    Although merozoite surface protein 1 (MSP-1) is a leading candidate vaccine antigen for blood-stage malaria, its efficacy in clinical trials has been limited in part by antigenic polymorphism and potentially by the inability of protein-in-adjuvant vaccines to induce strong cellular immunity. Here we

  7. Surveillance for adverse events following immunization (AEFI) for 7 years using a computerised vaccination system.

    Science.gov (United States)

    Alguacil-Ramos, A M; Muelas-Tirado, J; Garrigues-Pelufo, T M; Portero-Alonso, A; Diez-Domingo, J; Pastor-Villalba, E; Lluch-Rodrigo, J A

    2016-06-01

    The surveillance of vaccine safety is an essential requirement in vaccination programmes. Computerized immunization registries such as the Vaccination Information System (SIV) of Valencian Community (Spain) offer the opportunity to estimate the incidence of adverse events according to individual information. The aim of the study was to analyze adverse events following immunization reported through SIV from 2005 to 2011 by age, sex, type of vaccine and dose, and adverse event, and highlight the advantages of this type of reporting. A retrospective cohort study of subjects vaccinated in the Valencian Community using population health databases was carried out. Analysis of vaccinations and reported AEFI via SIV in Valencian Community was carried out. More than 13 million vaccines doses were administered during 2005 through 2011, the reporting rate of adverse events was 12.4/100,000 doses administered with the highest value in 2009 (27.4), with differences by age and sex. DTaP vaccine had the highest reporting in children (96.6/100,000) while influenza A(H1N1)pdm09 in adults (87.7/100,000). An increased reporting of adverse events was seen with DTaP in children 5-6 years of age, detected in real time, drove to swap this vaccine to a low dose Tdap which was followed by a decrease in administration site events. SIV demonstrates advantages for passive surveillance. Reporting rates by individual characteristics are calculated accurately and it also allows detecting shifts in reporting rate on real time for specific vaccines. The study shows that vaccines included in the routine vaccination schedule for children and adult vaccination programs are safe. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  8. HIV/SIV infection primes monocytes and dendritic cells for apoptosis.

    Directory of Open Access Journals (Sweden)

    Mireille Laforge

    2011-06-01

    Full Text Available Subversion or exacerbation of antigen-presenting cells (APC death modulates host/pathogen equilibrium. We demonstrated during in vitro differentiation of monocyte-derived macrophages and monocyte-derived dendritic cells (DCs that HIV sensitizes the cells to undergo apoptosis in response to TRAIL and FasL, respectively. In addition, we found that HIV-1 increased the levels of pro-apoptotic Bax and Bak molecules and decreased the levels of anti-apoptotic Mcl-1 and FLIP proteins. To assess the relevance of these observations in the context of an experimental model of HIV infection, we investigated the death of APC during pathogenic SIV-infection in rhesus macaques (RMs. We demonstrated increased apoptosis, during the acute phase, of both peripheral blood DCs and monocytes (CD14(+ from SIV(+RMs, associated with a dysregulation in the balance of pro- and anti-apoptotic molecules. Caspase-inhibitor and death receptors antagonists prevented apoptosis of APCs from SIV(+RMs. Furthermore, increased levels of FasL in the sera of pathogenic SIV(+RMs were detected, compared to non-pathogenic SIV infection of African green monkey. We suggest that inappropriate apoptosis of antigen-presenting cells may contribute to dysregulation of cellular immunity early in the process of HIV/SIV infection.

  9. 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.

  10. School-Based Influenza Vaccination: Health and Economic Impact of Maine's 2009 Influenza Vaccination Program.

    Science.gov (United States)

    Basurto-Dávila, Ricardo; Meltzer, Martin I; Mills, Dora A; Beeler Asay, Garrett R; Cho, Bo-Hyun; Graitcer, Samuel B; Dube, Nancy L; Thompson, Mark G; Patel, Suchita A; Peasah, Samuel K; Ferdinands, Jill M; Gargiullo, Paul; Messonnier, Mark; Shay, David K

    2017-12-01

    To estimate the societal economic and health impacts of Maine's school-based influenza vaccination (SIV) program during the 2009 A(H1N1) influenza pandemic. Primary and secondary data covering the 2008-09 and 2009-10 influenza seasons. We estimated weekly monovalent influenza vaccine uptake in Maine and 15 other states, using difference-in-difference-in-differences analysis to assess the program's impact on immunization among six age groups. We also developed a health and economic Markov microsimulation model and conducted Monte Carlo sensitivity analysis. We used national survey data to estimate the impact of the SIV program on vaccine coverage. We used primary data and published studies to develop the microsimulation model. The program was associated with higher immunization among children and lower immunization among adults aged 18-49 years and 65 and older. The program prevented 4,600 influenza infections and generated $4.9 million in net economic benefits. Cost savings from lower adult vaccination accounted for 54 percent of the economic gain. Economic benefits were positive in 98 percent of Monte Carlo simulations. SIV may be a cost-beneficial approach to increase immunization during pandemics, but programs should be designed to prevent lower immunization among nontargeted groups. © Health Research and Educational Trust.

  11. Defining HIV and SIV Reservoirs in Lymphoid Tissues

    Directory of Open Access Journals (Sweden)

    Claire Deleage

    2016-06-01

    Full Text Available A primary obstacle to an HIV-1 cure is long-lived viral reservoirs, which must be eliminated or greatly reduced. Cure strategies have largely focused on monitoring changes in T cell reservoirs in peripheral blood (PB, even though the lymphoid tissues (LT are primary sites for viral persistence. To track and discriminate viral reservoirs within tissue compartments we developed a specific and sensitive next-generation in situ hybridization approach to detect vRNA, including vRNA+ cells and viral particles (“RNAscope”, vDNA+ cells (“DNAscope” and combined vRNA and vDNA with immunohistochemistry to detect and phenotype active and latently infected cells in the same tissue section. RNAscope is highly sensitive with greater speed of analysis compared to traditional in situ hybridization. Highly sensitive and specific DNAscope detected SIV/HIV vDNA+ cells, including duplexed detection of vDNA and vRNA or immunophenotypic markers in the same section. Analysis of LT samples from macaques prior to and during combination antiretroviral therapy demonstrated that B cell follicles are an important anatomical compartment for both latent and active viral persistence during treatment. These new tools should allow new insights into viral reservoir biology and evaluation of cure strategies.

  12. Simian Immunodeficiency Virus (SIV-Specific Chimeric Antigen Receptor-T Cells Engineered to Target B Cell Follicles and Suppress SIV Replication

    Directory of Open Access Journals (Sweden)

    Kumudhini Preethi Haran

    2018-03-01

    Full Text Available There is a need to develop improved methods to treat and potentially cure HIV infection. During chronic HIV infection, replication is concentrated within T follicular helper cells (Tfh located within B cell follicles, where low levels of virus-specific CTL permit ongoing viral replication. We previously showed that elevated levels of simian immunodeficiency virus (SIV-specific CTL in B cell follicles are linked to both decreased levels of viral replication in follicles and decreased plasma viral loads. These findings provide the rationale to develop a strategy for targeting follicular viral-producing (Tfh cells using antiviral chimeric antigen receptor (CAR T cells co-expressing the follicular homing chemokine receptor CXCR5. We hypothesize that antiviral CAR/CXCR5-expressing T cells, when infused into an SIV-infected animal or an HIV-infected individual, will home to B cell follicles, suppress viral replication, and lead to long-term durable remission of SIV and HIV. To begin to test this hypothesis, we engineered gammaretroviral transduction vectors for co-expression of a bispecific anti-SIV CAR and rhesus macaque CXCR5. Viral suppression by CAR/CXCR5-transduced T cells was measured in vitro, and CXCR5-mediated migration was evaluated using both an in vitro transwell migration assay, as well as a novel ex vivo tissue migration assay. The functionality of the CAR/CXCR5 T cells was demonstrated through their potent suppression of SIVmac239 and SIVE660 replication in in vitro and migration to the ligand CXCL13 in vitro, and concentration in B cell follicles in tissues ex vivo. These novel antiviral immunotherapy products have the potential to provide long-term durable remission (functional cure of HIV and SIV infections.

  13. Kinetics of liver macrophages (Kupffer cells) in SIV-infected macaques

    International Nuclear Information System (INIS)

    Ahsan, Muhammad H.; Gill, Amy F.; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S.

    2013-01-01

    Since the liver drains antigens from the intestinal tract, and since the intestinal tract is a major site of viral replication, we examined the dynamics of liver macrophages (Kupffer cells) throughout SIV infection. Absolute numbers of Kupffer cells increased in the livers in acute infection, and in animals with AIDS. Significantly higher percentages of proliferating (BrdU+) Kupffer cells were detected in acute infection and in AIDS with similar trends in blood monocytes. Significantly higher percentages of apoptotic (AC3+) Kupffer cells were also found in acute and AIDS stages. However, productively infected cells were not detected in liver of 41/42 animals examined, despite abundant infected cells in gut and lymph nodes of all animals. Increased rates of Kupffer cell proliferation resulting in an increase in Kupffer cells without productive infection indicate SIV infection affects Kupffer cells, but the liver does not appear to be a major site of productive viral replication. - Highlights: • Kupffer cells increase in the liver of SIV-infected macaques. • Increased proliferation and apoptosis of Kupffer cells occurs in SIV infection. • Productively infected cells are rarely detected in the liver. • The liver is not a major site for SIV replication

  14. Capabilities of optical SIV technique in measurements of flow velocity vector field dynamics

    Science.gov (United States)

    Mikheev, N. I.; Dushin, N. S.; Saushin, I. I.

    2017-11-01

    The main difference between Smoke Image Velocimetry (SIV) technique and the conventional PIV is that higher concentration of tracer particles typical of smoke visualization techniques is used in SIV. Not separate particles but smoke structures with continuous pixel intensity are visible in the recorded images. Owing to better smoke reflectivity, higher spatial and temporal resolution is obtained in the case when relatively simple equipment (camera and laser) is used. It is simple enough to perform SIV measurements of velocity vector field dynamics at the frequency exceeding 15000 Hz, which offers new opportunities in unsteady flow examination. The paper describes fundamentals of SIV technique and gives some new results obtained using this method for the measurements that require high spatial and temporal resolution. The latter include frequency spectra of turbulent velocity fluctuations, turbulence dissipation profiles in the boundary layer and higher-order moments of velocity fluctuations. It has been shown that SIV technique considerably extends the potential of experimental studies of turbulence and flow structure in high-speed processes.

  15. Mechanisms of CD8+ T cell-mediated suppression of HIV/SIV replication.

    Science.gov (United States)

    McBrien, Julia Bergild; Kumar, Nitasha A; Silvestri, Guido

    2018-02-10

    In this article, we summarize the role of CD8 + T cells during natural and antiretroviral therapy (ART)-treated HIV and SIV infections, discuss the mechanisms responsible for their suppressive activity, and review the rationale for CD8 + T cell-based HIV cure strategies. Evidence suggests that CD8 + T cells are involved in the control of virus replication during HIV and SIV infections. During early HIV infection, the cytolytic activity of CD8 + T cells is responsible for control of viremia. However, it has been proposed that CD8 + T cells also use non-cytolytic mechanisms to control SIV infection. More recently, CD8 + T cells were shown to be required to fully suppress virus production in ART-treated SIV-infected macaques, suggesting that CD8 + T cells are involved in the control of virus transcription in latently infected cells that persist under ART. A better understanding of the complex antiviral activities of CD8 + T cells during HIV/SIV infection will pave the way for immune interventions aimed at harnessing these functions to target the HIV reservoir. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. HIV-1 Env DNA vaccine plus protein boost delivered by EP expands B- and T-cell responses and neutralizing phenotype in vivo.

    Directory of Open Access Journals (Sweden)

    Kar Muthumani

    Full Text Available An effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs, and the elicitation of antibody-dependent cellular cytotoxicity (ADCC. Previously, we demonstrated the induction of strong HIV/SIV cellular immune responses in macaques and humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP. However, the ability of this improved DNA approach to prime for relevant antibody responses has not been previously studied. Here, we investigate the immunogenicity of consensus DNA constructs encoding gp140 sequences from HIV-1 subtypes A, B, C and D in a DNA prime-protein boost vaccine regimen. Mice and guinea pigs were primed with single- and multi-clade DNA via EP and boosted with recombinant gp120 protein. Sera were analyzed for gp120 binding and induction of neutralizing antibody activity. Immunization with recombinant Env protein alone induced low-titer binding antibodies with limited neutralization breath. In contrast, the synthetic DNA prime-protein boost protocol induced significantly higher antibody binding titers. Furthermore, sera from DNA prime-protein boost groups were able to neutralize a broader range of viruses in a panel of tier 1 clade B viruses as well as multiple tier 1 clade A and clade C viruses. Further investigation of synthetic DNA prime plus adaptive EP plus protein boost appears warranted.

  17. Characterization of founder viruses in very early SIV rectal transmission.

    Science.gov (United States)

    Yuan, Zhe; Ma, Fangrui; Demers, Andrew J; Wang, Dong; Xu, Jianqing; Lewis, Mark G; Li, Qingsheng

    2017-02-01

    A better understanding of HIV-1 transmission is critical for developing preventative strategies. To that end, we analyzed 524 full-length env sequences of SIVmac251 at 6 and 10 days post intrarectal infection of rhesus macaques. There was no tissue compartmentalization of founder viruses across plasma, rectal and distal lymphatic tissues for most animals; however one animal has evidence of virus tissue compartmentalization. Despite identical viral inoculums, founder viruses were animal-specific, primarily derived from rare variants in the inoculum, and have a founder virus signature that can distinguish dominant founder variants from minor founder or untransmitted variants in the inoculum. Importantly, the sequences of post-transmission defective viruses were phylogenetically associated with competent viral variants in the inoculum and were mainly converted from competent viral variants by frameshift rather than APOBEC mediated mutations, suggesting the converting the transmitted viruses into defective viruses through frameshift mutation is an important component of rectal transmission bottleneck. Anorectal receptive intercourse is a common route of HIV-1 transmission and a better understanding of the transmission mechanisms is critical for developing HIV-1 preventative strategies. Here, we report that there is no tissue compartmentalization of founder viruses during very early rectal transmission of SIV in the majority of rhesus macaques and founder viruses are preferentially derived from rare variant in the inoculum. We also found that founder viruses are animal-specific despite identical viral inoculums. After viruses cross the mucosal barriers, the host further reduces viral diversity by converting some of the transmitted functional viruses into defective viruses through frameshift rather than APOBEC derived mutations. To our knowledge, this is the first study of founder viruses at multiple tissue sites during very early rectal transmission. Copyright © 2016

  18. Serum capacity to inhibit reverse transcriptase in vitro distinguishes HIV-1 infection from HIV-2 or SIV infection

    NARCIS (Netherlands)

    Wolfs, T. F.; Geelen, J. L.; Schellekens, H.; Barin, F.; Dekker, J. T.; Goudsmit, J.

    1989-01-01

    The inhibition of HIV-1 and SIV reverse transcriptase by human and rhesus macaque serum positive for HIV-1 or HIV-2/SIV antibodies was studied. The domain to which reverse transcriptase-inhibiting antibodies were elicited appeared to be highly antigenic. A total of 67% (48 of 72) of individuals had

  19. Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection

    DEFF Research Database (Denmark)

    Muenchhoff, Maximilian; Adland, Emily; Karimanzira, Owen

    2016-01-01

    Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preven...... over thousands of years in natural SIV hosts than those operating in HIV-infected adults.......Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors...... preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy-naïve children aged >5 years maintaining normal-for-Age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26...

  20. [Genetic diversity and phylogeographic distribution of SIV: how to understand the origin of HIV].

    Science.gov (United States)

    Peeters, Martine; Chaix, Marie-Laure; Delaporte, Eric

    2008-01-01

    Emergence of human immunodeficiency viruses HIV-1 and HIV-2 results from interspecies transmission from simian viruses SIV. SIVcpzPtt infecting chimpanzees, and from which the HIV-1 (subgroups M and N) is derived is still found in the Pan troglodytes troglodytes population of south Cameroon chimpanzees. The ancestor of HIV-1 group O, is found in the Gorilla residing in Western Africa, but chimpanzees are in fact the initial reservoir of the SIV viruses SIVgor, and it is still unclear whether the group O HIV-1 has been transmitted to humans by gorillas and/or chimpanzees. At least eight interspecies transmissions between and humans implicating SIVsmm (from sooty mangabey monkeys) have occurred, corresponding to the eight VIH-2 groups. Since habits of hunting and meat preparation in the bush still persistently expose humans in Africa to SIV infection, new interspecies transmission of these viruses remains a possibility.

  1. Development of a duplex real-time RT-qPCR assay to monitor genome replication, gene expression and gene insert stability during in vivo replication of a prototype live attenuated canine distemper virus vector encoding SIV gag.

    Science.gov (United States)

    Coleman, John W; Wright, Kevin J; Wallace, Olivia L; Sharma, Palka; Arendt, Heather; Martinez, Jennifer; DeStefano, Joanne; Zamb, Timothy P; Zhang, Xinsheng; Parks, Christopher L

    2015-03-01

    Advancement of new vaccines based on live viral vectors requires sensitive assays to analyze in vivo replication, gene expression and genetic stability. In this study, attenuated canine distemper virus (CDV) was used as a vaccine delivery vector and duplex 2-step quantitative real-time RT-PCR (RT-qPCR) assays specific for genomic RNA (gRNA) or mRNA have been developed that concurrently quantify coding sequences for the CDV nucleocapsid protein (N) and a foreign vaccine antigen (SIV Gag). These amplicons, which had detection limits of about 10 copies per PCR reaction, were used to show that abdominal cavity lymphoid tissues were a primary site of CDV vector replication in infected ferrets, and importantly, CDV gRNA or mRNA was undetectable in brain tissue. In addition, the gRNA duplex assay was adapted for monitoring foreign gene insert genetic stability during in vivo replication by analyzing the ratio of CDV N and SIV gag genomic RNA copies over the course of vector infection. This measurement was found to be a sensitive probe for assessing the in vivo genetic stability of the foreign gene insert. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Conditional virus replication as an approach to a safe live attenuated human immunodeficiency virus vaccine

    NARCIS (Netherlands)

    Berkhout, Ben; Verhoef, Koen; Marzio, Giuseppe; Klaver, Bep; Vink, Monique; Zhou, Xue; Das, Atze T.

    2002-01-01

    Despite intensive efforts, no safe and effective vaccine has been developed for the prophylaxis of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Studies with the simian immunodeficiency virus (SIV)/macaque model demonstrated that live attenuated viruses are the most

  3. [Electron microscopic investigation of CD4+ lymphocyte cell line C8166 after infection with simian immunodeficiency virus (SIV)].

    Science.gov (United States)

    Kaup, F J; Bingger, K; Mätz-Rensing, K; Stahl-Hennig, C; Schneider, T; Hofmann, P

    2003-04-01

    The SIV infection of rhesus macaques (Macaca mulatta) is the most appropriate animal model in HIV research. The permanent human T-cell line C8166 is used for in vitro SIV propagation. This paper describes ultrastructural features of the cells after infection with SIVmac. The C8166 cells are ultrastructurally characterized by a heterogenous morphology which is independent of the infection. SIV induced cell syncytia are observed 18 hours after infection. Viral particles and budding occur 48 hours p.i with a peak at the day 8. Viral particles present the typical lentiviral morphology. Using the monoclonal antibody anti SIVp28 and ultra small (0.8 nm) immunogold-silver enhancement technique, we are able to demonstrate SIV antigen immunoelectron microscopically. Therefore, this ultrastructural method is suitable to detect SIV antigen in in vivo experiments with C8166 cells from day 8 p.i. serving as positive control.

  4. Protection of guinea pigs by vaccination with a recombinant swinepox virus co-expressing HA1 genes of swine H1N1 and H3N2 influenza viruses.

    Science.gov (United States)

    Xu, Jiarong; Yang, Deji; Huang, Dongyan; Xu, Jiaping; Liu, Shichao; Lin, Huixing; Zhu, Haodan; Liu, Bao; Lu, Chengping

    2013-03-01

    Swine influenza (SI) is an acute respiratory infectious disease of swine caused by swine influenza virus (SIV). SIV is not only an important respiratory pathogen in pigs but also a potent threat to human health. Here, we report the construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs. Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and H3N2. The IFN-γ and IL-4 concentrations in the supernatant of lymphocytes stimulated with purified SIV HA1 antigen were significantly higher (P pigs against SIV H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung lesions. However, the control guinea pigs experienced distinct gross and micrographic lung lesions at 7 days post-challenge. Our data suggest that the recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.

  5. Validation of SIV measurements of turbulent characteristics in the separation region

    Science.gov (United States)

    Dushin, N. S.; Mikheev, N. I.; Dushina, O. A.; Zaripov, D. I.; Aslaev, A. K.

    2017-11-01

    Temporally and spatially resolved 2D measurements are important for the studies of complex turbulent flows. The recently developed SIV technique (Smoke Image Velocimetry), which is superior to PIV in some cases, can be used for this purpose. SIV validation results are presented for the steady turbulent backward-facing step flow measurements. Velocity profiles and Reynolds stress profiles are given for the regions of oncoming flow, reverse flow, flow reattachment and relaxation. The Reynolds number based on the step height and oncoming flow velocity at the boundary layer edge was Reh = 4834. The obtained data have been compared to LDA measurements and DNS.

  6. Low dose rectal inoculation of rhesus macaques by SIV SME660 or SIV MAC251 recapitulates human mucosal infection by HIV-1

    Energy Technology Data Exchange (ETDEWEB)

    Koraber, Bette [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory; Hraber, Peter [Los Alamos National Laboratory; Giorgi, E [Los Alamos National Laboratory; Bhattacharya, T [Los Alamos National Laboratory

    2009-01-01

    Recently, we developed a novel approach to the identification of transmitted or early founder HIV -1 genomes in acutely infected humans based on single genome amplification and sequencing. Here we tested this approach in 18 acutely infected Indian rhesus macaques to determine the molecular features of SIV transmission. Animals were inoculated intrarectally (IR) or intravenously (IV) 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 one to five weeks after infection. IR inoculation was followed by productive infection by one or few viruses (median 1; range 1-5) that diversified randomly with near star-like 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 few nuc1eotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder virus( es). IV infection was approximately 10,000-fold more efficient than IR 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.

  7. Stable multi-infection of splenocytes during SIV infection - the basis for continuous recombination

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    Schultz Anke

    2012-04-01

    Full Text Available Abstract Background Recombination is an important mechanism in the generation of genetic diversity of the human (HIV and simian (SIV immunodeficiency viruses. It requires the co-packaging of divergent RNA genomes into the same retroviral capsid and subsequent template switching during the reverse transcription reaction. By HIV-specific fluorescence in situ hybridization (FISH, we have previously shown that the splenocytes from 2 chronically infected patients with Castelman's disease were multi-infected and thus fulfill the in vivo requirements to generate genetic diversity by recombination. In order to analyze when multi-infection first occurs during a lentivirus infection and how the distribution of multi-infection evolves during the disease course, we now determined the SIV copy numbers from splenocytes of 11 SIVmac251-infected rhesus macaques cross-sectionally covering the time span of primary infection throughout to end-stage immunodeficiency. Results SIV multi-infection of single splenocytes was readily detected in all monkeys and all stages of the infection. Single-infected cells were more frequent than double- or triple- infected cells. There was no strong trend linking the copy number distribution to plasma viral load, disease stage, or CD4 cell counts. Conclusions SIV multi-infection of single cells is already established during the primary infection phase thus enabling recombination to affect viral evolution in vivo throughout the disease course.

  8. High Rate of Simian Immunodeficiency Virus (SIV Infections in Wild Chimpanzees in Northeastern Gabon

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    Vanina Boué

    2015-09-01

    Full Text Available The emergence of HIV-1 groups M, N, O, and P is the result of four independent cross-species transmissions between chimpanzees (cpz and gorillas (gor from central/south Cameroon and humans respectively. Although the first two SIVcpz were identified in wild-born captive chimpanzees in Gabon in 1989, no study has been conducted so far in wild chimpanzees in Gabon. To document the SIVcpz infection rate, genetic diversity, and routes of virus transmission, we analyzed 1458 faecal samples collected in 16 different locations across the country, and we conducted follow-up missions in two of them. We found 380 SIV antibody positive samples in 6 different locations in the north and northeast. We determined the number of individuals collected by microsatellite analysis and obtained an adjusted SIV prevalence of 39.45%. We performed parental analysis to investigate viral spread between and within communities and found that SIVs were epidemiologically linked and were transmitted by both horizontal and vertical routes. We amplified pol and gp41 fragments and obtained 57 new SIVcpzPtt strains from three sites. All strains, but one, clustered together within a specific phylogeographic clade. Given that these SIV positive samples have been collected nearby villages and that humans continue to encroach in ape’s territories, the emergence of a new HIV in this area needs to be considered.

  9. Lipopolysaccharide induces immune activation and SIV replication in rhesus macaques of Chinese origin.

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    Rong Bao

    Full Text Available BACKGROUND: Chronic immune activation is a hallmark of progressive HIV infection and a key determinant of immunodeficiency in HIV-infected individuals. Bacterial lipopolysaccharide (LPS in the circulation has been implicated as a key factor in HIV infection-related systemic immune activation. We thus investigate the impact of LPS on systemic immune activation in simian immunodeficiency virus (SIV-infected rhesus macaques of Chinese origin. METHODS: The animals were inoculated intravenously with SIVmac239. The levels of plasma viral load and host inflammatory cytokines in PBMC were measured by real-time RT-PCR. CD4/CD8 ratio and systemic immune activation markers were examined by flow cytometric analysis of PBMCs. White blood cell and neutrophil counts and C Reactive Protein levels were determined using biochemistry analyzer. The plasma levels of LPS were determined by Tachypleus Amebocyte Lysate (TAL test. RESULTS: The animals inoculated with SIVmac239 became infected as evidenced by the increased plasma levels of SIV RNA and decreased CD4/CD8 ratio. LPS administration of SIV-infected animals induced a transient increase of plasma SIV RNA and immune activation, which was indicated by the elevated expression of the inflammatory cytokines and CD4+HLA-DR+ T cells in PBMCs. CONCLUSIONS: These data support the concept that LPS is a driving factor in systemic immune activation of HIV disease.

  10. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

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    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.

  11. Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques

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    Fresh Lynn

    2004-07-01

    Full Text Available Abstract Background The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV in lactating rhesus macaques (Macaca mulatta as a model of natural breast milk transmission of HIV. Results Fourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i. and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days. Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation. Conclusion These studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the

  12. A field study on chemistry, S(IV) oxidation rates and vertical transport during fog conditions

    Science.gov (United States)

    Joos, F.; Baltensperger, U.

    An extensive fog study was carried out in the central plateu of Switzerland. Ninety-seven fog samples were collected along with aerosol filter and cascade impactor samples, and measurements of O 3, SO 2, NO, NO x, PAN, temperature, and wind speed and direction. Maximum levels in fogwater were 4.3, 4.4., 0.033, 1.7, 0.5, 0.024 and 9.2 mmol ℓ -1 for Cl -, NO 3-, NO 2-, SO 42-, S(IV), oxalate and NH 4+, respectively. pH varied between 2.9 and 7.1. Sixteen additional elements were determined in the fog samples by ICP. The sum of the concentrations of SO 42- and S(IV) agreed very with the total sulfur concentration as determined by ICP. A substantial excess of S(IV) (up to 0.2 mmol ℓ -1) compared to Henry and acid-base equilibrium calculations was found, which can probably be attributed to complex formations with aldehydes. S(IV) oxidation rates of up to 650 nmol ℓ -1 s -1 with ozone and of up to 100 nmol ℓ -1 s -1 with NO 2 were calculated. S(IV) oxidation due to PAN, NO 2- and Fe(III) was of minor importance. A substantial fraction of the major ions was present in the intersitial aerosol (aerosol particles < 4 μm) even during fog conditions. High correlations were found for NH 4+, NO 32-. From their ratios in the fog water and the aerosol (< 4 μm) it could be concluded that at least 40% of NO 3- and 20% of NH 4+ in fog water was due to gas phase scavenging. Increasing concentrations in fog water were found during fog dissipation. Concentrations decreased with increasing height. A vertical transport model including turbulent diffusion and droplet sedimentation is introduced, which matches the experimental data of this vertical profile.

  13. Metronomic chemotherapy regimens in oncology

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    M. Yu. Fedyanin

    2016-01-01

    Full Text Available Metronomic chemotherapy implies the regular use of cytotoxic agents in doses much smaller than the maximum tolerable doses for a long time. Preclinical experiments show that this treatment option has a many-sided (antiangiogenic, immunostimulating, and direct cytotoxic effect on tumor. Moreover, this approach has gained the widest acceptance in treating patients with metastatic breast cancer in clinical practice. By taking into account the high activity of angiogenesis in colon cancer progression, it is interesting to study the impact of metronomic chemotherapy regimens for this nosological entity as well. This literature review considers not only the history of metronomic chemotherapy, the mechanisms of action, and a range of drugs having an antitumor effect in the metronomic regimens, but also analyzes clinical trials of metronomic chemotherapy regimens in patients with metastatic colon cancer.

  14. Intradermal administration of viral vaccines.

    Science.gov (United States)

    Nagafuchi; Kashiwagi; Imayama; Hayashi; Niho

    1998-04-01

    Intradermal administration maybe useful in lowering the cost of vaccination against hepatitis B significantly, and may also be helpful for the rapid induction of antibodies, reversing non-responsiveness, improving postexposure prophylaxis and immunising immunocompromised people. In addition, delayed type hypersensitivity skin reaction to the vaccine could serve as a useful marker for the acquisition of T helper type 1 immunoreactivity in vivo. However, there are some disadvantages when using intradermal vaccinations, including the requirement for skilful administration, the absence of approval from licensing authorities, the development of local skin reactions and a lower antibody response when 1/10 of the standard vaccine dose is used. This requires that appropriate vaccination regimens, including the correct vaccine dosage, and vaccination schedule are followed. In the future, a similar vaccination strategy might also be applied for the prevention and control of other infectious diseases. Copyright 1998 John Wiley & Sons, Ltd.

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

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    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

  16. Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers.

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    Benjamin B Policicchio

    2016-09-01

    Full Text Available Viruses that persist despite seemingly effective antiretroviral treatment (ART and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the "shock and kill" strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to <10 SIV RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~106 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35-50 days, followed by in vivo experimental depletion of CD8+ cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~104 copies/ml peaking at 5-12 days post-treatment. CD8+ cell depletion resulted in a more robust viral rebound (107 copies/ml that was controlled upon CD8+ T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control

  17. Evaluación de la estructura factorial del Cuestionario de Valores Interpersonales (SIV

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    César Merino Soto

    2013-09-01

    Full Text Available El artículo evalúa la estructura factorial bajo los efectos del método ipsativo de respuesta, estudiados en el nivel de las subescalas del Cuestionario de Valores Interpersonales de Gordon (SIV, y las relaciones entre ellas, en una muestra de adolescentes entre 15 y 17 años de ambos sexos y procedentes de un colegio privado y estatal, representativos de los niveles socioeconómicos medio y bajo. Aunque el SIV ha sido una herramienta extensamente utilizada, no se reportado previamente un análisis de su estructura factorial en muestras Latinoamericanas. Mediante el análisis de componentes principales y el análisis factorial con un enfoque confirmatorio, se han identificado relaciones bipolares entre Independencia y Benevolencia, y Soporte y Conformidad. Se obtuvo también la confirmación del modelo de valores interpersonales propuesto por L. V. Gordon. En el análisis se consideró un aspecto que artificialmente puede haber influido en el patrón de correlaciones entre los componentes, esto es el método ipsativo de las preguntas del SIV. Finalmente, se discute sobre las medidas ipsativas y sus consecuencias en la interpretación de sus resultados. The present study evaluates the factorial structure, in the level of the subscales, of the Survey of Interpersonal Values (SIV, and the relationships among them, in a sample of adolescents between 15 and 17 years old of both sexes and from a private and public school, representative of low and middle socioeconomic levels. Although the SIV has been a widely used tool, there is no report of an analysis of its factorial structure in Latin-American samples. By means of the principal components analysis and the factorial analysis with a confirmatory approach, bipolar relationships have been identified between Independence and Benevolence, and Support and Conformity. The confirmation of the pattern of interpersonal values proposed by L. V. Gordon was also accomplished. An aspect considered in the

  18. The Adverse Effect of the 2-1-1 Regimen for Rabies PEP in Preschool Children.

    Science.gov (United States)

    Liu, Shu Qing; Tao, Xiao Yan; Yu, Peng Cheng; Jin, Chun Qiu; Yu, Hong Jie; Chen, Mei Shun; Zhu, Wu Yang

    2017-05-01

    Post-exposure prophylaxis (PEP) has proved to be the most important measure for rabies prevention and control. There is little information regarding adverse reactions to the Essen and 2-1-1 regimens in preschool children (aged 0-6). We reexamined the outcomes of 1,109 preschool children who were vaccinated using SPEEDA under the Essen regimen between January 2011 and December 2012 and 1,267 preschool children under the 2-1-1 regimen between January 2013 and December 2014. We find that, in preschool children, the febrile reaction after the first 2-dose injection in the 2-1-1 regimen was significantly higher than that induced by the first 1-dose in the Essen procedure. Thus, we recommend that the Essen regimen should still be used for rabies PEP in preschool children. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  19. Vaccines to combat smoking.

    Science.gov (United States)

    Bevins, Rick A; Wilkinson, Jamie L; Sanderson, Sam D

    2008-04-01

    Current US FDA-approved biological therapies for treating smoking target central nervous system processes. Although these therapies have had some success, relapse within a year is still high. Clearly additional strategies are needed to aid individuals in maintaining abstinence. We briefly discuss promising research using vaccines to combat smoking and then identify some potentially important directions for future research. Immunization with a nicotine vaccine generates drug-specific antibodies that sequester some of the nicotine in the peripheral circulation preventing it from entering the brain, thus decreasing its addictive effects. Albeit promising, much more research is necessary to identify more efficacious vaccine designs and formulations, as well as optimal immunization regimens. A further understanding of the factors contributing to the substantial individual differences in immunogenicity to these vaccines and how to best use vaccines in combination with other treatment strategies will increase the success of intervention efforts.

  20. HPV vaccine

    Science.gov (United States)

    Vaccine - HPV; Immunization - HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; Abnormal ...

  1. Lower vaccine uptake amongst older individuals living alone: A systematic review and meta-analysis of social determinants of vaccine uptake.

    Science.gov (United States)

    Jain, Anu; van Hoek, A J; Boccia, Delia; Thomas, Sara L

    2017-04-25

    Vaccination is a key intervention to reduce infectious disease mortality and morbidity amongst older individuals. Identifying social factors for vaccine uptake enables targeted interventions to reduce health inequalities. To systematically appraise and quantify social factors associated with vaccine uptake amongst individuals aged ≥60years from Europe. We searched Medline and Embase from inception to 24/02/2016. The association of vaccine uptake was examined for social factors relevant at an individual level, to provide insight into individuals' environment and enable development of targeted interventions by healthcare providers to deliver equitable healthcare. Factors included: living alone, marital status, education, income, vaccination costs, area-level deprivation, social class, urban versus rural residence, immigration status and religion. Between-study heterogeneity for each factor was identified using I 2 -statistics and Q-statistics, and investigated by stratification and meta-regression analysis. Meta-analysis was conducted, when appropriate, using fixed- or random-effects models. From 11,754 titles, 35 eligible studies were identified (uptake of: seasonal influenza vaccine (SIV) only (n=27) or including pneumococcal vaccine (PV) (n=5); herpes zoster vaccine (n=1); pandemic influenza vaccine (n=1); PV only (n=1)). Higher SIV uptake was reported for individuals not living alone (summary odds ratios (OR)=1.39 (95% confidence interval (CI): 1.16-1.68). Lower SIV uptake was observed in immigrants and in more deprived areas: summary OR=0.57 (95%CI: 0.47-0.68) and risk ratio=0.93 (95%CI: 0.92-0.94) respectively. Higher SIV uptake was associated with higher income (OR=1.26 (95%CI: 1.08-1.47)) and higher education (OR=1.05 (95%CI: 1-1.11)) in adequately adjusted studies. Between-study heterogeneity did not appear to result from variation in categorisation of social factors, but for education was partly explained by varying vaccination costs (meta

  2. Analysis of the functional compatibility of SIV capsid sequences in the context of the FIV gag precursor.

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    César A Ovejero

    Full Text Available The formation of immature lentiviral particles is dependent on the multimerization of the Gag polyprotein at the plasma membrane of the infected cells. One key player in the virus assembly process is the capsid (CA domain of Gag, which establishes the protein-protein interactions that give rise to the hexagonal lattice of Gag molecules in the immature virion. To gain a better understanding of the functional equivalence between the CA proteins of simian and feline immunodeficiency viruses (SIV and FIV, respectively, we generated a series of chimeric FIV Gag proteins in which the CA-coding region was partially or totally replaced by its SIV counterpart. All the FIV Gag chimeras were found to be assembly-defective; however, all of them are able to interact with wild-type SIV Gag and be recruited into extracellular virus-like particles, regardless of the SIV CA sequences present in the chimeric FIV Gag. The results presented here markedly contrast with our previous findings showing that chimeric SIVs carrying FIV CA-derived sequences are assembly-competent. Overall, our data support the notion that although the SIV and FIV CA proteins share 51% amino acid sequence similarity and exhibit a similar organization, i.e., an N-terminal domain joined by a flexible linker to a C-terminal domain, their functional exchange between these different lentiviruses is strictly dependent on the context of the recipient Gag precursor.

  3. Protection in simian immunodeficiency virus-vaccinated monkeys correlates with anti-HLA class I antibody response

    OpenAIRE

    1992-01-01

    Our earlier reports demonstrated that Cynomolgus macaques vaccinated with either inactivated partially purified simian immunodeficiency virus (SIV), fixed SIV-infected C8166 (a human T lymphoblastoid cell line) cells, or fixed uninfected C8166 cells can be protected against a challenge infection with the 32H isolate of SIVmac 251 (grown in C8166) (Stott, E. J., W. L. Chan, K. H. G. Mills, M. Page, F. Taffs, M. Cranage, P. Greenway, and P. Kitchin. 1990. Lancet. 336:1538; Stott, E. J., P. A. K...

  4. Hypercytotoxicity and rapid loss of NKp44+ innate lymphoid cells during acute SIV infection.

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    Haiying Li

    2014-12-01

    Full Text Available HIV/SIV infections break down the integrity of the gastrointestinal mucosa and lead to chronic immune activation and associated disease progression. Innate lymphoid cells (ILCs, distinguishable by high expression of NKp44 and RORγt, play key roles in mucosal defense and homeostasis, but are depleted from gastrointestinal (GI tract large bowel during chronic SIV infection. However, less is known about the kinetics of ILC loss, or if it occurs systemically. In acute SIV infection, we found a massive, up to 8-fold, loss of NKp44+ILCs in all mucosae as early as day 6 post-infection, which was sustained through chronic disease. Interestingly, no loss of ILCs was observed in mucosa-draining lymph nodes. In contrast, classical NK cells were not depleted either from gut or draining lymph nodes. Both ILCs and NK cells exhibited significantly increased levels of apoptosis as measured by increased Annexin-V expression, but while classical NK cells also showed increased proliferation, ILCs did not. Interestingly, ILCs, which are normally noncytolytic, dramatically upregulated cytotoxic functions in acute and chronic infection and acquired a polyfunctional phenotype secreting IFN-γ, MIP1-β, and TNF-α, but decreased production of the prototypical cytokine, IL-17. Classical NK cells had less dramatic functional change, but upregulated perforin expression and increased cytotoxic potential. Finally, we show that numerical and functional loss of ILCs was due to increased apoptosis and ROR γt suppression induced by inflammatory cytokines in the gut milieu. Herein we demonstrate the first evidence for acute, systemic, and permanent loss of mucosal ILCs during SIV infection associated with reduction of IL-17. The massive reduction of ILCs involves apoptosis without compensatory de novo development/proliferation, but the full mechanism of depletion and the impact of functional change so early in infection remain unclear.

  5. Plasmon resonance enhanced temperature-dependent photoluminescence of Si-V centers in diamond

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Shaoheng [State Key Laboratory of Superhard Materials, Jilin University, Changchun 130012 (China); State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012 (China); Song, Jie; Wang, Qiliang; Liu, Junsong; Li, Hongdong, E-mail: hdli@jlu.edu.cn [State Key Laboratory of Superhard Materials, Jilin University, Changchun 130012 (China); Zhang, Baolin [State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012 (China)

    2015-11-23

    Temperature dependent optical property of diamond has been considered as a very important factor for realizing high performance diamond-based optoelectronic devices. The photoluminescence feature of the zero phonon line of silicon-vacancy (Si-V) centers in Si-doped chemical vapor deposited single crystal diamond (SCD) with localized surface plasmon resonance (LSPR) induced by gold nanoparticles has been studied at temperatures ranging from liquid nitrogen temperature to 473 K, as compared with that of the SCD counterpart in absence of the LSPR. It is found that with LSPR the emission intensities of Si-V centers are significantly enhanced by factors of tens and the magnitudes of the redshift (width) of the emissions become smaller (narrower), in comparison with those of normal emissions without plasmon resonance. More interestingly, these strong Si-V emissions appear remarkably at temperatures up to 473 K, while the spectral feature was not reported in previous studies on the intrinsic Si-doped diamonds when temperatures are higher than room temperature. These findings would lead to reaching high performance diamond-based devices, such as single photon emitter, quantum cryptography, biomarker, and so forth, working under high temperature conditions.

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

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    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.

  7. Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

    Science.gov (United States)

    Simon, Liz; Song, Keijing; Vande Stouwe, Curtis; Hollenbach, Andrew; Amedee, Angela; Mohan, Mahesh; Winsauer, Peter; Molina, Patricia

    2016-03-01

    Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

  8. Intravenous and intramuscular magnesium sulphate regimens in ...

    African Journals Online (AJOL)

    1993-09-03

    Sep 3, 1993 ... parenterally, usually according to one of two popular regimens: the intramuscular (IM) regimen introduced by. Pritchard' and a continuous intravenous (IV) infusion described by Zuspan! Sibai et a/.3 have reported that lower serum magnesium values are achieved with Zuspan's regimen (maintenance dose ...

  9. Multiple Low-Dose Challenges in a Rhesus Macaque AIDS Vaccine Trial Result in an Evolving Host Response That Affects Protective Outcome

    Science.gov (United States)

    Selinger, Christian; Strbo, Natasa; Gonzalez, Louis; Aicher, Lauri; Weiss, Jeffrey M.; Law, G. Lynn; Palermo, Robert E.; Vaccari, Monica; Franchini, Genoveffa; Podack, Eckhard R.

    2014-01-01

    Using whole-blood transcriptional profiling, we investigated differences in the host response to vaccination and challenge in a rhesus macaque AIDS vaccine trial. Samples were collected from animals prior to and after vaccination with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig loaded with simian immunodeficiency virus (SIV) peptides, either alone or in combination with a SIV-gp120 protein boost. Additional samples were collected following multiple low-dose rectal challenges with SIVmac251. Animals in the boosted group had a 73% reduced risk of infection. Surprisingly, few changes in gene expression were observed during the vaccination phase. Focusing on postchallenge comparisons, in particular for protected animals, we identified a host response signature of protection comprised of strong interferon signaling after the first challenge, which then largely abated after further challenges. We also identified a host response signature, comprised of early macrophage-mediated inflammatory responses, in animals with undetectable viral loads 5 days after the first challenge but with unusually high viral titers after subsequent challenges. Statistical analysis showed that prime-boost vaccination significantly lowered the probability of infection in a time-consistent manner throughout several challenges. Given that humoral responses in the prime-boost group were highly significant prechallenge correlates of protection, the strong innate signaling after the first challenge suggests that interferon signaling may enhance vaccine-induced antibody responses and is an important contributor to protection from infection during repeated low-dose exposure to SIV. PMID:25274805

  10. Dietary Enterococcus faecium NCIMB 10415 and zinc oxide stimulate immune reactions to trivalent influenza vaccination in pigs but do not affect virological response upon challenge infection.

    Science.gov (United States)

    Wang, Zhenya; Burwinkel, Michael; Chai, Weidong; Lange, Elke; Blohm, Ulrike; Breithaupt, Angele; Hoffmann, Bernd; Twardziok, Sven; Rieger, Juliane; Janczyk, Pawel; Pieper, Robert; Osterrieder, Nikolaus

    2014-01-01

    Swine influenza viruses (SIV) regularly cause significant disease in pigs worldwide. Since there is no causative treatment of SIV, we tested if probiotic Enterococcus (E.) faecium NCIMB 10415 or zinc (Zn) oxide as feed supplements provide beneficial effects upon SIV infection in piglets. Seventy-two weaned piglets were fed three different diets containing either E. faecium or different levels of Zn (2500 ppm, Zn(high); 50 ppm, Zn(low)). Half of the piglets were vaccinated intramuscularly (VAC) twice with an inactivated trivalent SIV vaccine, while all piglets were then infected intranasally with H3N2 SIV. Significantly higher weekly weight gains were observed in the E. faecium group before virus infection, and piglets in Zn(high) and E. faecium groups gained weight after infection while those in the control group (Zn(low)) lost weight. Using ELISA, we found significantly higher H3N2-specific antibody levels in the E. faecium+VAC group 2 days before and at the day of challenge infection as well as at 4 and 6 days after challenge infection. Higher hemagglutination inhibition (HI) titers were also observed in the Zn(high)+VAC and E. faecium+VAC groups at 0, 1 and 4 days after infection. However, there were no significant differences in virus shedding and lung lesions between the dietary groups. Using flow cytometry analysis significantly higher activated T helper cells and cytotoxic T lymphocyte percentages in the PBMCs were detected in the Zn(high) and E. faecium groups at single time points after infection compared to the Zn(low) control group, but no prolonged effect was found. In the BAL cells no influence of dietary supplementation on immune cell percentages could be detected. Our results suggest that feeding high doses of zinc oxide and particularly E. faecium could beneficially influence humoral immune responses after vaccination and recovery from SIV infection, but not affect virus shedding and lung pathology.

  11. Dietary Enterococcus faecium NCIMB 10415 and zinc oxide stimulate immune reactions to trivalent influenza vaccination in pigs but do not affect virological response upon challenge infection.

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    Zhenya Wang

    Full Text Available Swine influenza viruses (SIV regularly cause significant disease in pigs worldwide. Since there is no causative treatment of SIV, we tested if probiotic Enterococcus (E. faecium NCIMB 10415 or zinc (Zn oxide as feed supplements provide beneficial effects upon SIV infection in piglets. Seventy-two weaned piglets were fed three different diets containing either E. faecium or different levels of Zn (2500 ppm, Zn(high; 50 ppm, Zn(low. Half of the piglets were vaccinated intramuscularly (VAC twice with an inactivated trivalent SIV vaccine, while all piglets were then infected intranasally with H3N2 SIV. Significantly higher weekly weight gains were observed in the E. faecium group before virus infection, and piglets in Zn(high and E. faecium groups gained weight after infection while those in the control group (Zn(low lost weight. Using ELISA, we found significantly higher H3N2-specific antibody levels in the E. faecium+VAC group 2 days before and at the day of challenge infection as well as at 4 and 6 days after challenge infection. Higher hemagglutination inhibition (HI titers were also observed in the Zn(high+VAC and E. faecium+VAC groups at 0, 1 and 4 days after infection. However, there were no significant differences in virus shedding and lung lesions between the dietary groups. Using flow cytometry analysis significantly higher activated T helper cells and cytotoxic T lymphocyte percentages in the PBMCs were detected in the Zn(high and E. faecium groups at single time points after infection compared to the Zn(low control group, but no prolonged effect was found. In the BAL cells no influence of dietary supplementation on immune cell percentages could be detected. Our results suggest that feeding high doses of zinc oxide and particularly E. faecium could beneficially influence humoral immune responses after vaccination and recovery from SIV infection, but not affect virus shedding and lung pathology.

  12. Revisiting a quarter of a century of simian immunodeficiency virus (SIV-associated cardiovascular diseases at the German Primate Center

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    M. Mietsch

    2017-06-01

    Full Text Available Human immunodeficiency virus (HIV comorbidities have become clinically more important due to antiretroviral therapy. Although therapy increases life expectancy, it does not completely suppress immune activation and its associated complications. The simian immunodeficiency virus (SIV-infected rhesus macaque (Macaca mulatta represents a valuable model for the investigation of SIV-associated diseases. Although cardiovascular (CV changes are common in HIV-infected patients, there are only a few reports on the incidence of CV findings in SIV-infected animals. In addition, potential associations between pathohistological findings and hematological parameters are still unclear. We therefore conducted a retrospective analysis of 195 SIV-infected rhesus macaques that were euthanized with AIDS-related symptoms at the German Primate Center, Goettingen, over a 25-year period. Pathological findings were correlated with hematological data. The main findings included myocarditis (12.8 %, endocarditis (9.7 %, and arteriopathy (10.3 % in various organs. Thrombocytopenia occurred more frequently in macaques with endocarditis or arteriopathy than in macaques without CV disease (80 % in animals with endocarditis, 60 % in animals with arteriopathy, p < 0. 0001 and p = 0. 0016, respectively. Further investigations of the interaction between coagulation markers, proinflammatory cytokines, and biomarkers associated with endothelial dysfunction (e.g., D-dimers and histological data (vascular wall structure may unravel the mechanisms underlying HIV/SIV-associated CV comorbidities.

  13. Identification of Unequally Represented Founder Viruses Among Tissues in Very Early SIV Rectal Transmission

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    Jian Chen

    2018-03-01

    Full Text Available Characterizing the transmitted/founder (T/F viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission. We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 104 TCID50 and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA. All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey. Interestingly, our data showed that a cluster of rare T/F viruses was unequally represented in different tissues. This cluster of rare T/F viruses phylogenetically related to the non-dominant SIV variants in the inoculum and was not detected in any rectum tissues, but could be identified in the descending colon, jejunum, spleen, or plasma. In 2 out of 6 macaques, identical SIVmac251 variants belonging to this cluster were detected simultaneously in descending colon/jejunum and the inoculum. We also demonstrated that the average CG dinucleotide frequency of these rare T/F viruses found in tissues, as well as non-dominant variants in the inoculum, was significantly higher than the dominant T/F viruses in tissues and the inoculum. Collectively, these findings suggest that descending colon/jejunum might be more susceptible than rectum to SIV in the very early phase of infection. And host CG suppression, which was previously shown to inhibit HIV replication in vitro, may also contribute to the bottleneck selection during in vivo transmission.

  14. Influence of microwave plasma parameters on light emission from SiV color centers in nanocrystalline diamond films

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    Himics László

    2014-11-01

    Full Text Available Zero phonon line (ZPL shape, position and integral intensity of SiV defect center in diamond is presented for nanocrystalline diamond (NCD films grown at different conditions, NCD films of average grain sizes from ~50 nm up to ~180 nm have been deposited onto c-Si wafer at substrate temperature of 700 and 850oC from mixture with different CH4 and H2 ratios using MWCVD process. Light emission of SiV defect center and Raman scattering properties of NCD samples were measured on a Renishaw micro-Raman spectrometer with 488 nm excitation. Scanning electron microscopy images were used for monitoring surface morphology and for the analysis of the average grain sizes. Sample thickness was determined by in situ laser reflection interferometry. Characteristics of SiV ZPL are discussed in light of the morphology, bonding structure and average grain size of NCD films.

  15. Experimental Oral Herpes Simplex Virus-1 (HSV-1 Co-infection in Simian Immunodeficiency Virus (SIV-Infected Rhesus Macaques

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    Meropi Aravantinou

    2017-12-01

    Full Text Available Herpes simplex virus 1 and 2 (HSV-1/2 similarly initiate infection in mucosal epithelia and establish lifelong neuronal latency. Anogenital HSV-2 infection augments the risk for sexual human immunodeficiency virus (HIV transmission and is associated with higher HIV viral loads. However, whether oral HSV-1 infection contributes to oral HIV susceptibility, viremia, or oral complications of HIV infection is unknown. Appropriate non-human primate (NHP models would facilitate this investigation, yet there are no published studies of HSV-1/SIV co-infection in NHPs. Thus, we performed a pilot study for an oral HSV-1 infection model in SIV-infected rhesus macaques to describe the feasibility of the modeling and resultant immunological changes. Three SIV-infected, clinically healthy macaques became HSV-1-infected by inoculation with 4 × 108 pfu HSV-1 McKrae on buccal, tongue, gingiva, and tonsils after gentle abrasion. HSV-1 DNA was shed in oral swabs for up to 21 days, and shedding recurred in association with intra-oral lesions after periods of no shedding during 56 days of follow up. HSV-1 DNA was detected in explant cultures of trigeminal ganglia collected at euthanasia on day 56. In the macaque with lowest baseline SIV viremia, SIV plasma RNA increased following HSV-1 infection. One macaque exhibited an acute pro-inflammatory response, and all three animals experienced T cell activation and mobilization in blood. However, T cell and antibody responses to HSV-1 were low and atypical. Through rigorous assessesments, this study finds that the virulent HSV-1 strain McKrae resulted in a low level HSV-1 infection that elicited modest immune responses and transiently modulated SIV infection.

  16. Role of Monocyte/Macrophages during HIV/SIV Infection in Adult and Pediatric Acquired Immune Deficiency Syndrome

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    Kristen M. Merino

    2017-12-01

    Full Text Available Monocytes/macrophages are a diverse group of cells that act as first responders in innate immunity and then as mediators for adaptive immunity to help clear infections. In performing these functions, however, the macrophage inflammatory responses can also contribute to pathogenesis. Various monocyte and tissue macrophage subsets have been associated with inflammatory disorders and tissue pathogeneses such as occur during HIV infection. Non-human primate research of simian immunodeficiency virus (SIV has been invaluable in better understanding the pathogenesis of HIV infection. The question of HIV/SIV-infected macrophages serving as a viral reservoir has become significant for achieving a cure. In the rhesus macaque model, SIV-infected macrophages have been shown to promote pathogenesis in several tissues resulting in cardiovascular, metabolic, and neurological diseases. Results from human studies illustrated that alveolar macrophages could be an important HIV reservoir and humanized myeloid-only mice supported productive HIV infection and viral persistence in macrophages during ART treatment. Depletion of CD4+ T cells is considered the primary cause for terminal progression, but it was reported that increasing monocyte turnover was a significantly better predictor in SIV-infected adult macaques. Notably, pediatric cases of HIV/SIV exhibit faster and more severe disease progression than adults, yet neonates have fewer target T cells and generally lack the hallmark CD4+ T cell depletion typical of adult infections. Current data show that the baseline blood monocyte turnover rate was significantly higher in neonatal macaques compared to adults and this remained high with disease progression. In this review, we discuss recent data exploring the contribution of monocytes and macrophages to HIV/SIV infection and progression. Furthermore, we highlight the need to further investigate their role in pediatric cases of infection.

  17. Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2.

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    Bin Jia

    2009-05-01

    Full Text Available Tetherin, also known as BST2, CD317 or HM1.24, was recently identified as an interferon-inducible host-cell factor that interferes with the detachment of virus particles from infected cells. HIV-1 overcomes this restriction by expressing an accessory protein, Vpu, which counteracts tetherin. Since lentiviruses of the SIV(smm/mac/HIV-2 lineage do not have a vpu gene, this activity has likely been assumed by other viral gene products. We found that deletion of the SIV(mac239 nef gene significantly impaired virus release in cells expressing rhesus macaque tetherin. Virus release could be restored by expressing Nef in trans. However, Nef was unable to facilitate virus release in the presence of human tetherin. Conversely, Vpu enhanced virus release in the presence of human tetherin, but not in the presence of rhesus tetherin. In accordance with the species-specificity of Nef in mediating virus release, SIV Nef downregulated cell-surface expression of rhesus tetherin, but did not downregulate human tetherin. The specificity of SIV Nef for rhesus tetherin mapped to four amino acids in the cytoplasmic domain of the molecule that are missing from human tetherin, whereas the specificity of Vpu for human tetherin mapped to amino acid differences in the transmembrane domain. Nef alleles of SIV(smm, HIV-2 and HIV-1 were also able to rescue virus release in the presence of both rhesus macaque and sooty mangabey tetherin, but were generally ineffective against human tetherin. Thus, the ability of Nef to antagonize tetherin from these Old World primates appears to be conserved among the primate lentiviruses. These results identify Nef as the viral gene product of SIV that opposes restriction by tetherin in rhesus macaques and sooty mangabeys, and reveal species-specificity in the activities of both Nef and Vpu in overcoming tetherin in their respective hosts.

  18. Utilizing a TLR5-Adjuvanted Cytomegalovirus as a Lentiviral Vaccine in the Nonhuman Primate Model for AIDS.

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    Jesse D Deere

    Full Text Available Despite tremendous progress in our understanding of human immunodeficiency virus (HIV natural history and advances in HIV treatment, there is neither an approved vaccine nor a cure for infection. Here, we describe the development and characterization of a novel replicating vaccine vector utilizing Cytomegalovirus (CMV and a TLR5 adjuvant. After partial truncation of the central, immunodominant hypervariable domain, flagellin (fliC from Salmonella was cloned downstream of a codon optimized gag gene from simian immunodeficiency virus (SIV and transiently expressed in telomerized rhesus fibroblast (TeloRF cells in culture. Lysates generated from these transfected cells induced the tumor necrosis factor alpha (TNF-α, in a mouse macrophage cell line, in a TLR5-dependent manner. The Gag/FliC expression construct was cloned into a bacterial artificial chromosome encoding the rhesus CMV (RhCMV genome, and infectious RhCMV was generated following transfection of TeloRF cells. This virus stably expressed an SIV Gag/FliC fusion protein through four serial passages. Lysates generated from infected cells induced TNF-α in a TLR5-dependent manner. Western blot analysis of infected cell lysates verified expression of a Gag/FliC fusion protein using a SIV p27 capsid monoclonal antibody. Lastly, rhesus macaques inoculated with this novel RhCMV virus demonstrated increased inflammatory responses at the site of inoculation seven days post-infection when compared to the parental RhCMV. These results demonstrate that an artificially constructed replicating RhCMV expressing an SIV Gag/FliC fusion protein is capable of activating TLR5 in a macrophage cell line in vitro and induction of an altered inflammatory response in vivo. Ongoing animals studies are aimed at determining vaccine efficacy, including subsequent challenge with pathogenic SIV.

  19. Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques

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    Marx Preston

    2006-12-01

    Full Text Available Abstract Background Emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1 is a major obstacle to successful antiretroviral therapy (ART in HIV-infected patients. Whether antiviral immunity can augment ART by suppressing replication of drug-resistant HIV-1 in humans is not well understood, but can be explored in non-human primates infected with simian immunodeficiency virus (SIV. Rhesus macaques infected with live, attenuated SIV develop robust SIV-specific immune responses but remain viremic, often at low levels, for periods of months to years, thus providing a model in which to evaluate the contribution of antiviral immunity to drug efficacy. To investigate the extent to which SIV-specific immune responses augment suppression of drug-resistant SIV, rhesus macaques infected with live, attenuated SIVmac239Δnef were treated with the reverse transcriptase (RT inhibitor tenofovir, and then challenged with pathogenic SIVmac055, which has a five-fold reduced sensitivity to tenofovir. Results Replication of SIVmac055 was detected in untreated macaques infected with SIVmac239Δnef, and in tenofovir-treated, naïve control macaques. The majority of macaques infected with SIVmac055 experienced high levels of plasma viremia, rapid CD4+ T cell loss and clinical disease progression. By comparison, macaques infected with SIVmac239Δnef and treated with tenofovir showed no evidence of replicating SIVmac055 in plasma using allele-specific real-time PCR assays with a limit of sensitivity of 50 SIV RNA copies/ml plasma. These animals remained clinically healthy with stable CD4+ T cell counts during three years of follow-up. Both the tenofovir-treated and untreated macaques infected with SIVmac239Δnef had antibody responses to SIV gp130 and p27 antigens and SIV-specific CD8+ T cell responses prior to SIVmac055 challenge, but only those animals receiving concurrent treatment with tenofovir resisted infection with SIVmac055. Conclusion

  20. Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections.

    Science.gov (United States)

    Asmal, Mohammed; Lane, Sophie; Tian, Meijuan; Nickel, Gabrielle; Venner, Colin; Dirk, Brennan; Dikeakos, Jimmy; Luedemann, Corinne; Mach, Linh; Balachandran, Harikrishnan; Buzby, Adam; Rao, Srinivas; Letvin, Norman; Gao, Yong; Arts, Eric J

    2016-12-01

    For studies on vaccines and therapies for HIV disease, SIV-HIV chimeric viruses harboring the HIV-1 env gene (SHIVenv) remain the best virus in non-human primate models. However, there are still very few SHIVenv viruses that can cause AIDS in non-CD8-depleted animals. In the present study, a recently created CCR5-using SHIVenv_B3 virus with env gene derived from acute/early HIV-1 infections (AHI) successfully established pathogenic infection in macaques. Through a series of investigations on the evolution, mutational profile, and phenotype of the virus and the resultant humoral immune response in infected rhesus macaques, we found that the E32K mutation in the Env C1 domain was associated with macaque pathogenesis, and that the electrostatic interactions in Env may favor E32K at the gp120 N terminus and "lock" the binding to heptad repeat 1 of gp41 in the trimer and produce a SHIVenv with increased fitness and pathogenesis during macaque infections. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV.

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    Jordan Wilkins

    Full Text Available Interferon-induced transmembrane (IFITM proteins are potent antiviral factors shown to restrict the infection of many enveloped viruses, including HIV. Here we report cloning and characterization of a panel of nonhuman primate IFITMs. We show that, similar to human IFITM, nonhuman primate IFITM proteins inhibit HIV and other primate lentiviruses. While some nonhuman primate IFITM proteins are more potent than human counterparts to inhibit HIV-1, they are generally not effective against HIV-2 similar to that of human IFITMs. Notably, depending on SIV strains and also IFITM species tested, nonhuman primate IFITM proteins exhibit distinct activities against SIVs; no correlation was found to support the notion that IFITM proteins are most active in non-natural primate hosts. Consistent with our recent findings for human IFITMs, nonhuman primate IFITM proteins interact with HIV-1 Env and strongly act in viral producer cells to impair viral infectivity and block cell-to-cell transmission. Accordingly, knockdown of primate IFITM3 increases HIV-1 replication in nohuman primate cells. Interestingly, analysis of DNA sequences of human and nonhuman primate IFITMs suggest that IFITM proteins have been undergoing purifying selection, rather than positive selection typical for cellular restriction factors. Overall, our study reveals some new and unexpected features of IFITMs in restricting primate lentiviruses, which enhances our understanding of virus-host interaction and AIDS pathogenesis.

  2. Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV.

    Science.gov (United States)

    Wilkins, Jordan; Zheng, Yi-Min; Yu, Jingyou; Liang, Chen; Liu, Shan-Lu

    2016-01-01

    Interferon-induced transmembrane (IFITM) proteins are potent antiviral factors shown to restrict the infection of many enveloped viruses, including HIV. Here we report cloning and characterization of a panel of nonhuman primate IFITMs. We show that, similar to human IFITM, nonhuman primate IFITM proteins inhibit HIV and other primate lentiviruses. While some nonhuman primate IFITM proteins are more potent than human counterparts to inhibit HIV-1, they are generally not effective against HIV-2 similar to that of human IFITMs. Notably, depending on SIV strains and also IFITM species tested, nonhuman primate IFITM proteins exhibit distinct activities against SIVs; no correlation was found to support the notion that IFITM proteins are most active in non-natural primate hosts. Consistent with our recent findings for human IFITMs, nonhuman primate IFITM proteins interact with HIV-1 Env and strongly act in viral producer cells to impair viral infectivity and block cell-to-cell transmission. Accordingly, knockdown of primate IFITM3 increases HIV-1 replication in nohuman primate cells. Interestingly, analysis of DNA sequences of human and nonhuman primate IFITMs suggest that IFITM proteins have been undergoing purifying selection, rather than positive selection typical for cellular restriction factors. Overall, our study reveals some new and unexpected features of IFITMs in restricting primate lentiviruses, which enhances our understanding of virus-host interaction and AIDS pathogenesis.

  3. Experimental rabies vaccines for humans

    Science.gov (United States)

    McGettigan, James P

    2011-01-01

    Rabies remains a global public health threat that kills more than 55,000 people per year. Rabies disproportionately affects children and, therefore, is ranked the seventh most important infectious disease due to years lost. Prevention of human rabies is accomplished by controlling rabies in domestic and wild animals, including the use of vaccination programs. The usefulness of human rabies vaccines is hampered by high cost, complicated vaccination regimens and lack of compliance, especially in areas of Africa and Asia where human rabies infections are endemic. A single-dose vaccine would greatly benefit efforts to combat this global health threat. However, a single-dose vaccine based on current inactivated vaccines does not appear feasible and other approaches are needed. Technology has advanced since modern human rabies vaccines were developed over 40 years ago. In addition, our understanding of immunological principles that influence the outcome of vaccination has increased. This article describes the current status of inactivated rabies virus vaccines and recent developments arising from the use of reverse genetics technologies designed to develop replication-deficient or single-cycle live rabies virus-based vectors for use as a single-dose rabies vaccine for humans. PMID:20923268

  4. Fowlpoxvirus recombinants coding for the CIITA gene increase the expression of endogenous MHC-II and Fowlpox Gag/Pro and Env SIV transgenes.

    Science.gov (United States)

    Bissa, Massimiliano; Forlani, Greta; Zanotto, Carlo; Tosi, Giovanna; De Giuli Morghen, Carlo; Accolla, Roberto S; Radaelli, Antonia

    2018-01-01

    A complete eradication of an HIV infection has never been achieved by vaccination and the search for new immunogens that can induce long-lasting protective responses is ongoing. Avipoxvirus recombinants are host-restricted for replication to avian species and they do not have the undesired side effects induced by vaccinia recombinants. In particular, Fowlpox (FP) recombinants can express transgenes over long periods and can induce protective immunity in mammals, mainly due to CD4-dependent CD8+ T cells. In this context, the class II transactivator (CIITA) has a pivotal role in triggering the adaptive immune response through induction of the expression of class-II major histocompatibility complex molecule (MHC-II), that can present antigens to CD4+ T helper cells. Here, we report on construction of novel FPgp and FPenv recombinants that express the highly immunogenic SIV Gag-pro and Env structural antigens. Several FP-based recombinants, with single or dual genes, were also developed that express CIITA, driven from H6 or SP promoters. These recombinants were used to infect CEF and Vero cells in vitro and determine transgene expression, which was evaluated by real-time PCR and Western blotting. Subcellular localisation of the different proteins was evaluated by confocal microscopy, whereas HLA-DR or MHC-II expression was measured by flow cytometry. Fowlpox recombinants were also used to infect syngeneic T/SA tumour cells, then injected into Balb/c mice to elicit MHC-II immune response and define the presentation of the SIV transgene products in the presence or absence of FPCIITA. Antibodies to Env were measured by ELISA. Our data show that the H6 promoter was more efficient than SP to drive CIITA expression and that CIITA can enhance the levels of the gag/pro and env gene products only when infection is performed by FP single recombinants. Also, CIITA expression is higher when carried by FP single recombinants than when combined with FPgp or FPenv constructs and can

  5. Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques.

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    Joseph L Mankowski

    Full Text Available Human immunodeficiency virus (HIV infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS disease using a well-characterized simian immunodeficiency (SIV/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5. Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001. Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

  6. Gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic SIV infection.

    Science.gov (United States)

    Glavan, T W; Gaulke, C A; Santos Rocha, C; Sankaran-Walters, S; Hirao, L A; Raffatellu, M; Jiang, G; Bäumler, A J; Goulart, L R; Dandekar, S

    2016-05-01

    HIV targets the gut mucosa early in infection, causing immune and epithelial barrier dysfunction and disease progression. However, gut mucosal sensing and innate immune signaling through mucosal pattern recognition receptors (PRRs) during HIV infection and disease progression are not well defined. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model of AIDS, we found a robust increase in PRRs and inflammatory cytokine gene expression during the acute SIV infection in both peripheral blood and gut mucosa, coinciding with viral replication. PRR expression remained elevated in peripheral blood following the transition to chronic SIV infection. In contrast, massive dampening of PRR expression was detected in the gut mucosa, despite the presence of detectable viral loads. Exceptionally, expression of Toll-like receptor 4 (TLR4) and TLR8 was downmodulated and diverged from expression patterns for most other TLRs in the gut. Decreased mucosal PRR expression was associated with increased abundance of several pathogenic bacterial taxa, including Pasteurellaceae members, Aggregatibacter and Actinobacillus, and Mycoplasmataceae family. Early antiretroviral therapy led to viral suppression but only partial maintenance of gut PRRs and cytokine gene expression. In summary, SIV infection dampens mucosal innate immunity through PRR dysregulation and may promote immune activation, gut microbiota changes, and ineffective viral clearance.

  7. Association of activating KIR copy number variation of NK cells with containment of SIV replication in rhesus monkeys.

    Directory of Open Access Journals (Sweden)

    Ina Hellmann

    2011-12-01

    Full Text Available While the contribution of CD8⁺ cytotoxic T lymphocytes to early containment of HIV-1 spread is well established, a role for NK cells in controlling HIV-1 replication during primary infection has been uncertain. The highly polymorphic family of KIR molecules expressed on NK cells can inhibit or activate these effector cells and might therefore modulate their activity against HIV-1-infected cells. In the present study, we investigated copy number variation in KIR3DH loci encoding the only activating KIR receptor family in rhesus monkeys and its effect on simian immunodeficiency virus (SIV replication during primary infection in rhesus monkeys. We observed an association between copy numbers of KIR3DH genes and control of SIV replication in Mamu-A*01⁻ rhesus monkeys that express restrictive TRIM5 alleles. These findings provide further evidence for an association between NK cells and the early containment of SIV replication, and underscore the potential importance of activating KIRs in stimulating NK cell responses to control SIV spread.

  8. Kunstimuuseumi Kumu püsiväljapanek = Permanent exhibition at the Kumu Art Museum of Estonia

    Index Scriptorium Estoniae

    2007-01-01

    siväljapanekute "Eesti kunsti klassika 18. sajandi algusest kuni 1944. aastani" (kujundus Liina Siib) ja "Eesti kunst 1945-1991" (kujundus Terje Kallast ja Urmas Luure) näitusekujundusest, kujundajatest, nende tähtsamad tööd näituse kujundajatena. 8 värv. vaadet, fotod L. Siibist ja T. Kallastist

  9. CD4 depletion in SIV-infected macaques results in macrophage and microglia infection with rapid turnover of infected cells.

    Directory of Open Access Journals (Sweden)

    Luca Micci

    2014-10-01

    Full Text Available In rhesus macaques (RMs, experimental depletion of CD4+ T-cells prior to SIV infection results in higher viremia and emergence of CD4-independent SIV-envelopes. In this study we used the rhesus recombinant anti-CD4 antibody CD4R1 to deplete RM CD4+ T-cells prior to SIVmac251 infection and investigate the sources of the increased viral burden and the lifespan of productively infected cells. CD4-depleted animals showed (i set-point viral load two-logs higher than controls; (ii macrophages constituting 80% of all SIV vRNA+ cells in lymph node and mucosal tissues; (iii substantial expansion of pro-inflammatory monocytes; (iv aberrant activation and infection of microglial cells; and (v lifespan of productively infected cells significantly longer in comparison to controls, but markedly shorter than previously estimated for macrophages. The net effect of CD4+ T-cell depletion is an inability to control SIV replication and a shift in the tropism of infected cells to macrophages, microglia, and, potentially, other CD4-low cells which all appear to have a shortened in vivo lifespan. We believe these findings have important implications for HIV eradication studies.

  10. DIOS - database of formalized chemotherapeutic regimens.

    Science.gov (United States)

    Klimes, Daniel; Smid, Roman; Kubasek, Miroslav; Vyzula, Rostislav; Dušek, Ladislav

    2013-01-01

    Chemotherapeutic regimens (CHR) and their administration are routine practice in contemporary oncology. The development of a structured, electronic database of standard CHR can help the faster propagation of information about new CHR and at the same time enable assessment of their adherence in clinical practice. The goal was to develop a standardized way to describe a regimen using XML, fill the database with currently available regimens and develop tools to assess the adherence of the treatment to chosen regimen, compare the dose-intensity and recognize the regimen from existing data on drug administration. The data are being inserted in cooperation with expert oncologists and the database currently contains about 260 CHRs. Such system can be used to enhance decision support systems and interoperability of HIS. The database and tools are available online on the internet.

  11. Vaccines (immunizations) - overview

    Science.gov (United States)

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

  12. Ceftiofur hydrochloride affects the humoral and cellular immune response in pigs after vaccination against swine influenza and pseudorabies.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Czyżewska-Dors, Ewelina; Kwit, Krzysztof; Wierzchosławski, Karol; Pejsak, Zygmunt

    2015-10-22

    Cephalosporins are a class of antibiotics that are active against many Gram-positive and some Gram-negative bacteria. Beyond their antibacterial activity, they are reported to have various immunomodulatory properties. It has been shown that they reduce the secretion of cytokines as well as influence the humoral and cellular immune response. In the field conditions antibiotics are frequently administered at the same time as vaccines in pigs and, in the view of their potential immunomodulatory properties, it is important to examine their effect on the development and persistence of the post-vaccinal immune response. Ceftiofur is a very popular veterinary medicine third-generation cephalosporin with a broad spectrum of activity. It has been shown that it can inhibit cytokines secretion and in this way can potentially affect host immune response. The influence of ceftiofur on the immune response has not yet been investigated in pigs. In the present study we evaluated the influence of therapeutic doses of ceftiofur hydrochloride on the post-vaccinal immune response after vaccination with two model vaccines (live and inactivated). Seventy pigs were divided into five groups: control, unvaccinated (C), control vaccinated against swine influenza (SI-V), control vaccinated against pseudorabies (PR-V), vaccinated against SI during ceftiofur administration (SI-CEF) and vaccinated against PR during ceftiofur administration (PR-CEF). Pigs from SICEF and PR-CEF groups received therapeutic dose of ceftiofur for five days. Pigs from SI-CEF, PR-CEF, SIV and PR-V groups were vaccinated against SI and PR. Antibodies to PRV were determined with the use of blocking ELISA tests (IDEXX Laboratories, USA). Humoral responses to SIV were assessed based on haemagglutination inhibition assay. T-cell response was analyzed with the use of proliferation test. The concentrations of IFN- γ and IL-4 in culture supernatant were determined with the use of ELISA kits Invitrogen Corporation, USA). The

  13. Vaccine hesitancy

    Science.gov (United States)

    Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.

    2013-01-01

    Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination. PMID:23584253

  14. Evolving T-cell vaccine strategies for HIV, the virus with a thousand faces

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette [Los Alamos National Laboratory

    2009-01-01

    HIV's rapid global spread and the human suffering it has left in its wake have made AIDS a global heath priority for the 25 years since its discovery. Yet its capacity to rapidly evolve has made combating this virus a tremendous challenge. The obstacles to creating an effective HIV vaccine are formidable, but there are advances in the field on many fronts, in terms of novel vectors, adjuvants, and antigen design strategies. SIV live attenuated vaccine models are able to confer protection against heterologous challenge, and this continues to provide opportunities to explore the biological underpinnings of a protective effect (9). More indirect, but equally important, is new understanding regarding the biology of acute infection (43), the role of immune response in long-term non-progression (6,62, 81), and defining characteristics of broadly neutralizing antibodies (4). In this review we will focus on summarizing strategies directed towards a single issue, that of contending with HIV variation in terms of designing aT-cell vaccine. The strategies that prove most effective in this area can ultimately be combined with the best strategies under development in other areas, with the hope of ultimately converging on a viable vaccine candidate. Only two large HIV vaccine efficacy trials have been completed and both have failed to prevent infection or confer a benefit to infected individual (23,34), but there is ample reason to continue our efforts. A historic breakthrough came in 1996, when it was realized that although the virus could escape from a single antiretroviral (ARV) therapy, it could be thwarted by a combination of medications that simultaneously targeted different parts of the virus (HAART) (38). This revelation came after 15 years of research, thought, and clinical testing; to enable that vital progress the research and clinical communities had to first define and understand, then develop a strategy to counter, the remarkable evolutionary potential of the

  15. Reduction in Rotavirus-associated Acute Gastroenteritis Following Introduction of Rotavirus Vaccine Into Australia's National Childhood Vaccine Schedule

    NARCIS (Netherlands)

    Buttery, Jim P.; Lambert, Stephen B.; Grimwood, Keith; Nissen, Michael D.; Field, Emma J.; Macartney, Kristine K.; Akikusa, Jonathan D.; Kelly, Julian J.; Kirkwood, Carl D.

    Introduction: Rotavirus vaccines were introduced into the funded Australian National Immunization Program (NIP) in July 2007. Due to purchasing arrangements, individual states and territories chose either a 2-dose RV1 (Rotarix, GSK) regimen or 3-dose RV5 (Rotateq, Merck/CSL) regimen. This allowed

  16. Photoluminescence excitation spectroscopy of SiV- and GeV- color center in diamond

    Science.gov (United States)

    Häußler, Stefan; Thiering, Gergő; Dietrich, Andreas; Waasem, Niklas; Teraji, Tokuyuki; Isoya, Junichi; Iwasaki, Takayuki; Hatano, Mutsuko; Jelezko, Fedor; Gali, Adam; Kubanek, Alexander

    2017-06-01

    Color centers in diamond are important quantum emitters for a broad range of applications ranging from quantum sensing to quantum optics. Understanding the internal energy level structure is of fundamental importance for future applications. We experimentally investigate the level structure of an ensemble of few negatively charged silicon-vacancy (SiV-) and germanium-vacancy (GeV-) centers in bulk diamond at room temperature by photoluminescence (PL) and excitation (PLE) spectroscopy over a broad wavelength range from 460 to 650 {nm} and perform power-dependent saturation measurements. For SiV- our experimental results confirm the presence of a higher energy transition at ˜ 2.31 {eV}. By comparison with detailed theoretical simulations of the imaginary dielectric function we interpret the transition as a dipole-allowed transition from {}2{E}g-state to {}2{A}2u-state where the corresponding a 2u -level lies deeply inside the diamond valence band. Therefore, the transition is broadened by the diamond band. At higher excitation power of 10 {mW} we indicate signs of a parity-conserving transition at ˜ 2.03 {eV} supported by saturation measurements. For GeV- we demonstrate that the PLE spectrum is in good agreement with the mirror image of the PL spectrum of the zero-phonon line. Experimentally we do not observe a higher lying energy level up to a transition wavelength of 460 {nm}. The observed PL spectra are identical, independent of excitation wavelength, suggesting a rapid decay to {}2{E}u excited state and followed by optical transition to {}2{E}g ground state. Our investigations convey important insights for future quantum optics and quantum sensing experiments based on SiV--center and GeV--center in diamond.

  17. Gonzalez Regimen (PDQ®)—Patient Version

    Science.gov (United States)

    Expert-reviewed information summary about the Gonzalez regimen as a treatment for people with cancer. Note: The information in this summary is no longer being updated and is provided for reference purposes only.

  18. Measuring turnover of SIV DNA in resting CD4+ T cells using pyrosequencing: implications for the timing of HIV eradication therapies.

    Directory of Open Access Journals (Sweden)

    Jeanette C Reece

    Full Text Available Resting CD4+ T cells are a reservoir of latent HIV-1. Understanding the turnover of HIV DNA in these cells has implications for the development of eradication strategies. Most studies of viral latency focus on viral persistence under antiretroviral therapy (ART. We studied the turnover of SIV DNA resting CD4+ T cells during active infection in a cohort of 20 SIV-infected pigtail macaques. We compared SIV sequences at two Mane-A1*084:01-restricted CTL epitopes using serial plasma RNA and resting CD4+ T cell DNA samples by pyrosequencing, and used a mathematical modeling approach to estimate SIV DNA turnover. We found SIV DNA turnover in resting CD4+ T cells was slow in animals with low chronic viral loads, consistent with the long persistence of latency seen under ART. However, in animals with high levels of chronic viral replication, turnover was high. SIV DNA half-life within resting CD4 cells correleated with viral load (p = 0.0052 at the Gag KP9 CTL epitope. At a second CTL epitope in Tat (KVA10 there was a trend towards an association of SIV DNA half-life in resting CD4 cells and viral load (p = 0.0971. Further, we found that the turnover of resting CD4+ T cell SIV DNA was higher for escape during early infection than for escape later in infection (p = 0.0084. Our results suggest viral DNA within resting CD4 T cells is more labile and may be more susceptible to reactivation/eradication treatments when there are higher levels of virus replication and during early/acute infection.

  19. Compartmentalization of SIV Replication Within Secondary Lymphoid Tissues of Rhesus Macaques is Linked to Disease Stage and Inversely Related to Localization of Virus-Specific CTL1 2

    Science.gov (United States)

    Connick, Elizabeth; Folkvord, Joy M.; Lind, Katherine T.; Rakasz, Eva G.; Miles, Brodie; Wilson, Nancy A.; Santiago, Mario L.; Schmitt, Kimberly; Stephens, Edward B.; Kim, Hyeon O.; Wagstaff, Reece; Li, Shengbin; Abdelaal, Hadia M.; Kemp, Nathan; Watkins, David I.; MaWhinney, Samantha; Skinner, Pamela J.

    2014-01-01

    We previously demonstrated that HIV replication is concentrated in lymph node B cell follicles during chronic infection and that HIV-specific CTL fail to accumulate in large numbers at those sites. It is unknown whether these observations can be generalized to other secondary lymphoid tissues, or whether virus compartmentalization occurs in the absence of CTL. We evaluated these questions in SIVmac239-infected rhesus macaques by quantifying SIV RNA+ cells and SIV-specific CTL in situ in spleen, lymph nodes and intestinal tissues obtained at several stages of infection. During chronic asymptomatic infection prior to simian AIDS (SAIDS), SIV-producing cells were more concentrated in follicular compared to extrafollicular regions of secondary lymphoid tissues. At day 14 of infection, when CTL have minimal impact on virus replication, there was no compartmentalization of SIV-producing cells. Virus compartmentalization was diminished in animals with SAIDS, which often have low frequency CTL responses. SIV-specific CTL were consistently more concentrated within extrafollicular regions of lymph node and spleen in chronically infected animals regardless of epitope specificity. Frequencies of SIV-specific CTL within follicular and extrafollicular compartments predicted SIV RNA+ cells within these compartments in a mixed model. Few SIV-specific CTL expressed the follicular homing molecule CXCR5 in the absence of the extrafollicular retention molecule CCR7, possibly accounting for the paucity of follicular CTL. These findings bolster the hypothesis that B cell follicles are immune privileged sites and suggest that strategies to augment CTL in B cell follicles could lead to improved viral control and possibly a functional cure for HIV infection. PMID:25362178

  20. Progress in Brucella vaccine development

    Science.gov (United States)

    YANG, Xinghong; SKYBERG, Jerod A.; CAO, Ling; CLAPP, Beata; THORNBURG, Theresa; PASCUAL, David W.

    2012-01-01

    Brucella spp. are zoonotic, facultative intracellular pathogens, which cause animal and human disease. Animal disease results in abortion of fetuses; in humans, it manifests flu-like symptoms with an undulant fever, with osteoarthritis as a common complication of infection. Antibiotic regimens for human brucellosis patients may last several months and are not always completely effective. While there are no vaccines for humans, several licensed live Brucella vaccines are available for use in livestock. The performance of these animal vaccines is dependent upon the host species, dose, and route of immunization. Newly engineered live vaccines, lacking well-defined virulence factors, retain low residual virulence, are highly protective, and may someday replace currently used animal vaccines. These also have possible human applications. Moreover, due to their enhanced safety and efficacy in animal models, subunit vaccines for brucellosis show great promise for their application in livestock and humans. This review summarizes the progress of brucellosis vaccine development and presents an overview of candidate vaccines. PMID:23730309

  1. Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load.

    Directory of Open Access Journals (Sweden)

    Collin R Diedrich

    2010-03-01

    Full Text Available HIV-infected individuals with latent Mycobacterium tuberculosis (Mtb infection are at significantly greater risk of reactivation tuberculosis (TB than HIV-negative individuals with latent TB, even while CD4 T cell numbers are well preserved. Factors underlying high rates of reactivation are poorly understood and investigative tools are limited. We used cynomolgus macaques with latent TB co-infected with SIVmac251 to develop the first animal model of reactivated TB in HIV-infected humans to better explore these factors. All latent animals developed reactivated TB following SIV infection, with a variable time to reactivation (up to 11 months post-SIV. Reactivation was independent of virus load but correlated with depletion of peripheral T cells during acute SIV infection. Animals experiencing reactivation early after SIV infection (<17 weeks had fewer CD4 T cells in the periphery and airways than animals reactivating in later phases of SIV infection. Co-infected animals had fewer T cells in involved lungs than SIV-negative animals with active TB despite similar T cell numbers in draining lymph nodes. Granulomas from these animals demonstrated histopathologic characteristics consistent with a chronically active disease process. These results suggest initial T cell depletion may strongly influence outcomes of HIV-Mtb co-infection.

  2. The dog that did not bark: malaria vaccines without antibodies.

    NARCIS (Netherlands)

    Heppner, D.G.; Schwenk, R.J.; Arnot, D.; Sauerwein, R.W.; Luty, A.J.F.

    2007-01-01

    To date, the only pre-blood stage vaccine to confer protection against malaria in field trials elicits both antigen-specific antibody and T-cell responses. Recent clinical trials of new heterologous prime-boost malaria vaccine regimens using DNA, fowlpox or MVA, have chiefly elicited T-cell

  3. Green revolution vaccines, edible vaccines

    African Journals Online (AJOL)

    Admin

    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 pathogen for which the immune system has been primed (Arntzen, 1997). The release of vaccine is.

  4. Leptospirosis vaccines

    Directory of Open Access Journals (Sweden)

    Jin Li

    2007-12-01

    Full Text Available Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP vaccines, lipopolysaccharide (LPS vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.

  5. Polio Vaccine

    Science.gov (United States)

    ... IBS) Home Family Health Infants and Toddlers Polio Vaccine Polio Vaccine Share Print What is polio? Poliomyelitis (polio) is ... each year. Fortunately, the use of the polio vaccine has made the disease very rare in most ...

  6. Measles Vaccination

    Science.gov (United States)

    ... World Health Organization Pan American Health Organization Measles Vaccination Pronounced (MEE-zills) Recommend on Facebook Tweet Share ... also be up to date on their MMR vaccination. The MMR vaccine is very safe and effective. ...

  7. Avian influenza in ovo vaccination with replication defective recombinant adenovirus in chickens: Vaccine potency, antibody persistence, and maternal antibody transfer

    Science.gov (United States)

    Protective immunity against avian influenza (AI) can be elicited in chickens in a single-dose regimen by in ovo vaccination with a replication-competent adenovirus (RCA)-free human adenovirus serotype 5 (Ad)-vector encoding the AI virus (AIV) hemagglutinin (HA). We evaluated vaccine potency, antibo...

  8. Use of the nonavalent HPV vaccine in individuals previously fully or partially vaccinated with bivalent or quadrivalent HPV vaccines

    DEFF Research Database (Denmark)

    Van Damme, Pierre; Bonanni, Paolo; Bosch, F Xavier

    2016-01-01

    With the availability of the nonavalent human papillomavirus (HPV) vaccine, vaccinees, parents and healthcare providers need guidance on how to complete an immunization course started with the bi- or quadrivalent vaccine and whether to revaccinate individuals who have completed a full immunization...... course with the bi- or quadrivalent vaccine. To answer these questions three parameters should be considered: age at the start of vaccination (9 to 14 years of age versus 15 years and older, the cut-off for 2 or 3 doses schedule), the number of doses already received and the time interval between doses....... Based on a number of scenarios, we propose that the 9-valent vaccine can be used to complete an incomplete vaccination regimen or might be added to a previous completed schedule to extend protection....

  9. Functional Performance Evaluation of the Northwestern University Flexible Subischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral Amputation

    Science.gov (United States)

    2016-10-01

    Socket for Persons with Transfemoral Amputation PRINCIPAL INVESTIGATOR: Dr. Stefania Fatone, PhD CONTRACTING ORGANIZATION: Northwestern...University Flexible Subischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral Amputation 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1...0708 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Stefania Fatone, PhD 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: s-fatone@northwestern.edu 5f. WORK

  10. Transcription Profiling Reveals Potential Mechanisms of Dysbiosis in the Oral Microbiome of Rhesus Macaques with Chronic Untreated SIV Infection

    Science.gov (United States)

    Ocon, Susan; Murphy, Christina; Dang, Angeline T.; Sankaran-Walters, Sumathi; Li, Chin-Shang; Tarara, Ross; Borujerdpur, Niku; Dandekar, Satya; Paster, Bruce J.; George, Michael D.

    2013-01-01

    A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and “macaque versions” of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides. PMID:24312248

  11. An accelerated rabies vaccine schedule based on toll-like receptor 3 (TLR3) agonist PIKA adjuvant augments rabies virus specific antibody and T cell response in healthy adult volunteers.

    Science.gov (United States)

    Wijaya, Limin; Tham, Christine Y L; Chan, Yvonne F Z; Wong, Abigail W L; Li, L T; Wang, Lin-Fa; Bertoletti, Antonio; Low, Jenny G

    2017-02-22

    Rabies is a fatal disease where post-exposure prophylaxis (PEP) is crucial in preventing infection. However, deaths even after appropriate PEP, have been reported. The PIKA Rabies vaccine adjuvant is a TLR3 agonist that activates B and T cells leading to a robust immune response. We conducted a phase I, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA Rabies vaccine and an accelerated vaccine regimen. Thirty-seven subjects were randomized into 3 groups: control vaccine classic regimen, PIKA vaccine classic regimen and PIKA vaccine accelerated regimen. Subjects were followed up for safety, rabies virus neutralizing antibodies (RVNA) and T cell responses. Both the control and PIKA Rabies vaccine were well tolerated. All adverse events (AEs) were mild and self-limiting. Seventy-five percent of subjects in the PIKA accelerated regimen achieved a RVNA titer ⩾0.5IU/mL on day 7, compared to 53.9% in the PIKA classic regimen (p=0.411) and 16.7% in control vaccine classic regimen (p=0.012). The PIKA rabies vaccine elicited multi-specific rabies CD4 mediated T cell response already detectable ex vivo at day 7 after vaccination and that was maintained at day 42. The investigational PIKA rabies vaccine was well tolerated and more immunogenic than the commercially available vaccine in healthy adults. Clinical trial registry: The study was registered with clinicaltrials.gov NCT02657161. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. DNA Vaccines

    Indian Academy of Sciences (India)

    DNA vaccine, immune response, antibodies, infectious diseases. GENERAL I ARTICLE. DNA Vaccines. P N Rangarajan. History of Vaccine Development. The year 1996 marked the 200th anniversary of the first vaccine developed against smallpox by Edward Jenner. In the now- famous 1796 experiment, Jenner scratched ...

  13. Vaccination, seizures and 'vaccine damage'.

    Science.gov (United States)

    Brown, Natasha J; Berkovic, Samuel F; Scheffer, Ingrid E

    2007-04-01

    Concerns about the safety of vaccination have plagued the community, with reduction in vaccine uptake resulting in increased risk of epidemics. Vaccination has been implicated in the cause of febrile seizures, 'vaccine encephalopathy' and autistic spectrum disorders. Evaluation of alleged associations is complicated by evolution in the vaccination field. This review focuses on the risk of seizures following vaccination and the alleged associations of vaccination with vaccine encephalopathy and also with autism spectrum disorders. Over the last decade the introduction of new vaccines such as the acellular pertussis vaccine has produced a reduction in seizures following vaccination, the outcome of which was benign even with older vaccines. New evidence emerged in 2006 showing that cases of alleged 'vaccine encephalopathy' are due to mutations within a sodium channel gene. The weight of epidemiological evidence does not support a relationship between vaccination and childhood epileptic encephalopathies or autism spectrum disorders. Vaccines are safer than ever before, but the challenge remains to convey this message to society in such a way that produces change in attitudes to vaccination and subsequent increase in vaccine coverage.

  14. Imaging lymphoid tissues in nonhuman primates to understand SIV pathogenesis and persistence.

    Science.gov (United States)

    Deleage, Claire; Turkbey, Baris; Estes, Jacob D

    2016-08-01

    CD4+ T cells are the primary HIV-1 target cell, with the vast majority of these cells residing within lymphoid tissue compartments throughout the body. Predictably, HIV-1 infection, replication, localization, reservoir establishment and persistence, as well as associated host immune and inflammatory responses and disease pathology principally take place within the tissues of the immune system. By virture of the fact that the virus-host struggle is played out within lymphoid and additional tissues compartments in HIV-1 infected individuals it is critical to understand HIV-1 infection and disease within these relevant tissue sites; however, there are obvious limitations to studying these dynamic processes in humans. Nonhuman primate (NHP) research has provided a vital bridge between basic and preclinical research and clinical studies, with experimental SIV infection of NHP models offering unique opportunities to understand key processes of HIV-1 infection and disease that are either not practically feasible or ethical in HIV-1 infected humans. In this review we will discuss current approaches to studying the tissue based immunopathogenesis of AIDS virus infection in NHPs, including both analyses of tissues obtained at biopsy or necropsy and complementary non-invasive imaging approaches that may have practical utility in monitoring HIV-1 disease in the clinical setting. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. DNA VACCINES

    OpenAIRE

    Aksu, Burak

    2016-01-01

    Traditionally, protection against infectious diseases has relied on the use of attenuated or killed vaccines. However, many such vaccines are inadequate for reason of efficacy, safety, and cost effectiveness. Live-attenuated vaccines may be immunosuppressive, cause disease if not attenuated sufficiently, or provide limited immunity if too much attenuated. A major concern regarding the use of live vaccines is the possibility of outgrowth of more virulent organisms. Killed vaccines are often un...

  16. Hepatitis Vaccines

    OpenAIRE

    Sina Ogholikhan; Kathleen B. Schwarz

    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 ...

  17. Safety of specific immunotherapy using an ultra-rush induction regimen in bee and wasp allergy.

    Science.gov (United States)

    Bożek, Andrzej; Kołodziejczyk, Krzysztof

    2018-02-01

    Specific allergen immunotherapy to Hymenoptera venom (VIT) is a basic treatment for patients allergic to Hymenoptera venom. The aim of the study was to evaluate the safety of an ultra-rush regimen compared with the rush and conventional protocols. In 31 patients with an allergy to bee venom and 82 with an allergy to wasp venom, the allergic adverse reactions during VIT were monitored. Patients were selected based on the criteria established by EAACI (European Academy of Allergy and Clinical Immunology) recommendations. Adverse reactions during the ultra-rush immunotherapy were measured, documented and classified according to the criteria of Mueller. Ultra-rush, rush or conventional protocols of the initial phase VIT using the Venomenhal vaccine (Hal Allergy, Leiden, Netherlands) were conducted. Six (13.7%) patients on the ultra-rush regimen, 5 (14.3%) patients on the rush regimen and 9 (26.5%) on conventional VIT experienced an allergic reaction. There were no associations between the adverse allergic reactions and the following factors: gender, total IgE and allergen-specific IgE to wasp or bee venom before the VIT and cardiological drugs that were used. We found that the ultra-rush protocol (similar to the rush protocol) using the Venomenhal vaccine is safer than the conventional protocol.

  18. Three-year duration of immunity in cats vaccinated with a canarypox-vectored recombinant rabies virus vaccine.

    Science.gov (United States)

    Jas, D; Coupier, C; Toulemonde, C Edlund; Guigal, P-M; Poulet, H

    2012-11-19

    Despite the availability of efficacious vaccines for animals and humans, rabies is still a major zoonosis. Prevention of rabies in dogs and cats is key for reducing the risk of transmission of this deadly disease to humans. Most veterinary vaccines are adjuvanted inactivated vaccines and have been shown to provide one to four-year duration of immunity. In response to debates about the safety of adjuvanted vaccines in cats, a non-adjuvanted feline rabies vaccine with one-year duration of immunity claim was specifically developed using the canarypoxvirus vector technology. The objective of this study was to validate a vaccination program based on primary vaccination, revaccination one year later and boosters every three years. Seronegative cats were vaccinated at 12 weeks of age and received a booster vaccination one year later. This vaccination regimen induced a strong and sustained antibody response, and all vaccinated animals were protected against virulent rabies challenge carried out 3 years after vaccination. These results validated 3-year duration of immunity after a complete basic vaccination program consisting in primary vaccination from 12 weeks of age followed by revaccination one year later with a non-adjuvanted canarypox-vectored vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. CTLA-4+PD-1-Memory CD4+T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques.

    Science.gov (United States)

    McGary, Colleen S; Deleage, Claire; Harper, Justin; Micci, Luca; Ribeiro, Susan P; Paganini, Sara; Kuri-Cervantes, Leticia; Benne, Clarisse; Ryan, Emily S; Balderas, Robert; Jean, Sherrie; Easley, Kirk; Marconi, Vincent; Silvestri, Guido; Estes, Jacob D; Sekaly, Rafick-Pierre; Paiardini, Mirko

    2017-10-17

    Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals but does not eliminate the reservoir of latently infected cells. Recent work identified PD-1 + follicular helper T (Tfh) cells as an important cellular compartment for viral persistence. Here, using ART-treated, SIV-infected rhesus macaques, we show that CTLA-4 + PD-1 - memory CD4 + T cells, which share phenotypic markers with regulatory T cells, were enriched in SIV DNA in blood, lymph nodes (LN), spleen, and gut, and contained replication-competent and infectious virus. In contrast to PD-1 + Tfh cells, SIV-enriched CTLA-4 + PD-1 - CD4 + T cells were found outside the B cell follicle of the LN, predicted the size of the persistent viral reservoir during ART, and significantly increased their contribution to the SIV reservoir with prolonged ART-mediated viral suppression. We have shown that CTLA-4 + PD-1 - memory CD4 + T cells are a previously unrecognized component of the SIV and HIV reservoir that should be therapeutically targeted for a functional HIV-1 cure. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL-21.

    Directory of Open Access Journals (Sweden)

    Suresh Pallikkuth

    Full Text Available In pathogenic HIV and SIV infections of humans and rhesus macaques (RMs, preferential depletion of CD4⁺ Th17 cells correlates with mucosal immune dysfunction and disease progression. Interleukin (IL-21 promotes differentiation of Th17 cells, long-term maintenance of functional CD8⁺ T cells, and differentiation of memory B cells and antibody-secreting plasma cells. We hypothesized that administration of IL-21 will improve mucosal function in the context of pathogenic HIV/SIV infections. To test this hypothesis, we infected 12 RMs with SIV(mac239 and at day 14 post-infection treated six of them with rhesus rIL-21-IgFc. IL-21-treatment was safe and did not increase plasma viral load or systemic immune activation. Compared to untreated animals, IL-21-treated RMs showed (i higher expression of perforin and granzyme B in total and SIV-specific CD8⁺ T cells and (ii higher levels of intestinal Th17 cells. Remarkably, increased levels of Th17 cells were associated with reduced levels of intestinal T cell proliferation, microbial translocation and systemic activation/inflammation in the chronic infection. In conclusion, IL-21-treatment in SIV-infected RMs improved mucosal immune function through enhanced preservation of Th17 cells. Further preclinical studies of IL-21 may be warranted to test its potential use during chronic infection in conjunction with antiretroviral therapy.

  1. Occurrence and severity of lung lesions in slaughter pigs vaccinated against Mycoplasma hyopneumoniae with different strategies.

    Science.gov (United States)

    Hillen, Sonja; von Berg, Stephan; Köhler, Kernt; Reinacher, Manfred; Willems, Hermann; Reiner, Gerald

    2014-03-01

    Different vaccination strategies against Mycoplasma hyopneumoniae have been adopted worldwide. Reports from the field indicate varying levels of protection among currently available vaccines. The goal of the present study was to compare the efficacies of three widespread commercial vaccination strategies against M. hyopneumoniae under field conditions. 20 farms were included. 14 farms used different single dose vaccines (vaccine 1 [V1], 8 herds; vaccine 2 [V2], 6 herds); another 6 farms (V3) used a two dose vaccination strategy. Gross lesions of 854 lungs and histopathology from 140 lungs were quantified, and a quantitative PCR was applied to detect M. hyopneumoniae and porcine circovirus 2 (PCV2) DNA in lung tissue (n=140). In addition, porcine reproductive and respiratory disease virus (PRRSV), swine influenza virus (SIV), Actinobacillus pleuropneumoniae, Haemophilus parasuis and Pasteurella multocida were tested by qualitative PCR. 53% of lungs were positive for M. hyopneumoniae. 55.9% of lungs showed macroscopic enzootic pneumonia (EP)-like lesions. Lung lesion scores (Phyopneumoniae-loads (Phyopneumoniae indicating that the applied diagnostic tools are valuable in confirming the prevalence and severity of M. hyopneumoniae infections. Comparing different vaccination strategies against M. hyopneumoniae indicates varying levels of protection. M. hyopneumoniae is still a major problem despite the widely applied vaccination. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. 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.

  3. DENGUE VACCINES.

    Science.gov (United States)

    Thisyakorn, Usa; Thisyakorn, Chule

    2015-01-01

    The uniqueness of the dengue viruses (DENVs) and the spectrum of disease resulting from infection have made dengue vaccine development difficult. Several vaccine candidates are currently being evaluated in clinical studies. The candidate currently at the most advanced clinical development stage, a live-attenuated tetravalent vaccine based on the chimeric yellow fever-dengue virus (CYD-TDV), has progressed to Phase 3 efficacy studies. Several other live-attenuated vaccines, as well as subunit, DNA, and purified inactivated vaccine candidates are at earlier stages of clinical development. Additional technological approaches, such as virus-vectored and Virus-Like Particles (VLP)-based vaccines are under evaluation in preclinical studies.

  4. Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms for HIV-1 Prevention: A Randomized Trial

    Science.gov (United States)

    Baden, Lindsey R; Karita, Etienne; Mutua, Gaudensia; Bekker, Linda-Gail; Gray, Glenda; Page-Shipp, Liesl; Walsh, Stephen R; Nyombayire, Julien; Anzala, Omu; Roux, Surita; Laher, Fatima; Innes, Craig; Seaman, Michael; Cohen, Yehuda Z; Peter, Lauren; Frahm, Nicole; McElrath, M Juliana; Hayes, Peter; Swann, Edith; Grunenberg, Nicole; Grazia-Pau, Maria; Weijtens, Mo; Sadoff, Jerry; Dally, Len; Lombardo, Angela; Gilmour, Jill; Cox, Josephine; Dolin, Raphael; Fast, Patricia; Barouch, Dan H; Laufer, Dagna S; Johnson, Jennifer; Kleinjan, Jane; Ingabire, Rosine; Nyasani, Delvin; Crida, Danielle; Mangeya, Nicholas; Mamba, Musawenkosi; Mngadi, Kathy; Dominguez, David J; Yanosick, Katherine E; Cormier, Emmanuel; Hural, John; Stevens, Gwynn; Adams, Elizabeth; Kublin, James; Hendriks, Jenny; Sayeed, Eddy; Ackland, James; Anas, Kamaal; Zackariah, Devika; Vooijs, Dani; Chinyenze, Kundai; Matsoso, Mabela; Park, Harriet; Welsh, Sabrina

    2016-01-01

    Background A prophylactic HIV-1 vaccine is a global health priority. Objective To assess a novel vaccine platform as a prophylactic HIV-1 vaccine regimen. Design/Setting This randomized, double-blind, placebo-controlled trial assessed two candidate HIV-1 vaccines (Ad26.EnvA and Ad35-Env both at 5×1010 vp) in homologous and heterologous combinations in three geographic regions (US, East and South Africa). Both subjects and study personnel were blinded to treatment allocation. (NCT 01215149). Patients Healthy HIV uninfected adults. Measurements Safety and immunogenicity were assessed and the impact of baseline vector immunity was analyzed. Results 217 subjects received at least 1 vaccination and 210 (>96%) completed follow-up, No vaccine-associated serious adverse events occurred. All regimens were generally well tolerated though more vaccine recipients had transient moderate or severe systemic reactions (36.5%) compared to placebo recipients (20.5%). All regimens elicited humoral and cellular immune responses in nearly all volunteers. There was no impact of pre-existing Ad26 or Ad35 neutralizing antibody titers on vaccine safety and little on immunogenicity. In both homologous and heterologous regimens the second vaccination significantly increased EnvA antibody titers (~20 fold from median ELISA titers of 30–300 to 3000). The heterologous regimen Ad26-Ad35 elicited significantly higher EnvA antibody titers than Ad35-Ad26. T cell responses were modest and lower in East Africa than in South Africa and the United States. Conclusions Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not have a significant impact on immune responses. Second vaccinations in all regimens significantly boosted EnvA titers though vaccine order in the heterologous regimen had a modest effect on the immune response. Primary Funding IAVI, NIAID/NIH, and the Ragon Institute in collaboration with Crucell Holland BV. PMID:26833336

  5. Immune targeting of PD-1{sup hi} expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Vargas-Inchaustegui, Diego A.; Xiao, Peng; Hogg, Alison E.; Demberg, Thorsten; McKinnon, Katherine [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Venzon, David [Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Brocca-Cofano, Egidio; DiPasquale, Janet [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Lee, Eun M.; Hudacik, Lauren; Pal, Ranajit [Advanced Bioscience Laboratories Inc., Rockville, MD 20850 (United States); Sui, Yongjun; Berzofsky, Jay A. [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Liu, Linda; Langermann, Solomon [Amplimmune Inc., Gaithersburg, MD 20878 (United States); Robert-Guroff, Marjorie, E-mail: guroffm@mail.nih.gov [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-12-15

    High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function. We evaluated the phenotype and distribution of T cells and Tregs during antiretroviral therapy plus PD-1 modulation (using a B7-DC-Ig fusion protein) and post-ART. Chronically SIV-infected rhesus macaques received: 11 weeks of ART (Group A); 11 weeks of ART plus B7-DC-Ig (Group B); 11 weeks of ART plus B7-DC-Ig, then 12 weeks of B7-DC-Ig alone (Group C). Continuous B7-DC-Ig treatment (Group C) decreased rebound viremia post-ART compared to pre-ART levels, associated with decreased PD-1{sup hi} expressing T cells and Tregs in PBMCs, and PD-1{sup hi} Tregs in lymph nodes. It transiently decreased expression of Ki67 and α{sub 4}β{sub 7} in PBMC CD4{sup +} and CD8{sup +} Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1{sup hi} cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses. - Highlights: • B7-DC-Ig modulates PD-1{sup hi} cells in SIV-infected rhesus macaques during and post-ART. • Continued PD-1 modulation post-ART maintains PD-1{sup hi} cells at low levels. • Continued PD-1 modulation post-ART maintains a favorable T cell and Treg repertoire.

  6. Spatially controlled fabrication of a bright fluorescent nanodiamond-array with enhanced far-red Si-V luminescence

    International Nuclear Information System (INIS)

    Singh, Sonal; Thomas, Vinoy; Kharlampieva, Eugenia; Catledge, Shane A; Martyshkin, Dmitry; Kozlovskaya, Veronika

    2014-01-01

    We demonstrate a novel approach to precisely pattern fluorescent nanodiamond-arrays with enhanced far-red intense photostable luminescence from silicon-vacancy (Si-V) defect centers. The precision-patterned pre-growth seeding of nanodiamonds is achieved by a scanning probe ‘dip-pen’ nanolithography technique using electrostatically driven transfer of nanodiamonds from ‘inked’ cantilevers to a UV-treated hydrophilic SiO 2 substrate. The enhanced emission from nanodiamond dots in the far-red is achieved by incorporating Si-V defect centers in a subsequent chemical vapor deposition treatment. The development of a suitable nanodiamond ink and mechanism of ink transport, and the effect of humidity and dwell time on nanodiamond patterning are investigated. The precision patterning of as-printed (pre-CVD) arrays with dot diameter and dot height as small as 735 nm ± 27 nm and 61 nm ± 3 nm, respectively, and CVD-treated fluorescent ND-arrays with consistently patterned dots having diameter and height as small as 820 nm ± 20 nm and, 245 nm ± 23 nm, respectively, using 1 s dwell time and 30% RH is successfully achieved. We anticipate that the far-red intense photostable luminescence (∼738 nm) observed from Si-V defect centers integrated in spatially arranged nanodiamonds could be beneficial for the development of next generation fluorescence-based devices and applications. (paper)

  7. [ADOC regimen for unresectable advanced thymic cancer].

    Science.gov (United States)

    Koizumi, T; Takabayashi, Y; Yamagishi, S; Tsushima, K; Takamizawa, A; Takashi, S; Tsukadaira, A; Masubuchi, T; Yamamoto, H; Kaneki, T; Yamaguchi, S; Hachiya, T; Hayasaka, M; Fujimoto, K; Kubo, K

    1999-12-01

    Between 1996 and 1998, we treated 6 patients with unresectable and advanced thymic cancer (stages IVa and IVb). All received 50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously (i.v.) on day 1,0.6 mg/m2 of vincristine i.v. on day 3, and 700 mg/m2 of cyclophosphamide i.v. on day 4; ADOC regimen, respectively at 3-4 week intervals. Four patients obtained a partial response (PR) after ADOC chemotherapy and the overall clinical response rate was 67%. No life-threatening side effects were noted. In 2 patients, cisplatin plus VP-16 chemotherapy failed to demonstrate any benefits prior to the ADOC regimen. Radiotherapy was initiated after the achievement of PR in the other 2 patients. ADOC chemotherapy appears to be an effective treatment for thymic cancer.

  8. Evaluation of rabies immunogenicity and tolerability following a purified chick embryo cell rabies vaccine administered concomitantly with a Japanese encephalitis vaccine.

    Science.gov (United States)

    Jelinek, Tomas; Cramer, Jakob P; Dieckmann, Sebastian; Hatz, Christoph; Paulke-Korinek, Maria; Alberer, Martin; Reisinger, Emil C; Costantini, Marco; Gniel, Dieter; Bosse, Dietrich; Lattanzi, Maria

    2015-01-01

    For individuals traveling at short notice to rabies and Japanese encephalitis (JE) endemic countries, concomitant administration of travel vaccines within a short period is often required. The aim of this study was to determine whether an accelerated (one-week: Days 1-8) pre-exposure rabies (Rabipur(®), Novartis Vaccines) vaccination regimen administered concomitantly with a Japanese encephalitis (JE) vaccination (Ixiaro(®), Valneva) regimen, is non-inferior to the standard (four-week: Days 1, 8, 29) rabies regimen administered alone or concomitantly with the JE vaccine. Healthy adults (18 to ≤ 65 years) were randomized into Rabies + JE-Standard, Rabies + JE-Accelerated, Rabies-Standard and JE-Standard groups. Relative immunogenicity for rabies in each regimen was assessed using the rapid fluorescent focus inhibition test. Safety was evaluated up to and including Day 57. Non-inferior immunogenicity for rabies was established between the Rabies + JE-Accelerated group compared to both the Rabies-Standard and Rabies + JE-Standard groups; as well as between the Rabies + JE-Standard regimen and the Rabies-Standard regimen. By Day 57, adequate neutralizing levels were achieved by 97-100% of subjects across all groups. Adverse events (AEs) were comparable for all groups. An accelerated pre-exposure rabies and JE vaccination regimen is non-inferior to the standard four-week rabies regimen and may thus provide a more convenient regimen for individuals traveling to endemic countries at short notice. NCT01662440. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. New Treatment Regimen for Latent Tuberculosis Infection

    Centers for Disease Control (CDC) Podcasts

    2012-03-15

    In this podcast, Dr. Kenneth Castro, Director of the Division of Tuberculosis Elimination, discusses the December 9, 2011 CDC guidelines for the use of a new regimen for the treatment of persons with latent tuberculosis infection.  Created: 3/15/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 3/15/2012.

  10. Anthrax Vaccine

    Science.gov (United States)

    ... anthrax vaccine causes long-term health problems.Independent civilian committees have not found anthrax vaccination to be ... doctor, or get the person to a doctor right away. Tell your doctor what happened, the date ...

  11. Vaccine Safety

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Vaccine Safety Note: Javascript is disabled or is not ... CDC.gov . Recommend on Facebook Tweet Share Compartir Vaccine Adverse Events Reporting System (VAERS) New website and ...

  12. Vaccine Finder

    Science.gov (United States)

    ... list . Showing availability for 6,604 locations. Influenza Vaccine Recommended for everyone greater than or equal to ... which one may be right for you! Flu Vaccines Protects again influenza, commonly called flu, a respiratory ...

  13. Decreased number of CD4+ and CD8+ T cells that express the interleukin-7 receptor in blood and tissues of SIV-infected macaques

    International Nuclear Information System (INIS)

    Moniuszko, Marcin; Edghill-Smith, Yvette; Venzon, David; Stevceva, Liljana; Nacsa, Janos; Tryniszewska, Elzbieta; Tsai, Wen-Po; Franchini, Genoveffa

    2006-01-01

    Acute HIV/SIV (human/simian immunodeficiency virus) infection results in severe CD4 + T cell depletion in lymphoid compartments. During the chronic phase of infection, CD4 + T cell numbers rebound in blood but remain low in the gut-associated lymphoid tissue (GALT), even when viral replication is suppressed by antiretroviral therapy (ART). Thus, strategies to repopulate lymphoid compartments may ameliorate the clinical outcome of HIV/SIV infection. Interleukin (IL)-7 is a key cytokine for the maintenance of homeostatic proliferation of T cells. In HIV/SIV infection, IL-7 expression is increased, likely to compensate for T cell loss, suggesting that supraphysiological administration of IL-7 could provide additional benefit. However, the ability of T cells to respond to IL-7 is dependent on the level of expression of the IL-7 receptor (IL-7R) in T cells in various body compartments. In here, we investigated the proportion of IL-7R + T cells in blood, spleen, gut, and genitourinary tract of healthy and SIV-infected macaques with various degrees of CD4 + T cell depletion. We found that the percentage of T cells expressing IL-7R was significantly lower in both CD4 + and CD8 + T cell subsets in SIV-infected macaques than in healthy animals and this decrease directly correlated with the CD4 + T cell number. Importantly, the proportion of CD4 + and CD8 + T cells expressing IL-7R in blood paralleled that found in tissues. IL-7R + T cells within the SIV-specific CD8 + T cells varied and were lowest in most tissues of viremic macaques, likely reflecting continuous antigen stimulation of effector cells

  14. Aged Chinese-origin rhesus macaques infected with SIV develop marked viremia in absence of clinical disease, inflammation or cognitive impairment.

    Science.gov (United States)

    Bissel, Stephanie J; Gurnsey, Kate; Jedema, Hank P; Smith, Nicholas F; Wang, Guoji; Bradberry, Charles W; Wiley, Clayton A

    2018-02-01

    Damage to the central nervous system during HIV infection can lead to variable neurobehavioral dysfunction termed HIV-associated neurocognitive disorders (HAND). There is no clear consensus regarding the neuropathological or cellular basis of HAND. We sought to study the potential contribution of aging to the pathogenesis of HAND. Aged (range = 14.7-24.8 year) rhesus macaques of Chinese origin (RM-Ch) (n = 23) were trained to perform cognitive tasks. Macaques were then divided into four groups to assess the impact of SIVmac251 infection (n = 12) and combined antiretroviral therapy (CART) (5 infected; 5 mock-infected) on the execution of these tasks. Aged SIV-infected RM-Ch demonstrated significant plasma viremia and modest CSF viral loads but showed few clinical signs, no elevations of systemic temperature, and no changes in activity levels, platelet counts or weight. Concentrations of biomarkers of acute and chronic inflammation such as soluble CD14, CXCL10, IL-6 and TNF-α are known to be elevated following SIV infection of young adult macaques of several species, but concentrations of these biomarkers did not shift after SIV infection in aged RM-Ch and remained similar to mock-infected macaques. Neither acute nor chronic SIV infection or CART had a significant impact on accuracy, speed or percent completion in a sensorimotor test. Viremia in the absence of a chronic elevated inflammatory response seen in some aged RM-Ch is reminiscent of SIV infection in natural disease resistant hosts. The absence of cognitive impairment during SIV infection in aged RM-Ch might be in part attributed to diminishment of some facets of the immunological response. Additional study encompassing species and age differences is necessary to substantiate this hypothesis.

  15. Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells.

    Directory of Open Access Journals (Sweden)

    Manjunatha M Venkataswamy

    Full Text Available Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT cells to enhance priming of CD8+ T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag. We found that the incorporation of the synthetic NKT activating glycolipid α-galactosylceramide (α-GC into rBCG-SIV gag significantly enhanced CD8+ T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of α-GC to enhance CD8+ T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an α-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG.vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8+ T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors.

  16. Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells.

    Science.gov (United States)

    Venkataswamy, Manjunatha M; Ng, Tony W; Kharkwal, Shalu S; Carreño, Leandro J; Johnson, Alison J; Kunnath-Velayudhan, Shajo; Liu, Zheng; Bittman, Robert; Jervis, Peter J; Cox, Liam R; Besra, Gurdyal S; Wen, Xiangshu; Yuan, Weiming; Tsuji, Moriya; Li, Xiangming; Ho, David D; Chan, John; Lee, Sunhee; Frothingham, Richard; Haynes, Barton F; Panas, Michael W; Gillard, Geoffrey O; Sixsmith, Jaimie D; Korioth-Schmitz, Birgit; Schmitz, Joern E; Larsen, Michelle H; Jacobs, William R; Porcelli, Steven A

    2014-01-01

    Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG) has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT) cells to enhance priming of CD8+ T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag). We found that the incorporation of the synthetic NKT activating glycolipid α-galactosylceramide (α-GC) into rBCG-SIV gag significantly enhanced CD8+ T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of α-GC to enhance CD8+ T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an α-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG.vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8+ T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors.

  17. ROTAVIRUS VACCINES

    OpenAIRE

    Kang, G

    2006-01-01

    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 intuss...

  18. The future of human DNA vaccines

    Science.gov (United States)

    Li, Lei; Saade, Fadi; Petrovsky, Nikolai

    2012-01-01

    DNA vaccines have evolved greatly over the last 20 years since their invention, but have yet to become a competitive alternative to conventional protein or carbohydrate based human vaccines. Whilst safety concerns were an initial barrier, the Achilles heel of DNA vaccines remains their poor immunogenicity when compared to protein vaccines. A wide variety of strategies have been developed to optimize DNA vaccine immunogenicity, including codon optimization, genetic adjuvants, electroporation and sophisticated prime-boost regimens, with each of these methods having its advantages and limitations. Whilst each of these methods has contributed to incremental improvements in DNA vaccine efficacy, more is still needed if human DNA vaccines are to succeed commercially. This review foresees a final breakthrough in human DNA vaccines will come from application of the latest cutting-edge technologies, including “epigenetics” and “omics” approaches, alongside traditional techniques to improve immunogenicity such as adjuvants and electroporation, thereby overcoming the current limitations of DNA vaccines in humans PMID:22981627

  19. Safety profile of the 9-valent HPV vaccine

    DEFF Research Database (Denmark)

    Moreira, Edson D; Block, Stan L; Ferris, Daron G

    2016-01-01

    OBJECTIVES: The overall safety profile of the 9-valent human papillomavirus (9vHPV) vaccine was evaluated across 7 Phase III studies, conducted in males and females (nonpregnant at entry), 9 to 26 years of age. METHODS: Vaccination was administered as a 3-dose regimen at day 1, and months 2 and 6....... More than 15 000 subjects received ≥1 dose of 9vHPV vaccine. In 2 of the studies, >7000 control subjects received ≥1 dose of quadrivalent HPV (qHPV) vaccine. Serious and nonserious adverse events (AEs) and new medical conditions were recorded throughout the study. Subjects testing positive...... for pregnancy at day 1 were not vaccinated; those who became pregnant after day 1 were discontinued from further vaccination until resolution of the pregnancy. Pregnancies detected after study start (n = 2950) were followed to outcome. RESULTS: The most common AEs (≥5%) experienced by 9vHPV vaccine recipients...

  20. Contraceptive Vaccines

    Directory of Open Access Journals (Sweden)

    M.V. Supotnitsky

    2014-02-01

    Full Text Available Researches to develop vaccines with contraceptive effect are being carried out since the 1920s. Since 1972, the contraceptive vaccines are one of the priority programs of the World Health Organization (WHO Special Programme of Research, Development and Research Training in Human Reproduction. Rockefeller Foundation participates in implementing the program. Openly declared objective of creating such vaccines — the regulation of the population in the Third World countries. There are currently three main directions of contraceptive vaccine design: 1 vaccines targeted at blocking the production of gametes; 2 impairing their function; 3 violating the fertilization process. Contraceptive vaccines for more than 10 years are widely used to reduce fertility and castration of wild and domestic animals. In the commercial realization there are veterinary vaccines Equity®, Improvac®, GonaCon®, Repro-BLOC (based on gonadotropin-releasing hormone; SpayVac™ and IVT-PZP® (based on zona pellucida antigens. Clinical studies have shown effective contraceptive action (in women of vaccines, in which human chorionic gonadotropin is used as an antigen. At the same time, there are found the side effects of such vaccines: for vaccines containing gonadotropin-releasing hormone and luteinizing hormone as antigenic components — castration, impotence; for vaccines containing follicle stimulating hormone — oligospermia; zona pellucida antigens — irreversible oophoritis. This paper discusses approaches to detection of sterilizing components in vaccines intended for mass prevention of infectious diseases, not reported by manufacturers, and the consequences of their use. Hidden use of contraceptive vaccines, which already took place, can be detected: 1 by the presence of antibodies to their antigenic components (in unvaccinated by contraceptive vaccines people such antibodies do not exist, except infertility cases; 2 by change in the hormonal levels of the

  1. FLU VACCINATION

    CERN Document Server

    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

  2. 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

  3. 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

  4. SIV-infected Chinese-origin rhesus macaques express specific MHC class I alleles in either elite controllers or normal progressors

    OpenAIRE

    Wambua, Daniel; Henderson, Ryan; Solomon, Christopher; Hunter, Meredith; Marx, Preston; Sette, Alessandro; Mothé, Bianca R.

    2011-01-01

    We characterized twelve SIV-infected Chinese-origin rhesus macaques for their entire MHC class I allele composition. Several MHC class I alleles were present in animals with varying outcomes of infections, either elite control or normal progression to AIDS disease. These MHC class I alleles may prove interesting targets for additional characterization.

  5. SIV-infected Chinese-origin rhesus macaques express specific MHC class I alleles in either elite controllers or normal progressors

    Science.gov (United States)

    Wambua, Daniel; Henderson, Ryan; Solomon, Christopher; Hunter, Meredith; Marx, Preston; Sette, Alessandro; Mothé, Bianca R.

    2011-01-01

    We characterized twelve SIV-infected Chinese-origin rhesus macaques for their entire MHC class I allele composition. Several MHC class I alleles were present in animals with varying outcomes of infections, either elite control or normal progression to AIDS disease. These MHC class I alleles may prove interesting targets for additional characterization. PMID:21781132

  6. Distinct phenotype, longitudinal changes of numbers and cell-associated virus in blood dendritic cells in SIV-infected CD8-lymphocyte depleted macaques.

    Directory of Open Access Journals (Sweden)

    Caroline Soulas

    Full Text Available Loss of circulating CD123+ plasmacytoid dendritic cells (pDCs during HIV infection is well established. However, changes of myeloid DCs (mDCs are ambiguous since they are studied as a homogeneous CD11c+ population despite phenotypic and functional heterogeneity. Heterogeneity of CD11c+ mDCs in primates is poorly described in HIV and SIV infection. Using multiparametric flow cytometry, we monitored longitudinally cell number and cell-associated virus of CD123+ pDCs and non-overlapping subsets of CD1c+ and CD16+ mDCs in SIV-infected CD8-depleted rhesus macaques. The numbers of all three DC subsets were significantly decreased by 8 days post-infection. Whereas CD123+ pDCs were persistently depleted, numbers of CD1c+ and CD16+ mDCs rebounded. Numbers of CD1c+ mDCs significantly increased by 3 weeks post-infection while numbers of CD16+ mDCs remained closer to pre-infection levels. We found similar changes in the numbers of all three DC subsets in CD8 depleted animals as we found in animals that were SIV infected animals that were not CD8 lymphocyte depleted. CD16+ mDCs and CD123+ pDCs but not CD1c+ mDCs were significantly decreased terminally with AIDS. All DC subsets harbored SIV RNA as early as 8 days and then throughout infection. However, SIV DNA was only detected in CD123+ pDCs and only at 40 days post-infection consistent with SIV RNA, at least in mDCs, being surface-bound. Altogether our data demonstrate that SIV infection differently affects CD1c+ and CD16+ mDCs where CD16+ but not CD1c+ mDCs are depleted and might be differentially regulated in terminal AIDS. Finally, our data underline the importance of studying CD1c+ and CD16+ mDCs as discrete populations, and not as total CD11c+ mDCs.

  7. Immunogenicity and Safety of an Inactivated Rift Valley Fever Vaccine in a 19-Year Study

    Science.gov (United States)

    2011-02-26

    quently emerged in the Mideast [4,5]. Introduction of RVF virus to areas of the world where the Aedes mosquito vector resides could have a significant...against lethal Rift Valley fever (RVFV) infection in transgenic IFNAR(−/−) mice induced by different DNA vaccination regimens. Vaccine 2010;28:2937–44

  8. Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburg virus in nonhuman primates

    NARCIS (Netherlands)

    Geisbert, Thomas W.; Bailey, Michael; Geisbert, Joan B.; Asiedu, Clement; Roederer, Mario; Grazia-Pau, Maria; Custers, Jerome; Jahrling, Peter; Goudsmit, Jaap; Koup, Richard; Sullivan, Nancy J.

    2010-01-01

    The immunogenicity and durability of genetic vaccines are influenced by the composition of gene inserts and choice of delivery vector. DNA vectors are a promising vaccine approach showing efficacy when combined in prime-boost regimens with recombinant protein or viral vectors, but they have shown

  9. Flu Vaccination

    CERN Document Server

    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

  10. FLU VACCINATION

    CERN Document Server

    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

  11. 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

  12. 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

  13. High expression levels of BLyS/BAFF by blood dendritic cells and granulocytes are associated with B-cell dysregulation in SIV-infected rhesus macaques.

    Science.gov (United States)

    Poudrier, Johanne; Soulas, Caroline; Chagnon-Choquet, Josiane; Burdo, Tricia; Autissier, Patrick; Oskar, Kathryn; Williams, Kenneth C; Roger, Michel

    2015-01-01

    Dendritic cells (DCs) modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF). In recent longitudinal studies involving HIV-1-infected individuals with different rates of disease progression, we have shown that DCs were altered in number and phenotype in the context of HIV-1 disease progression and B-cell dysregulations were associated with increased BLyS/BAFF expression in plasma and by blood myeloid DCs (mDCs) in rapid and classic progressors but not in HIV-1-elite controllers (EC). Suggesting that the extent to which HIV-1 disease progression is controlled may be linked to BLyS/BAFF expression status and the capacity to orchestrate B-cell responses. Herein, longitudinal analyses of simian immunodeficiency virus (SIV)-infected rhesus macaques also revealed increased expression of BLyS/BAFF by blood mDCs as soon as day 8 and throughout infection. Strikingly, granulocytes presented the highest BLyS/BAFF expression profile in the blood of SIV-infected macaques. BLyS/BAFF levels were also increased in plasma and correlated with viral loads. Consequently, these SIV-infected animals had plasma hyperglobulinemia and reduced blood B-cell numbers with altered population frequencies. These data underscore that BLyS/BAFF is associated with immune dysregulation in SIV-infected rhesus macaques and suggest that BLyS/BAFF is a key regulator of immune activation that is highly conserved among primates. These findings emphasize the potential importance of this SIV-infected primate model to test whether blocking excess BLyS/BAFF has an effect on the overall inflammatory burden and immune restoration.

  14. High expression levels of BLyS/BAFF by blood dendritic cells and granulocytes are associated with B-cell dysregulation in SIV-infected rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Johanne Poudrier

    Full Text Available Dendritic cells (DCs modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF. In recent longitudinal studies involving HIV-1-infected individuals with different rates of disease progression, we have shown that DCs were altered in number and phenotype in the context of HIV-1 disease progression and B-cell dysregulations were associated with increased BLyS/BAFF expression in plasma and by blood myeloid DCs (mDCs in rapid and classic progressors but not in HIV-1-elite controllers (EC. Suggesting that the extent to which HIV-1 disease progression is controlled may be linked to BLyS/BAFF expression status and the capacity to orchestrate B-cell responses. Herein, longitudinal analyses of simian immunodeficiency virus (SIV-infected rhesus macaques also revealed increased expression of BLyS/BAFF by blood mDCs as soon as day 8 and throughout infection. Strikingly, granulocytes presented the highest BLyS/BAFF expression profile in the blood of SIV-infected macaques. BLyS/BAFF levels were also increased in plasma and correlated with viral loads. Consequently, these SIV-infected animals had plasma hyperglobulinemia and reduced blood B-cell numbers with altered population frequencies. These data underscore that BLyS/BAFF is associated with immune dysregulation in SIV-infected rhesus macaques and suggest that BLyS/BAFF is a key regulator of immune activation that is highly conserved among primates. These findings emphasize the potential importance of this SIV-infected primate model to test whether blocking excess BLyS/BAFF has an effect on the overall inflammatory burden and immune restoration.

  15. Leptospirosis vaccines

    OpenAIRE

    Jin Li; Wang Zhijun; Węgrzyn Alicja

    2007-01-01

    Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the...

  16. Combination Vaccines

    OpenAIRE

    Skibinski, David AG; Baudner, Barbara C; Singh, Manmohan; O’Hagan, Derek T

    2011-01-01

    The combination of diphtheria, tetanus, and pertussis vaccines into a single product has been central to the protection of the pediatric population over the past 50 years. The addition of inactivated polio, Haemophilus influenzae, and hepatitis B vaccines into the combination has facilitated the introduction of these vaccines into recommended immunization schedules by reducing the number of injections required and has therefore increased immunization compliance. However, the development of th...

  17. Tumor vaccines:

    OpenAIRE

    Frank, Mojca; Ihan, Alojz

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regirrcents. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tccmor aaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which imrrtune tol...

  18. Immunogenicity of HPV prophylactic vaccines: Serology assays and their use in HPV vaccine evaluation and development.

    Science.gov (United States)

    Pinto, Ligia A; Dillner, Joakim; Beddows, Simon; Unger, Elizabeth R

    2018-01-17

    When administered as standard three-dose schedules, the licensed HPV prophylactic vaccines have demonstrated extraordinary immunogenicity and efficacy. We summarize the immunogenicity of these licensed vaccines and the most commonly used serology assays, with a focus on key considerations for one-dose vaccine schedules. Although immune correlates of protection against infection are not entirely clear, both preclinical and clinical evidence point to neutralizing antibodies as the principal mechanism of protection. Thus, immunogenicity assessments in vaccine trials have focused on measurements of antibody responses to the vaccine. Non-inferiority of antibody responses after two doses of HPV vaccines separated by 6 months has been demonstrated and this evidence supported the recent WHO recommendations for two-dose vaccination schedules in both boys and girls 9-14 years of age. There is also some evidence suggesting that one dose of HPV vaccines may provide protection similar to the currently recommended two-dose regimens but robust data on efficacy and immunogenicity of one-dose vaccine schedules are lacking. In addition, immunogenicity has been assessed and reported using different methods, precluding direct comparison of results between different studies and vaccines. New head-to-head vaccine trials evaluating one-dose immunogenicity and efficacy have been initiated and an increase in the number of trials relying on immunobridging is anticipated. Therefore, standardized measurement and reporting of immunogenicity for the up to nine HPV types targeted by the current vaccines is now critical. Building on previous HPV serology assay standardization and harmonization efforts initiated by the WHO HPV LabNet in 2006, new secondary standards, critical reference reagents and testing guidelines will be generated as part of a new partnership to facilitate harmonization of the immunogenicity testing in new HPV vaccine trials. Copyright © 2018 Elsevier Ltd. All rights

  19. Gemcitabine and Vinorelbine (GemVin) Regimen.

    Science.gov (United States)

    Shang, Elizabeth Y; Solimando, Dominic A; Waddell, J Aubrey

    2014-06-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

  20. Prophylactic antibiotic regimens in tumour surgery (PARITY)

    DEFF Research Database (Denmark)

    Petersen, Michael Mørk; Hettwer, Werner H; Grum-Schwensen, Tomas

    2015-01-01

    (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73......OBJECTIVE: Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five...... to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. RESULTS: We screened 96 patients and enrolled 60 participants...

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

    Directory of Open Access Journals (Sweden)

    Abderaouf Damouche

    2015-09-01

    Full Text Available Two of the crucial aspects of human immunodeficiency virus (HIV infection are (i viral persistence in reservoirs (precluding viral eradication and (ii chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART-controlled HIV-infected patients. The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF; the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV. The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART. Data on the impact of HIV on the SVF (especially in individuals not receiving ART are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low

  3. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection

    Science.gov (United States)

    Damouche, Abderaouf; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine

    2015-01-01

    Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic

  4. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

    Science.gov (United States)

    Damouche, Abderaouf; Lazure, Thierry; Avettand-Fènoël, Véronique; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine

    2015-09-01

    Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic

  5. Successful Treatment of Disseminated Bacillus Calmette-Guérin Disease in an HIV-Infected Child with a Linezolid-Containing Regimen

    Directory of Open Access Journals (Sweden)

    Srđan Roglić

    2016-01-01

    Full Text Available Upon HIV infection diagnosis, an 8-month-old boy was transferred for evaluation of worsening respiratory distress requiring mechanical ventilation. Pneumocystis jirovecii pneumonia (PCP was diagnosed; the boy also had a nonhealing ulcer at the site of vaccination with Statens Serum Institut (Danish strain Bacillus Calmette-Guérin (BCG vaccine and associated axillary lymphadenopathy. PCP treatment resulted in weaning from mechanical ventilation. Antimycobacterial treatment was immediately attempted but was discontinued because of hepatotoxicity. Over several months, he developed splenic lesions and then disseminated skin and cystic bone lesions. M. bovis was repeatedly cultured from both skin and bone lesions despite various multidrug antimycobacterial regimens which included linezolid. Eventually, treatment with a regimen of rifabutin, isoniazid, ethambutol, and linezolid led to definitive cure. Clinicians should consider a linezolid-containing regimen for treatment of severe disseminated BCG infection, especially if other drug regimens have failed. Although drug toxicity is a particular concern for young children, this patient received linezolid for 13 months without serious toxicity. This case also highlights the need for universal screening among pregnant women to prevent vertical transmission of HIV. Finally, routine immunization with BCG vaccine at birth should be questioned in countries with low and declining burden of tuberculosis.

  6. Elicitation of Both Anti HIV-1 Env Humoral and Cellular Immunities by Replicating Vaccinia Prime Sendai Virus Boost Regimen and Boosting by CD40Lm

    Science.gov (United States)

    Zhang, Xianfeng; Sobue, Tomoyoshi; Isshiki, Mao; Makino, Shun-ichi; Inoue, Makoto; Kato, Kazunori; Shioda, Tatsuo; Ohashi, Takashi; Sato, Hirotaka; Komano, Jun; Hanabusa, Hideji; Shida, Hisatoshi

    2012-01-01

    For protection from HIV-1 infection, a vaccine should elicit both humoral and cell-mediated immune responses. A novel vaccine regimen and adjuvant that induce high levels of HIV-1 Env-specific T cell and antibody (Ab) responses was developed in this study. The prime-boost regimen that used combinations of replication-competent vaccinia LC16m8Δ (m8Δ) and Sendai virus (SeV) vectors expressing HIV-1 Env efficiently produced both Env-specific CD8+ T cells and anti-Env antibodies, including neutralizing antibodies (nAbs). These results sharply contrast with vaccine regimens that prime with an Env expressing plasmid and boost with the m8Δ or SeV vector that mainly elicited cellular immunities. Moreover, co-priming with combinations of m8Δs expressing Env or a membrane-bound human CD40 ligand mutant (CD40Lm) enhanced Env-specific CD8+ T cell production, but not anti-Env antibody production. In contrast, priming with an m8Δ that coexpresses CD40Lm and Env elicited more anti-Env Abs with higher avidity, but did not promote T cell responses. These results suggest that the m8Δ prime/SeV boost regimen in conjunction with CD40Lm expression could be used as an immunization platform for driving both potent cellular and humoral immunities against pathogens such as HIV-1. PMID:23236521

  7. 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

  8. HPV vaccine

    African Journals Online (AJOL)

    campaign of human papillomavirus (HPV) vaccination of grade 4 girls in South African (SA) public schools, ... This use is of concern in view of the billions of US dollars GSK had to pay for bribery in the USA, and is ... argument used to entice parents to have their daughters vaccinated is to prevent 3 000 women from dying of ...

  9. Flublok Seasonal Influenza (Flu) Vaccination

    Science.gov (United States)

    ... Vaccine Safety and Pregnant Women Febrile Seizures Following Vaccination Flu Vaccine and People with Egg Allergies Guillain- ... Flu Vaccines Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination Fluzone High-Dose Seasonal Influenza Vaccine Cell-Based ...

  10. Combination vaccines

    Directory of Open Access Journals (Sweden)

    David AG Skibinski

    2011-01-01

    Full Text Available The combination of diphtheria, tetanus, and pertussis vaccines into a single product has been central to the protection of the pediatric population over the past 50 years. The addition of inactivated polio, Haemophilus influenzae, and hepatitis B vaccines into the combination has facilitated the introduction of these vaccines into recommended immunization schedules by reducing the number of injections required and has therefore increased immunization compliance. However, the development of these combinations encountered numerous challenges, including the reduced response to Haemophilus influenzae vaccine when given in combination; the need to consolidate the differences in the immunization schedule (hepatitis B; and the need to improve the safety profile of the diphtheria, tetanus, and pertussis combination. Here, we review these challenges and also discuss future prospects for combination vaccines.

  11. Re-designing the Mozambique vaccine supply chain to improve access to vaccines.

    Science.gov (United States)

    Lee, Bruce Y; Haidari, Leila A; Prosser, Wendy; Connor, Diana L; Bechtel, Ruth; Dipuve, Amelia; Kassim, Hidayat; Khanlawia, Balbina; Brown, Shawn T

    2016-09-22

    Populations and routine childhood vaccine regimens have changed substantially since supply chains were designed in the 1980s, and introducing new vaccines during the "Decade of Vaccine" may exacerbate existing bottlenecks, further inhibiting the flow of all vaccines. Working with the Mozambique Ministry of Health, our team implemented a new process that integrated HERMES computational simulation modeling and on-the-ground implementers to evaluate and improve the Mozambique vaccine supply chain using a system-re-design that integrated new supply chain structures, information technology, equipment, personnel, and policies. The alternative system design raised vaccine availability (from 66% to 93% in Gaza; from 76% to 84% in Cabo Delgado) and reduced the logistics cost per dose administered (from $0.53 to $0.32 in Gaza; from $0.38 to $0.24 in Cabo Delgado) as compared to the multi-tiered system under the current EPI. The alternative system also produced higher availability at lower costs after new vaccine introductions. Since reviewing scenarios modeling deliveries every two months in the north of Gaza, the provincial directorate has decided to pilot this approach diverging from decades of policies dictating monthly deliveries. Re-design improved not only supply chain efficacy but also efficiency, important since resources to deliver vaccines are limited. The Mozambique experience and process can serve as a model for other countries during the Decade of Vaccines. For the Decade of Vaccines, getting vaccines at affordable prices to the market is not enough. Vaccines must reach the population to be successful. Copyright © 2016. Published by Elsevier Ltd.

  12. A Randomized Controlled Trial to Evaluate a Potential Hepatitis B Booster Vaccination Strategy Using Combined Hepatitis A and B Vaccine.

    Science.gov (United States)

    Li, Fangjun; Hu, Yuansheng; Zhou, Youming; Chen, Lixin; Xia, Wei; Song, Yufei; Tan, Zhengliang; Gao, Lidong; Yang, Zhong; Zeng, Gang; Han, Xing; Li, Junhua; Li, Jing

    2017-05-01

    Booster doses could play a major role in no responders or low responders to primary hepatitis B (HB) vaccine. Planed time point for hepatitis A vaccination in China provides a good opportunity to carry out HB booster dose by using combined hepatitis A and B vaccine. A randomized, double-blinded clinical trial was conducted to compare the immunogenicity and safety of toddlers 18-24 months of age receiving 3 different vaccination regimens: 2 doses of inactivated hepatitis A vaccine (group 1), 1 dose of inactivated hepatitis A vaccine plus 1 dose of combined hepatitis A and B vaccine (group 2) or 2 doses of combined hepatitis A and B vaccine (group 3). All 3 groups showed 100% seroprotection for antihepatitis A virus antibody after vaccination. Seroprotection rate for anti-HB antibody before vaccination ranged from 79.5% to 92.9% in the 3 groups. After second inoculation, anti-HBs seroprotection increased from 92.9% to 100% in group 2 with postvaccination geometric mean concentration (GMC) of 2258.3 mIU/mL and from 79.5% to 98.9% in group 3 with postvaccination GMC of 2055.3 mIU/mL. The adverse events were not statistically different among groups (P = 0.345). Combined hepatitis A and B vaccine could stimulate high level of both antihepatitis A virus and anti-HBs antibodies and not increase adverse events, providing a new choice for HB booster.

  13. Full-length genome sequence of a simian immunodeficiency virus (SIV) infecting a captive agile mangabey (Cercocebus agilis) is closely related to SIVrcm infecting wild red-capped mangabeys (Cercocebus torquatus) in Cameroon.

    Science.gov (United States)

    Ahuka-Mundeke, Steve; Liegeois, Florian; Ayouba, Ahidjo; Foupouapouognini, Yacouba; Nerrienet, Eric; Delaporte, Eric; Peeters, Martine

    2010-12-01

    Simian immunodeficiency viruses (SIVs) are lentiviruses that infect an extensive number of wild African primate species. Here we describe for the first time SIV infection in a captive agile mangabey (Cercocebus agilis) from Cameroon. Phylogenetic analysis of the full-length genome sequence of SIVagi-00CM312 showed that this novel virus fell into the SIVrcm lineage and was most closely related to a newly characterized SIVrcm strain (SIVrcm-02CM8081) from a wild-caught red-capped mangabey (Cercocebus torquatus) from Cameroon. In contrast to red-capped mangabeys, no 24 bp deletion in CCR5 has been observed in the agile mangabey. Further studies on wild agile mangabeys are needed to determine whether agile and red-capped mangabeys are naturally infected with the same SIV lineage, or whether this agile mangabey became infected with an SIVrcm strain in captivity. However, our study shows that agile mangabeys are susceptible to SIV infection.

  14. "Eesti taluarhitektuur. Püsiv ja muutuv : Eesti Vabaõhumuuseumi näitus = Estonian farm architecture. Enduring and changing : an Estonian Open Air Museum exhibition / Heiki Pärdi

    Index Scriptorium Estoniae

    Pärdi, Heiki, 1951-

    2015-01-01

    Eesti Vabaõhumuuseumi näitus "Eesti taluarhitektuur. Püsiv ja muutuv". Näituse autor Heiki Pärdi, kuraator Elo Lutsepp, kujundaja Jan Skolimowski (KAMP Arhitektid). 2014. aasta Kultuurkapitali Arhitektuuripreemia kandidaat

  15. Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses.

    Science.gov (United States)

    Tang, Xian; Guo, Jia; Cheng, Lin; Sun, Caijun; Liu, Li; Zuo, Teng; Wang, Hui; Chen, Ling; Zhang, Linqi; Chen, Zhiwei

    2017-05-02

    An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified. Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells. Here we report that both DNA- and vaccinia-based vaccines encoding SIV mac239 gp160 readily elicited high levels of CD4i Abs in experimental animals. We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain. Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively. Importantly, immune sera elicited by the N277A-mutated gp160 exhibited elevated antibody-dependent cellular cytotoxicity (ADCC) activity. ADCC activity correlated positively with the anti-V2 Ab titer yet, inversely with CD4i Ab titer. Thus, we identified a determinant of the CD4i domain that might affect vaccine-elicited anti-V2 Ab and ADCC responses to SIV mac239 . Our findings may have implications for design of immunogens to direct B cell recognition in the development of an Ab-based HIV vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Randomized trial to compare the safety and immunogenicity of CSL Limited's 2009 trivalent inactivated influenza vaccine to an established vaccine in United States children.

    Science.gov (United States)

    Brady, Rebecca C; Hu, Wilson; Houchin, Vonda G; Eder, Frank S; Jackson, Kenneth C; Hartel, Gunter F; Sawlwin, Daphne C; Albano, Frank R; Greenberg, Michael

    2014-12-12

    A trivalent inactivated influenza vaccine (CSL's TIV, CSL Limited) was licensed under USA accelerated approval regulations for use in persons≥18 years. We performed a randomized, observer-blind study to assess the safety and immunogenicity of CSL's TIV versus an established US-licensed vaccine in a population≥6 months to vaccination history determined the dosing regimen (one or two vaccinations). Subjects received CSL's TIV (n=739) or the established vaccine (n=735) in the autumn of 2009. Serum hemagglutination-inhibition titers were determined pre-vaccination and 30 days after the last vaccination. No febrile seizures or other vaccine-related SAEs were reported. After the first vaccination for Cohorts A and B, respectively, the relative risks of fever were 2.73 and 2.32 times higher for CSL's TIV compared to the established vaccine. Irritability and loss of appetite (for Cohort A) and malaise (for Cohort B) were also significantly higher for CSL's TIV compared to the established vaccine. Post-vaccination geometric mean titers (GMTs) for CSL's TIV versus the established vaccine were 385.49 vs. 382.45 for H1N1; 669.13 vs. 705.61 for H3N2; and 100.65 vs. 93.72 for B. CSL's TIV demonstrated immunological non-inferiority to the established vaccine in all cohorts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Intradermal vaccination against hepatitis B in a group of medical ...

    African Journals Online (AJOL)

    A prospective study of a low-dose (one-tenth) intradermal regimen using recombinant hepatitis B vaccine was undertaken during two consecutive years in 4th-year medical students. Eighty one per cent of the vaccinees (123/152) seroconverted with anti-HBs levels of > 10 lU/l. The lower titre of hepatitis B surface antibodies ...

  18. Rapid outer-surface protein C DNA tattoo vaccination protects against Borrelia afzelii infection.

    Science.gov (United States)

    Wagemakers, A; Mason, L M K; Oei, A; de Wever, B; van der Poll, T; Bins, A D; Hovius, J W R

    2014-12-01

    Borrelia afzelii is the predominant Borrelia species causing Lyme borreliosis in Europe. Currently there is no human vaccine against Lyme borreliosis, and most research focuses on recombinant protein vaccines against Borrelia burgdorferi sensu stricto. DNA tattooing is a novel vaccination method that can be applied in a rapid vaccination schedule. We vaccinated C3H/HeN mice with B. afzelii strain PKo OspC (outer-surface protein C) using a codon-optimized DNA vaccine tattoo and compared this with recombinant protein vaccination in a 0-2-4 week vaccination schedule. We also assessed protection by DNA tattoo in a 0-3-6 day schedule. DNA tattoo and recombinant OspC vaccination induced comparable total IgG responses, with a lower IgG1/IgG2a ratio after DNA tattoo. Two weeks after syringe-challenge with 5 × 10(5) B. afzelii spirochetes most vaccinated mice had negative B. afzelii tissue DNA loads and all were culture negative. Furthermore, DNA tattoo vaccination in a 0-3-6 day regimen also resulted in negative Borrelia loads and cultures after challenge. To conclude, DNA vaccination by tattoo was fully protective against B. afzelii challenge in mice in a rapid vaccination protocol, and induces a favorable humoral immunity compared to recombinant protein vaccination. Rapid DNA tattoo is a promising vaccination strategy against spirochetes.

  19. Oral Rabies Vaccine Design for Expression in Plants.

    Science.gov (United States)

    Singh, Ankit; Saxena, Gauri; Verma, Praveen C

    2016-01-01

    Vaccination is the sensitization process of the immune system against any pathogen. Generally, recombinant subunit vaccines are considered safer than attenuated vaccines. As whole pathogenic organisms are used in the immunization process, the attenuated vaccines are considered more risky than subunit vaccines. Rabies is the oldest known zoonosis which spreads through a neurotropic Lyssavirus primarily mediated through infected canine bites. Rabies causes worldwide loss of more than 60,000 human lives every year. Animal vaccination is equally important to check the transmission of rabies into humans. Rabies oral vaccination can be a good alternative where multiple booster and priming regimens are required while the painful vaccination process can continue for long durations. Introduction of oral vaccines was made to ease the discomfort associated with the mode of introduction of conventional vaccines into the body. Although the rabies oral vaccine can substantially reduce the cost of vaccination in the developing countries, mass immunization programs need larger quantities of vaccines which should be delivered at nominal cost. Expression of recombinant antigen proteins in E. coli is often not viable because of lack of post-translational modifications and folding requirements. Though yeast and insect cell line expression systems have post-translational processing and modifications, significantly different immunological response against their post-translational modification pattern limits their deployment as an expression system. As an alternative, plants are emerging as a promising system to express and deliver wide range of functionally active biopharmaceutical product at lower cost for mass immunization programs. As generation of vaccine antigenic proteins in plant systems are cheaper, the strategy will benefit developing countries where this disease causes thousands of deaths every year. In this chapter, we will discuss about our efforts toward development of oral

  20. Tumor vaccines

    International Nuclear Information System (INIS)

    Frank, M.; Ihan, A.

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regiments. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tumor vaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which immune tolerance exists. That is why the population of tumor-specific lymphocytes is represented by a small number of low-affinity T-lymphocytes that induce weak antitumor immune response. Simultaneously, tumors evolve many mechanisms to actively evade immune system, what makes them poorly immunogenic or even tolerogenic. Novel immunotherapeutic strategies are directed toward breaking immune tolerance to tumor antigens, enhancing immunogenicity of tumor vaccines and overcoming mechanisms of tumor escape. There are several approaches, unfortunately, all of them still far away from an ideal tumor vaccine that would reject a tumor. Difficulties in the activation of antitumor immune response by tumor vaccines have led to the development of alternative immunotherapeutic strategies that directly focus on effector mechanisms of immune system (adoptive tumor- specific T-lymphocyte transfer and tumor specific monoclonal antibodies). (author)

  1. 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.

  2. Pox-Protein Public Private Partnership program and upcoming HIV vaccine efficacy trials.

    Science.gov (United States)

    Russell, Nina D; Marovich, Mary A

    2016-11-01

    The purpose of review is to provide an overview of the Pox-Protein Public Private Partnership (P5) and highlight the progress of the P5 program, including an upcoming HIV vaccine efficacy trial in South Africa. The RV144 Thai vaccine efficacy trial was the first to demonstrate that an HIV-1 vaccine can prevent HIV acquisition. The P5 vaccine regimen uses an ALVAC prime and protein boost modeled after the RV144 vaccine and adapted for the subtype C virus predominant in the southern African region. This regimen was recently tested in the HIV Vaccine Trials Network 100 phase 1/2a study in South Africa. Based on prospectively defined immunogenicity thresholds, criteria were met to support the launch of an efficacy study in late 2016. The aim of this phase 2b/3 trial will be to improve upon the results of RV144, with increased and more durable vaccine efficacy, to accelerate the potential licensure of a preventive vaccine in southern Africa. The planned P5 efficacy trial, HIV Vaccine Trials Network 702, is designed to test and prospectively define correlates of protection, if efficacious. A vaccine with modest efficacy, vaccine efficacy at least 50%, could have substantial public health impact and significantly decrease the incidence of new infections in heavily burdened areas of the world.

  3. Inappropriate Tuberculosis Treatment Regimens in Chinese Tuberculosis Hospitals

    NARCIS (Netherlands)

    Xue He, Guang; van den Hof, Susan; van der Werf, Marieke J.; Guo, Hui; Hu, Yuan Lian; Fan, Ji Huan; Zhang, Wei Min; Tostado, Christopher P.; Borgdorff, Martien W.

    2011-01-01

    This investigation of tuberculosis (TB) treatment regimens in 6 TB hospitals in China showed that only 18% of patients with new cases and 9% of patients with retreatment cases were prescribed standard TB treatment regimens. Adherence to treatment guidelines needs to be improved in TB hospitals to

  4. The Sex Res Non Naturales and the Regimen of Health

    DEFF Research Database (Denmark)

    Agerholm, Frank Juul

    The paper discusses the ethical and social soundness of the classical idea of diaita/regimen vis-à-vis the contemporary focus on healthy lifestyle......The paper discusses the ethical and social soundness of the classical idea of diaita/regimen vis-à-vis the contemporary focus on healthy lifestyle...

  5. 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

  6. Impact of short-term HAART initiated during the chronic stage or shortly post-exposure on SIV infection of male genital organs.

    Directory of Open Access Journals (Sweden)

    Marina Moreau

    Full Text Available BACKGROUND: The male genital tract is suspected to constitute a viral sanctuary as persistent HIV shedding is found in the semen of a subset of HIV-infected men receiving effective antiretroviral therapy (HAART. The origin of this persistent shedding is currently unknown. Phylogenetic studies indicated that HIV in semen from untreated men arises from local sources and/or passive diffusion from the blood. We previously demonstrated in human and macaque low levels and localized infection of several semen-producing organs by HIV/SIV. Using a macaque model, this study investigates the impact of short term HAART (2-4 weeks initiated either during the asymptomatic chronic stage or 4 h post-intravenous inoculation of SIVmac251 on the infection of male genital organs. METHODOLOGY/PRINCIPAL FINDINGS: Short term HAART during the chronic stage decreased blood viral load. No major impact of HAART was observed on SIV DNA levels in male genital organs using a sensitive nested PCR assay. Using in situ hybridization, SIV RNA+ cells were detected in all male genital tract organs from untreated and treated animals with undetectable blood viral load following HAART. Infected CD68+ myeloid cells and CD3+ T lymphocytes were detected pre- and post-HAART. In contrast, short term HAART initiated 4 h post-SIV exposure led to a drastic decrease of the male genital tissues infection, although it failed to prevent systemic infection. In both cases, HAART tended to decrease the number of CD3+ T cells in the male organs. CONCLUSIONS: Our results indicate that the established infection of male genital organs is not greatly impacted by short term HAART, whereas the same treatment during pre-acute phase of the infection efficiently impairs viral dissemination to the male genital tract. Further investigations are now needed to determine whether infection of male genital organs is responsible for long term persistent HIV shedding in semen despite HAART.

  7. Comparative analysis of immune activation markers of CD8+ T cells in lymph nodes of different origins in SIV-infected Chinese rhesus macaques

    Directory of Open Access Journals (Sweden)

    Jinbiao Liu

    2016-09-01

    Full Text Available Altered T-cell homeostasis, such as expansion of CD8+ T cells to the secondary lymphatic compartments has been suggested as a mechanism of HIV/SIV-pathogenesis. However, the role of immune activation of CD8+ T cells in the CD4/CD8 turnover and viral replication in these tissues is not completely understood. In the present study, we compared the expression of immune activation markers (CD69 and HLA-DR on CD8+ T cells in the peripheral blood and lymph nodes (LNs of SIV-infected/uninfected Chinese rhesus macaques. SIV-infected macaques had significantly higher percentages of CD8+CD69+ and CD8+HLA-DR+ T cells in all these anatomical compartments than uninfected macaques except for CD8+HLA-DR+ T cells in peripheral blood. LNs that located close to the gastrointestinal (GI tract (colon, mesenteric and iliac LNs of SIV-infected macaques had profoundly lower numbers of CD4+ T cells, but no significantly difference in expression of activation marker (CD8+CD69+ and CD8+HLA-DR+ as compared with the peripheral lymphatic tissues (axillary and inguinal LNs. The CD4/CD8 ratios were negatively correlated with the activation of CD8 T cells in the overall LNs, with further associations with CD8+HLA-DR+ in GI LNs while CD8+CD69+ in peripheral LNs. These observations demonstrate that the increase of CD8+ T cell activation is a contributing factor for the decline of CD4/CD8 ratios in GI system.

  8. 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....

  9. 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 ...

  10. Flu Vaccine Safety Information

    Science.gov (United States)

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

  11. Thimerosal in Flu Vaccine

    Science.gov (United States)

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

  12. Vaccinations during Pregnancy

    Science.gov (United States)

    ... community Home > Pregnancy > Prenatal care > Vaccinations and pregnancy Vaccinations and pregnancy E-mail to a friend Please ... date before you get pregnant. What is a vaccination? A vaccination is a shot that contains a ...

  13. DNA Vaccines Against Anthrax

    National Research Council Canada - National Science Library

    Galloway, Darrell R; Baillie, Les

    2004-01-01

    DNA vaccination is vaccination at its simplest. Due to renewed interest in vaccination against anthrax and other biothreat agents, a genetic immunisation approach offers attractive possibilities for rapid, responsive vaccine development...

  14. Comparison of 2 commercial single-dose Mycoplasma hyopneumoniae vaccines and porcine reproductive and respiratory syndrome virus (PRRSV) vaccines on pigs dually infected with M. hyopneumoniae and PRRSV.

    Science.gov (United States)

    Park, Changhoon; Kang, Ikjae; Seo, Hwi Won; Jeong, Jiwoon; Choi, Kyuhyung; Chae, Chanhee

    2016-04-01

    The objective of this study was to compare the efficacy of 2 different commercial Mycoplasma hyopneumoniae vaccines and porcine reproductive and respiratory syndrome virus (PRRSV) vaccines in regard to growth performance, microbiological and immunological analyses, and pathological observation from wean to finish (175 d of age). Pigs were administered M. hyopneumoniae and PRRSV vaccines at 7 and 21 d of age, respectively, or both at 21 d old and then challenged with both M. hyopneumoniae and PRRSV at 49 d old. Significant (P hyopneumoniae, M. hyopneumoniae-specific interferon-γ secreting cells, and macroscopic and microscopic lung lesions. Induction of interleukin-10 following PRRSV vaccination does not interfere with the immune responses induced by M. hyopneumoniae vaccine. The present study demonstrated that the single-dose vaccination regimen for M. hyopneumoniae and PRRSV vaccine is efficacious for controlling coinfection with M. hyopneumoniae and PRRSV based on clinical, microbiological, immunological, and pathological evaluation.

  15. Different oral corticosteroid regimens for acute asthma.

    Science.gov (United States)

    Normansell, Rebecca; Kew, Kayleigh M; Mansour, George

    2016-05-13

    between a higher dose or longer course and a lower dose or shorter course of prednisolone or dexamethasone, or between prednisolone and dexamethasone.Included studies were generally of reasonable methodological quality. Review authors assessed most outcomes in the review as having low or very low quality, meaning we are not confident in the effect estimates. The predominant reason for downgrading was imprecision, but indirectness and risk of bias also reduced our confidence in some estimates. Evidence is not strong enough to reveal whether shorter or lower-dose regimens are generally less effective than longer or higher-dose regimens, or indeed that the latter are associated with more adverse events. Any changes recommended for current practice should be supported by data from larger, well-designed trials. Varied study design and outcome measures limited the number of meta-analyses that we could perform. Greater emphasis on palatability and on whether some regimens might be easier to adhere to than others could better inform clinical decisions for individual patients.

  16. Reactions of SIV species with organic compounds: formation mechanisms of organo-sulfur derivatives in atmospheric aerosols

    Science.gov (United States)

    Passananti, Monica; Shang, Jing; Dupart, Yoan; Perrier, Sébastien; George, Christian

    2015-04-01

    Secondary organic aerosol (SOA) have an important impact on climate, air quality and human health. However the chemical reactions involved in their formation and growth are not fully understood or well-constrained in climate models. It is well known that inorganic sulfur (mainly in oxidation states (+IV) and (+VI)) plays a key role in aerosol formation, for instance sulfuric acid is known to be a good nucleating gas. In addition, acid-catalyzed heterogeneous reactions of organic compounds has shown to produce new particles, with a clear enhancement in the presence of ozone (Iinuma 2013). Organosulfates have been detected in tropospheric particles and aqueous phases, which suggests they are products of secondary organic aerosol formation process (Tolocka 2012). Originally, the production of organosulfates was explained by the esterification reaction of alcohols, but this reaction in atmosphere is kinetically negligible. Other formation pathways have been suggested such as hydrolysis of peroxides and reaction of organic matter with sulfite and sulfate radical anions (SO3-, SO4-) (Nozière 2010), but it remains unclear if these can completely explain atmospheric organo-sulfur aerosol loading. To better understand the formation of organo-sulfur compounds, we started to investigate the reactivity of SIV species (SO2 and SO32-) with respect to specific functional groups (organic acids and double bonds) on atmospherically relevant carboxylic acids and alkenes. The experiments were carried out in the homogeneous aqueous phase and at the solid-gas interface. A custom built coated-wall flow tube reactor was developed to control relativity humidity, SO2 concentration, temperature and gas flow rate. Homogeneous and heterogeneous reaction kinetics were measured and resulting products were identified using liquid chromatography coupled with an orbitrap mass spectrometer (LC-HR-MS). The experiments were performed with and without the presence of ozone in order to evaluate any

  17. 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

  18. Supplementary Material for: Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

    KAUST Repository

    Najera, Julia

    2016-01-01

    Abstract Background Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. Results We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. Conclusions Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.

  19. Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

    KAUST Repository

    Najera, Julia A.

    2016-04-23

    Background Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. Results We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. Conclusions Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.

  20. HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice.

    Directory of Open Access Journals (Sweden)

    Tsungai Ivai Jongwe

    Full Text Available Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG ΔpanCD auxotroph and modified vaccinia Ankara (MVA vaccines expressing HIV-1C mosaic Gag (GagM were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-GagM vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-GagM and boosting with MVA-GagM elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-GagM only and MVA-GagM only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4+ and CD8+ T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (104 pfu can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C.

  1. 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.

  2. 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.

  3. PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice

    Science.gov (United States)

    Zhou, Jingying; Cheung, Allen K.L.; Tan, Zhiwu; Wang, Haibo; Yu, Wenbo; Du, Yanhua; Kang, Yuanxi; Lu, Xiaofan; Liu, Li; Yuen, Kwok-Yung; Chen, Zhiwei

    2013-01-01

    Viral vector–based vaccines that induce protective CD8+ T cell immunity can prevent or control pathogenic SIV infections, but issues of preexisting immunity and safety have impeded their implementation in HIV-1. Here, we report the development of what we believe to be a novel antigen-targeting DNA vaccine strategy that exploits the binding of programmed death-1 (PD1) to its ligands expressed on dendritic cells (DCs) by fusing soluble PD1 with HIV-1 GAG p24 antigen. As compared with non–DC-targeting vaccines, intramuscular immunization via electroporation (EP) of the fusion DNA in mice elicited consistently high frequencies of GAG-specific, broadly reactive, polyfunctional, long-lived, and cytotoxic CD8+ T cells and robust anti-GAG antibody titers. Vaccination conferred remarkable protection against mucosal challenge with vaccinia GAG viruses. Soluble PD1–based vaccination potentiated CD8+ T cell responses by enhancing antigen binding and uptake in DCs and activation in the draining lymph node. It also increased IL-12–producing DCs and engaged antigen cross-presentation when compared with anti-DEC205 antibody-mediated DC targeting. The high frequency of durable and protective GAG-specific CD8+ T cell immunity induced by soluble PD1–based vaccination suggests that PD1-based DNA vaccines could potentially be used against HIV-1 and other pathogens. PMID:23635778

  4. Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine

    Directory of Open Access Journals (Sweden)

    Faingezicht Idis

    2002-01-01

    protective/seropositive titers for Hib, HB, and tetanus and about 50% for diphtheria and Bordetella pertussis. At 15 months of age, virtually all the toddlers responded with a strong boost response to all the vaccine antigens, whether they received the DTPw-HB/Hib pentavalent vaccine or the DTPw/Hib vaccine as a booster. Both booster regimens were equally well tolerated, indicating that up to five doses of the HB vaccine can be given without impact on safety. Conclusions. Our study confirms that the DTPw-HB/Hib pentavalent vaccine is highly immunogenic as a primary vaccination in children who received an HB vaccine at birth, with the pentavalent combination inducing both persisting immunity and boostable memory. The pentavalent vaccine was safe both for primary and booster vaccinations. Thus, this study in Costa Rican infants supports the routine use of the pentavalent DTPw-HB/Hib vaccine as part of childhood vaccination programs in Latin America and the Caribbean.

  5. Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine

    Directory of Open Access Journals (Sweden)

    Idis Faingezicht

    2002-10-01

    protective/seropositive titers for Hib, HB, and tetanus and about 50% for diphtheria and Bordetella pertussis. At 15 months of age, virtually all the toddlers responded with a strong boost response to all the vaccine antigens, whether they received the DTPw-HB/Hib pentavalent vaccine or the DTPw/Hib vaccine as a booster. Both booster regimens were equally well tolerated, indicating that up to five doses of the HB vaccine can be given without impact on safety. Conclusions. Our study confirms that the DTPw-HB/Hib pentavalent vaccine is highly immunogenic as a primary vaccination in children who received an HB vaccine at birth, with the pentavalent combination inducing both persisting immunity and boostable memory. The pentavalent vaccine was safe both for primary and booster vaccinations. Thus, this study in Costa Rican infants supports the routine use of the pentavalent DTPw-HB/Hib vaccine as part of childhood vaccination programs in Latin America and the Caribbean.

  6. In vivo proton magnetic resonance spectroscopy reveals region specific metabolic responses to SIV infection in the macaque brain

    Directory of Open Access Journals (Sweden)

    Joo Chan-Gyu

    2009-06-01

    Full Text Available Abstract Background In vivo proton magnetic resonance spectroscopy (1H-MRS studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection. Results Changes in the N-acetylaspartate (NAA, choline (Cho, myo-inositol (MI, creatine (Cr and glutamine/glutamate (Glx resonances were quantified both in absolute terms and relative to the creatine resonance. Most abnormalities were observed at the time of peak viremia, 2 weeks post infection (wpi. At that time point, significant decreases in NAA and NAA/Cr, reflecting neuronal injury, were observed only in the frontal cortex. Cr was significantly elevated only in the white matter. Changes in Cho and Cho/Cr were similar across the brain regions, increasing at 2 wpi, and falling below baseline levels at 4 wpi. MI and MI/Cr levels were increased across all brain regions. Conclusion These data best support the hypothesis that different brain regions have variable intrinsic vulnerabilities to neuronal injury caused by the AIDS virus.

  7. Follicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection

    Science.gov (United States)

    Folkvord, Joy M.; Levy, David N.; Rakasz, Eva G.; Connick, Elizabeth

    2016-01-01

    During chronic HIV infection, viral replication is concentrated in secondary lymphoid follicles. Cytotoxic CD8 T cells control HIV replication in extrafollicular regions, but not in the follicle. Here, we show CXCR5hiCD44hiCD8 T cells are a regulatory subset differing from conventional CD8 T cells, and constitute the majority of CD8 T cells in the follicle. This subset, CD8 follicular regulatory T cells (CD8 TFR), expand in chronic SIV infection, exhibit enhanced expression of Tim-3 and IL-10, and express less perforin compared to conventional CD8 T cells. CD8 TFR modestly limit HIV replication in follicular helper T cells (TFH), impair TFH IL-21 production via Tim-3, and inhibit IgG production by B cells during ex vivo HIV infection. CD8 TFR induce TFH apoptosis through HLA-E, but induce less apoptosis than conventional CD8 T cells. These data demonstrate that a unique regulatory CD8 population exists in follicles that impairs GC function in HIV infection. PMID:27716848

  8. DNA prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric simian immunodeficiency virus envelope and Advax delta inulin adjuvant.

    Science.gov (United States)

    Menon, Veena; Ayala, Victor I; Rangaswamy, Sneha P; Kalisz, Irene; Whitney, Stephen; Galmin, Lindsey; Ashraf, Asma; LaBranche, Celia; Montefiori, David; Petrovsky, Nikolai; Kalyanaraman, Vaniambadi S; Pal, Ranajit

    2017-08-01

    The partial success of the RV144 trial underscores the importance of envelope-specific antibody responses for an effective HIV-1 vaccine. Oligomeric HIV-1 envelope proteins delivered with a potent adjuvant are expected to elicit strong antibody responses with broad neutralization specificity. To test this hypothesis, two SIV envelope proteins were formulated with delta inulin-based adjuvant (Advax) and used to immunize nonhuman primates. Oligomeric gp140-gp145 from SIVmac251 and SIVsmE660 was purified to homogeneity. Oligomers showed high-affinity interaction with CD4 and were highly immunogenic in rabbits, inducing Tier 2 SIV-neutralizing antibodies. The immunogenicity of an oligomeric Env DNA prime and protein boost together with Advax was evaluated in Chinese rhesus macaques. DNA administration elicited antibodies to both envelopes, and titres were markedly enhanced following homologous protein boosts via intranasal and intramuscular routes. Strong antibody responses were detected against the V1 and V2 domains of gp120. During peak immune responses, a low to moderate level of neutralizing activity was detected against Tier 1A/1B SIV isolates, with a moderate level noted against a Tier 2 isolate. Increased serum antibody affinity to SIVmac251 gp140 and generation of Env-specific memory B cells were observed in the immunized macaques. Animals were subjected to low-dose intravaginal challenge with SIVmac251 one week after the last protein boost. One out of three immunized animals was protected from infection. Although performed with a small number of macaques, this study demonstrates the utility of oligomeric envelopes formulated with Advax in eliciting broad antibody responses with the potential to provide protection against SIV transmission.

  9. Dose-Related Differences in Effectiveness of Human Papillomavirus Vaccination Against Genital Warts

    DEFF Research Database (Denmark)

    Blomberg, Maria; Dehlendorff, Christian; Sand, Carsten

    2015-01-01

    BACKGROUND: Reducing the number of doses in the human papillomavirus (HPV) vaccination regimen from 3 to 2 could increase coverage rates. In this cohort study, we assessed the risk of genital warts (GWs) according to timing and number of doses of quadrivalent HPV vaccine. METHODS: From population......-based registries, we identified all girls in Denmark born during 1985-1999, for whom information on HPV vaccinations was retrieved. The cohort was followed for GW occurrence during 2006-2012. Incidence rate ratios (IRRs) were calculated by Poisson regression to determine differences in GW rates by number...... of vaccine doses. RESULTS: Of the 550,690 girls in the cohort, 361 734 had been vaccinated. Of these, 25.9% had been vaccinated twice and 58.8% 3 times. The risk of GWs decreased significantly with each additional dose of vaccine. For girls who received 2 doses, extension of the interval between doses...

  10. Co-administration of a meningococcal glycoconjugate ACWY vaccine with travel vaccines: a randomized, open-label, multi-center study.

    Science.gov (United States)

    Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Meyer, Seetha; Forleo-Neto, Eduardo; Gniel, Dieter; Dagnew, Alemnew F; Arora, Ashwani Kumar

    2014-01-01

    Potential interactions between vaccines may compromise the immunogenicity and/or safety of individual vaccines so must be assessed before concomitant administration is recommended. In this study, the immunogenicity and safety of travel vaccines against Japanese encephalitis (JEV) and rabies (PCECV) administered together with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine were evaluated (NCT01466387). Healthy adults aged 18 to ≤60 years were randomized to one of four vaccine regimens: JEV + PCECV + MenACWY-CRM, JEV + PCECV, PCECV or MenACWY-CRM. Immunogenicity at baseline and 28 days post-complete vaccination was assessed by serum bactericidal assay using human complement or neutralization tests. Adverse events (AEs) were collected throughout the study period. JEV + PCECV + MenACWY-CRM was non-inferior to JEV + PCECV. Post-vaccination seroprotective neutralizing titers or concentrations were achieved in 98-99% (JE) and 100% (rabies) of subjects across the vaccine groups. Antibody responses to vaccine meningococcal serogroups were in the same range for MenACWY-CRM and JEV + PCECV + MenACWY-CRM. Rates of reporting of AEs were similar for JEV + PCECV and JEV + PCECV + MenACWY-CRM. MenACWY-CRM was administered with an inactivated adjuvanted JE and a purified chick embryo cell-culture rabies vaccine without compromising immunogenicity or safety of the individual vaccines. These data provide evidence that MenACWY-CRM could be effectively incorporated into travel vaccination programs. NCT01466387. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Genital lesions: An indication for changing ART regimen.

    Science.gov (United States)

    Kumar, S Arun; Kumar, N; Kumarasamy, N

    2011-01-01

    Genital lesions are common in HIV positive patients and aetiology for these are mainly due to HSV, HPV or bacterial. They usually respond to HAART, antiviral or antimicrobials. We are presenting a young patient on HAART with non-healing genital ulcer lesions for sixteen months. He responded well to a change in ART regimen within a period of 15 days. This happened after a change to a more potent ART regimen.

  12. Periodontal Vaccines

    Directory of Open Access Journals (Sweden)

    Daisy Happy

    2013-01-01

    Full Text Available Periodontitis is an infectious disease caused by predominantly gram-negative, anaerobic bacteria like P. gingivalis, A. actinomycetemcomitans T. denticola and T. forsythus etc.. Various immunization approaches both as active and passive immunization, against periodontal pathogens have been explored either using the whole microorganism or their specific virulence factors. Non-human primate and other study models have demonstrated raised production of specific antibody titers against various antigens without any recognizable systemic side-effects. But, the current status of our understanding in the field of vaccines against periodontal disease is incomplete. Ongoing research & collaborative efforts can result in development of functional periodontal vaccine for human use in future.

  13. One-year immunogenicity kinetics and safety of a purified chick embryo cell rabies vaccine and an inactivated Vero cell-derived Japanese encephalitis vaccine administered concomitantly according to a new, 1-week, accelerated primary series.

    Science.gov (United States)

    Cramer, Jakob P; Jelinek, Tomas; Paulke-Korinek, Maria; Reisinger, Emil C; Dieckmann, Sebastian; Alberer, Martin; Bühler, Silja; Bosse, Dietrich; Meyer, Seetha; Fragapane, Elena; Costantini, Marco; Pellegrini, Michele; Lattanzi, Maria; Dovali, Claudia

    2016-03-01

    Conventional rabies pre-exposure prophylaxis (PrEP) and Japanese encephalitis (JE) primary series vaccination regimens each require up to 4 weeks to complete and, thus, may not be feasible for individuals who need these immunizations on short notice. This Phase 3b, randomized, controlled, observer-blind study evaluated the immunogenicity and safety of concomitant administration of a purified chick embryo cell culture rabies vaccine and an inactivated, adsorbed JE vaccine according to an accelerated (1 week) regimen when compared with the conventional regimens (4 weeks). This report describes the kinetics of immune responses up to 1 year after vaccination. A total of 661 healthy adults (18 to ≤65 years) were randomized into the following accelerated or conventional vaccine regimens: Rabies + JE-Conventional, Rabies + JE-Accelerated, Rabies-Conventional and JE-Conventional. Immunogenicity was assessed by virus neutralization tests. Safety and tolerability were also evaluated. Irrespective of rabies vaccination regimen, ≥97% of subjects had adequate levels of rabies virus neutralizing antibody (RVNA) concentrations (≥0.5 IU/ml) up to Day 57, with percentages of subjects with RVNA concentrations ≥0.5 IU/ml at Day 366 ranging between 68% in the Rabies + JE-Accelerated group and 80% of subjects in the Rabies-Conventional group. The Rabies + JE-Accelerated group revealed high JE neutralizing antibody titers at all-time points. At Day 366, the percentage of subjects with antibody titers indicative of seroprotection (PRNT50 titers ≥1:10) remained high across JE vaccine groups (86-94%). The accelerated PrEP rabies and JE vaccination regimens, once licensed, could represent a valid alternative in the short-term to currently recommended conventional regimens. The concomitant administration of these two vaccines does not compromise immune responses to any of the vaccine antigens particularly when aiming for short-term protection. Further evidence

  14. Diversity and Vaccine Controversy

    OpenAIRE

    Frempong, Erica

    2010-01-01

    My area of research dealt with many different aspects of the vaccine movement, the main three were: anti-vaccine sentiments over the Internet, global instances of anti-vaccination efforts, and differences in social class and race in vaccine utilization. I have come to realize that there are two distinct issues arising in the organization that encompasses vaccines. The distinctions are the anti-vaccine movement - the spread of anti-vaccine sentiments over the Internet, and global instances ...

  15. 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 ...

  16. Immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted vaccine coadministered with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine and/or meningococcal conjugate vaccine to healthy girls 11 to 18 years of age: results from a randomized open trial.

    Science.gov (United States)

    Wheeler, Cosette M; Harvey, Bryan M; Pichichero, Michael E; Simon, Michael W; Combs, Stephen P; Blatter, Mark M; Marshall, Gary S; Catteau, Grégory; Dobbelaere, Kurt; Descamps, Dominique; Dubin, Gary; Schuind, Anne

    2011-12-01

    A combined immunization strategy for administration of human papillomavirus (HPV) vaccine with other routine vaccines may lead to better compliance. Reactions and immunologic interference with concomitantly administered vaccines are unpredictable, necessitating clinical evaluation. This was a randomized, open study conducted at 48 centers in the United States (NCT00369824). Healthy girls 11 to 18 years of age were randomized equally to 1 of 6 groups to receive 3 doses of HPV-16/18 AS04-adjuvanted vaccine administered at 0, 1, and 6 or 1, 2, and 7 months, with or without 1 dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) and/or 1 dose of meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MCV4) in different coadministration regimens (1283 girls vaccinated). Coadministered vaccines were injected at separate sites. Antibodies were measured for all vaccine components. Reactogenicity and safety were monitored. The prespecified criteria for noninferiority were met for all primary and secondary immunogenicity end points, demonstrating similar immunogenicity of Tdap and MCV4 when given alone or coadministered with the HPV vaccine. Immunogenicity of the HPV vaccine (in terms of seroconversion rates and geometric mean antibody titers to HPV antigens) was similar, regardless of whether it was given alone or coadministered with Tdap and/or MCV4. No differences were observed in the reactogenicity profile of the HPV vaccine administered alone or coadministered with either Tdap and/or MCV4 in different regimens. Concomitant administration of HPV-16/18 AS04-adjuvanted vaccine with Tdap and/or MCV4 in different regimens did not interfere with the immune response to any of the vaccines and had an acceptable safety profile.

  17. Adjuvant-Specific Genetic and Immune Signatures Associated with Lower SIV Infection Risk in Animal Models | Center for Cancer Research

    Science.gov (United States)

    The Human Immunodeficiency Virus (HIV) vaccine trial, RV144, employed a priming Canarypox-based vector, ALVAC-HIV, along with a boost composed of segments of the HIV envelope protein, gp120, with the adjuvant alum.  Results from the trial suggested the vaccine provided protection and, because of the importance of antibodies to that protection, using an adjuvant that could elicit a stronger immune response might improve efficacy.

  18. Protection of human influenza vaccines against a reassortant swine influenza virus of pandemic H1N1 origin using a pig model.

    Science.gov (United States)

    Arunorat, Jirapat; Charoenvisal, Nataya; Woonwong, Yonlayong; Kedkovid, Roongtham; Jittimanee, Supattra; Sitthicharoenchai, Panchan; Kesdangsakonwut, Sawang; Poolperm, Pariwat; Thanawongnuwech, Roongroje

    2017-10-01

    Since the pandemic H1N1 emergence in 2009 (pdmH1N1), many reassortant pdmH1N1 viruses emerged and found circulating in the pig population worldwide. Currently, commercial human subunit vaccines are used commonly to prevent the influenza symptom based on the WHO recommendation. In case of current reassortant swine influenza viruses transmitting from pigs to humans, the efficacy of current human influenza vaccines is of interest. In this study, influenza A negative pigs were vaccinated with selected commercial human subunit vaccines and challenged with rH3N2. All sera were tested with both HI and SN assays using four representative viruses from the surveillance data in 2012 (enH1N1, pdmH1N1, rH1N2 and rH3N2). The results showed no significant differences in clinical signs and macroscopic and microscopic findings among groups. However, all pig sera from vaccinated groups had protective HI titers to the enH1N1, pdmH1N1 and rH1N2 at 21DPV onward and had protective SN titers only to pdmH1N1and rH1N2 at 21DPV onward. SN test results appeared more specific than those of HI tests. All tested sera had no cross-reactivity against the rH3N2. Both studied human subunit vaccines failed to protect and to stop viral shedding with no evidence of serological reaction against rH3N2. SIV surveillance is essential for monitoring a novel SIV emergence potentially for zoonosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. DNA Vaccines

    Indian Academy of Sciences (India)

    The year 1996 marked the 200th anniversary of the first vaccine developed against smallpox by Edward Jenner. In the now- famous 1796 experiment, Jenner scratched the arm of eight- year-old James Phipps, infecting the boy with cowpox pus taken from a milkmaid carrying the virus. Two months later, he scratched James ...

  20. 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.

  1. Rotavirus Vaccine

    Science.gov (United States)

    ... rotavirus disease was a common and serious health problem for children in the United States. Almost all children in the U.S. had at least one rotavirus infection before their 5th birthday.Every year before the vaccine was available: more ...

  2. Vexing Vaccines

    Science.gov (United States)

    Bowman, Darcia Harris

    2004-01-01

    Schools play a key role in ensuring that children are being immunized against diseases, but conflicting research is making enforcement difficult. This article discusses a growing trend of vaccine avoidance and the endless supply of conflicting information and research about immunization safety. Despite the controversy, many people appear to accept…

  3. Valuing vaccination

    Science.gov (United States)

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

    2014-01-01

    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. PMID:25136129

  4. Heterogeneity of Rabies Vaccination Recommendations across Asia

    Directory of Open Access Journals (Sweden)

    Philippe Buchy

    2017-07-01

    Full Text Available Asian countries bear the greatest burden of the disease, with a majority (59% of rabies-related deaths occurring in Asia. In order to promote best practices, we summarized national human vaccination guidelines across this region, to highlight differences and similarities and to discuss the aspects that would benefit from updates. National management guidelines for rabies were retrieved from various sources to extract information on rabies pre- and post-exposure prophylaxis (PrEP, and PEP, booster vaccination, and route of administration. Rabies guidelines recommendations for wound management and PrEP across Asia are broadly aligned to the World Health Organization (WHO guidelines. For PEP, the 5-dose Essen, and the 4-dose Zagreb are the regimens of choice for intramuscular (IM, and the Thai Red Cross regimen for intradermal (ID, administration. Several national guidelines have yet to endorse ID vaccine administration. Most guidelines recommend rabies immunoglobulin in category III exposures. Booster recommendations are not included in all guidelines, with limited clarity on booster requirement across the spectrum of risk of rabies exposure. In conclusion, national recommendations across Asian countries differ and while some guidelines are closely aligned to the WHO recommendations, resource-saving ID administration and use of rational abbreviated schedules have yet to be endorsed.

  5. Hypofractionation Regimens for Stereotactic Radiotherapy for Large Brain Tumors

    International Nuclear Information System (INIS)

    Yuan Jiankui; Wang, Jian Z.; Lo, Simon; Grecula, John C.; Ammirati, Mario; Montebello, Joseph F.; Zhang Hualin; Gupta, Nilendu; Yuh, William T.C.; Mayr, Nina A.

    2008-01-01

    Purpose: To investigate equivalent regimens for hypofractionated stereotactic radiotherapy (HSRT) for brain tumor treatment and to provide dose-escalation guidance to maximize the tumor control within the normal brain tolerance. Methods and Materials: The linear-quadratic model, including the effect of nonuniform dose distributions, was used to evaluate the HSRT regimens. The α/β ratio was estimated using the Gammaknife stereotactic radiosurgery (GKSRS) and whole-brain radiotherapy experience for large brain tumors. The HSRT regimens were derived using two methods: (1) an equivalent tumor control approach, which matches the whole-brain radiotherapy experience for many fractions and merges it with the GKSRS data for few fractions; and (2) a normal-tissue tolerance approach, which takes advantages of the dose conformity and fractionation of HSRT to approach the maximal dose tolerance of the normal brain. Results: A plausible α/β ratio of 12 Gy for brain tumor and a volume parameter n of 0.23 for normal brain were derived from the GKSRS and whole-brain radiotherapy data. The HSRT prescription regimens for the isoeffect of tumor irradiation were calculated. The normal-brain equivalent uniform dose decreased as the number of fractions increased, because of the advantage of fractionation. The regimens for potential dose escalation of HSRT within the limits of normal-brain tolerance were derived. Conclusions: The designed hypofractionated regimens could be used as a preliminary guide for HSRT dose prescription for large brain tumors to mimic the GKSRS experience and for dose escalation trials. Clinical studies are necessary to further tune the model parameters and validate these regimens

  6. DNA vaccines against leptospirosis: A literature review.

    Science.gov (United States)

    Silveira, Marcelle Moura; Oliveira, Thaís Larré; Schuch, Rodrigo Andrade; McBride, Alan John Alexander; Dellagostin, Odir Antônio; Hartwig, Daiane Drawanz

    2017-10-09

    Leptospirosis is an infectious disease caused by pathogenic Leptospira species. The vaccines that are currently available for leptospirosis are composed of whole-cell preparations and suffer from limitations such as low efficacy, multiple side-effects, poor immunological memory and lack of cross-protection against different serovars of Leptospira spp. In light of the global prevalence of this disease, the development of a more effective vaccine against leptospirosis is of paramount importance. Genetic immunization is a promising alternative to conventional vaccine development. In the last 25years, several novel strategies have been developed for increasing the efficacy of DNA vaccines. Examples of such strategies include the introduction of novel plasmid vectors, adjuvants, alternate delivery routes, and prime-boost regimens. Herein we discuss the latest and most promising advances that have been made in developing DNA vaccines against leptospirosis. We also deliberate over the future directions that must be undertaken in order to improve results in this field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Adapting to the global shortage of cholera vaccines: targeted single dose cholera vaccine in response to an outbreak in South Sudan.

    Science.gov (United States)

    Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Ciglenecki, Iza; Luquero, Francisco J; Azman, Andrew S; Cabrol, Jean-Clement

    2017-04-01

    Shortages of vaccines for epidemic diseases, such as cholera, meningitis, and yellow fever, have become common over the past decade, hampering efforts to control outbreaks through mass reactive vaccination campaigns. Additionally, various epidemiological, political, and logistical challenges, which are poorly documented in the literature, often lead to delays in reactive campaigns, ultimately reducing the effect of vaccination. In June 2015, a cholera outbreak occurred in Juba, South Sudan, and because of the global shortage of oral cholera vaccine, authorities were unable to secure sufficient doses to vaccinate the entire at-risk population-approximately 1 million people. In this Personal View, we document the first public health use of a reduced, single-dose regimen of oral cholera vaccine, and show the details of the decision-making process and timeline. We also make recommendations to help improve reactive vaccination campaigns against cholera, and discuss the importance of new and flexible context-specific dose regimens and vaccination strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs.

    Science.gov (United States)

    Alaoui, Lamine; Palomino, Gustavo; Zurawski, Sandy; Zurawski, Gerard; Coindre, Sixtine; Dereuddre-Bosquet, Nathalie; Lecuroux, Camille; Goujard, Cecile; Vaslin, Bruno; Bourgeois, Christine; Roques, Pierre; Le Grand, Roger; Lambotte, Olivier; Favier, Benoit

    2017-11-13

    Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.

  9. Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail

    Directory of Open Access Journals (Sweden)

    Takeo eKuwata

    2013-05-01

    Full Text Available The role of antibodies in protecting the host from human immunodeficiency virus type 1 (HIV-1 infection is of considerable interest, particularly because the RV144 trial results suggest that antibodies contribute to protection. Although infection of nonhuman primates with simian immunodeficiency virus (SIV is commonly used as an animal model of HIV-1 infection, the viral epitopes that elicit potent and broad neutralizing antibodies to SIV have not been identified. We isolated a monoclonal antibody (MAb B404 that potently and broadly neutralizes various SIV strains. B404 targets a conformational epitope comprising the V3 and V4 loops of Env that intensely exposed when Env binds CD4. B404-resistant variants were obtained by passaging viruses in the presence of increasing concentration of B404 in PM1/CCR5 cells. Genetic analysis revealed that the Q733stop mutation, which truncates the cytoplasmic tail of gp41, was the first major substitution in Env during passage. The maximal inhibition by B404 and other MAbs were significantly decreased against a recombinant virus with a gp41 truncation compared with the parental SIVmac316. This indicates that the gp41 truncation was associated with resistance to antibody-mediated neutralization. The infectivities of the recombinant virus with the gp41 truncation were 7900-fold, 1000-fold, and 140-fold higher than those of SIVmac316 in PM1, PM1/CCR5, and TZM-bl cells, respectively. Immunoblotting analysis revealed that the gp41 truncation enhanced the incorporation of Env into virions. The effect of the gp41 truncation on infectivity was not obvious in the HSC-F macaque cell line, although the resistance of viruses harboring the gp41 truncation to neutralization was maintained. These results suggest that viruses with a truncated gp41 cytoplasmic tail were selected by increased infectivity in human cells and by acquiring resistance to neutralizing antibody.

  10. Organic contaminants degradation from the S(IV) autoxidation process catalyzed by ferrous-manganous ions: A noticeable Mn(III) oxidation process.

    Science.gov (United States)

    Zhang, Jiaming; Ma, Jun; Song, Haoran; Sun, Shaofang; Zhang, Zhongxiang; Yang, Tao

    2018-04-15

    Remarkable atrazine degradation in the S(IV) autoxidation process catalyzed by Fe 2+ -Mn 2+ (Fe 2+ /Mn 2+ /sulfite) was demonstrated in this study. Competitive kinetic experiments, alcohol inhibiting methods and electron spin resonance (ESR) experiments proved that sulfur radicals were not the major oxidation species. Mn(III) was demonstrated to be the primary active species in the Fe 2+ /Mn 2+ /sulfite process based on the comparison of oxidation selectivity. Moreover, the inhibiting effect of the Mn(III) hydrolysis and the S(IV) autoxidation in the presence of organic contaminants indicated the existence of three Mn(III) consumption routes in the Fe 2+ /Mn 2+ /sulfite process. The absence of hydroxyl radical and sulfate radical was interpreted by the competitive dynamics method. The oxidation capacity of the Fe 2+ /Mn 2+ /sulfite was independent of the initial pH (4.0-6.0) because the fast decay of S(IV) decreased initial pH below 4.0 rapidly. The rate of ATZ degradation was independent of the dissolved oxygen (DO) because that the major DO consumption process was not the rate determining step during the production of SO 5 •- . Phosphate and bicarbonate were confirmed to have greater inhibitory effects than other environmental factors because of their strong pH buffering capacity and complexing capacity for Fe 3+ . The proposed acetylation degradation pathway of ATZ showed the application of the Fe 2+ /Mn 2+ /sulfite process in the research of contaminants degradation pathways. This work investigated the characteristics of the Fe 2+ /Mn 2+ /sulfite process in the presence of organic contaminants, which might promote the development of Mn(III) oxidation technology. Copyright © 2018. Published by Elsevier Ltd.

  11. Factors associated with the success of rabies vaccination of dogs in Sweden

    Directory of Open Access Journals (Sweden)

    Rivera Esteban

    2011-03-01

    Full Text Available Abstract Background United Kingdom, Ireland, Malta and Sweden maintain their national provisions for a transitional period regarding rules concerning rabies vaccination and individual serological test for rabies neutralizing antibodies. The purpose of vaccinating dogs against rabies is to establish pre-exposure immunity and protect individual animals from contracting rabies. The aim of the study was to investigate factors associated with reaching the internationally accepted threshold antibody titre of 0.5 IU/mL after rabies vaccination of dogs. Methods The study was a prospective single cohort study including 6,789 samples from Swedish dogs vaccinated with commercially available vaccines in Sweden, and the dog's antibody responses were determined by the OIE approved FAVN test. Information on potential risk factors; breed, age, gender, date of vaccination, vaccine label and the number of vaccinations, was collected for each dog. Associations between the dependent variable, serological response ≥ 0.5 IU/mL or Results Of 6,789 vaccinated dogs, 6,241 (91.9% had an approved test result of ≥ 0.5 IU/mL. The results of the multivariable logistic regression analysis showed that vaccinating with vaccine B reduced the risk of having antibody titres of 5 years of age to have antibody titres of Conclusions The probability of success of rabies vaccinations of dogs depends on type of vaccine used, number of rabies vaccinations, the breed size of the dog, age at vaccination, and number of days after vaccination when the antibody titres are tested. The need for a booster vaccination regimen is recommended for larger breeds of dog.

  12. 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 ...

  13. Vaccines and Pregnancy

    Science.gov (United States)

    ... vaccination. Because it is very unlikely that a live vaccine will cause disease, being in the same household with a healthy child who has received a live vaccine is also not likely to increase the ...

  14. 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....

  15. Vaccines and Thimerosal

    Science.gov (United States)

    ... this? Submit What's this? Submit Button Thimerosal in Vaccines Recommend on Facebook Tweet Share Compartir Thimerosal is ... harm. Thimerosal prevents the growth of bacteria in vaccines. Thimerosal is added to vials of vaccine that ...

  16. Vaccines Stop Illness

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Vaccines Stop Illness Past Issues / Spring 2008 Table of ... meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about vaccine ...

  17. Childhood Vaccine Schedule

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Childhood Vaccine Schedule Past Issues / Spring 2008 Table of Contents ... please turn Javascript on. When to Vaccinate What Vaccine Why Birth (or any age if not previously ...

  18. Vaccines Stop Illness

    Science.gov (United States)

    ... page please turn JavaScript on. Feature: Diseases and Vaccinations Vaccines Stop Illness Past Issues / Spring 2015 Table ... if we take away the protection given by vaccination, more and more people will be infected and ...

  19. Pertussis (Whooping Cough) Vaccination

    Science.gov (United States)

    ... Tetanus-diphtheria-acellular Pertussis vaccine Whooping Cough (Pertussis) Vaccination Pronounced (per-TUS-iss) Recommend on Facebook Tweet ... and adults receive Tdap. CDC recommends whooping cough vaccination for all babies and children, preteens and teens, ...

  20. 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 ( ...

  1. Vaccine refrigeration

    Science.gov (United States)

    McColloster, Patrick J; Martin-de-Nicolas, Andres

    2014-01-01

    This commentary reviews recent changes in Centers for Disease Control (CDC) vaccine storage guidelines that were developed in response to an investigative report by the Office of the Inspector General. The use of temperature data loggers with probes residing in glycol vials is advised along with storing vaccines in pharmaceutical refrigerators. These refrigerators provide good thermal distribution but can warm to 8 °C in less than one hour after the power is discontinued. Consequently, electric grid instability influences appropriate refrigerator selection and the need for power back-up. System Average Interruption Duration Index (SAIDI) values quantify this instability and can be used to formulate region-specific guidelines. A novel aftermarket refrigerator regulator with a battery back-up power supply and microprocessor control system is also described. PMID:24442209

  2. Lack of impact of rotavirus vaccines on seizure-related hospitalizations in children under 5 years old in Spain.

    Science.gov (United States)

    Orrico-Sánchez, Alejandro; López-Lacort, Mónica; Muñoz-Quiles, Cintia; Díez-Domingo, Javier

    2018-02-02

    Up to date the impact of rotavirus (RV) vaccines on seizures has been poorly evaluated, with some studies but not all, showing different degrees of protection. To assess the impact of RV vaccines on convulsions-related hospitalizations among children under 5 years of age residing in the Region of Valencia, Spain. A population-based, ecological study using the hospital discharge record (MBDS), the population-based administrative database (SIP) and the vaccine register (SIV), among Valencia Region's children <5 years old, during 2003 - 2015. Impact of vaccination on seizures-related hospitalization rates (780.3* ICD-9-MC code) was estimated by a multivariate Bayesian mixed Poisson regression model. Since RV vaccines licensure in 2007, its coverage rate increased up to around 42%. When the impact of vaccination against seizures was controlled for potential confounders in the multivariate analysis, there was a non-statistically significant protective effect. We could not find any impact of RV vaccine coverage on seizure-related hospitalizations in children <5 years.

  3. Neighborhood-targeted and case-triggered use of a single dose of oral cholera vaccine in an urban setting: Feasibility and vaccine coverage.

    Science.gov (United States)

    Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Muller, Vincent; Llosa, Augusto E; Uzzeni, Florent; Luquero, Francisco J; Ciglenecki, Iza; Azman, Andrew S

    2017-06-01

    In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3). Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

  4. Engineered human vaccines

    Energy Technology Data Exchange (ETDEWEB)

    Sandhu, J.S. (Mount Sinai Hospital, Toronto, Ontario (Canada). Div. of Immunology and Neurobiology)

    1994-01-01

    The limitations of human vaccines in use at present and the design requirements for a new generation of human vaccines are discussed. The progress in engineering of human vaccines for bacteria, viruses, parasites, and cancer is reviewed, and the data from human studies with the engineered vaccines are discussed, especially for cancer and AIDS vaccines. The final section of the review deals with the possible future developments in the field of engineered human vaccines and the requirement for effective new human adjuvants.

  5. Effective Vaccination Policies

    Science.gov (United States)

    2010-03-31

    effective” vaccine can stop the virus spread by causing herd immunity and the disease will die out. Vaccines that have this capability are in the vaccine ...Effective Vaccination Policies L. Shawa, W. Spears∗,b, L. Billingsc, P. Maximd aDepartment of Computer Science, University of Wyoming, Laramie, WY...this study is to develop tools that determine the optimal distribution of a vaccine supply in the model. Using plausible benchmark vaccine allocation

  6. Schistosomiasis vaccines

    OpenAIRE

    Siddiqui, Afzal A.; Siddiqui, Bilal A.; Ganley-Leal, Lisa

    2011-01-01

    Schistosomiasis is a major neglected tropical disease of public health importance to a billion people. An estimated 200 million people are currently infected; an additional 779 million individuals are at risk to acquire the infection in 74 countries. Despite many years of implementation of mass anti-parasitic drug therapy programs and other control measures, this disease has not been contained and continues to spread to new geographic areas.  The discovery of a protective vaccine still remain...

  7. Abstractive Summarization of Drug Dosage Regimens for Supporting Drug Comparison.

    Science.gov (United States)

    Ugon, Adrien; Berthelot, Hélène; Venot, Alain; Favre, Madeleine; Duclos, Catherine; Lamy, Jean-Baptiste

    2015-01-01

    Complicated dosage regimens often reduce adherence to drug treatments. The ease-of-administration must thus be taken into account when prescribing. Given one drug, there exists often several dosage regimens. Hence, comparison to similar drugs is difficult. Simplifying and summarizing them appears to be a required task for supporting General Practitioners to find the drug with the simplest regimen for the patient. We propose a summarization in two steps: first prunes out all low-importance information, and second proceed to fusion of remaining information. Rules for pruning and fusion strategies were designed by an expert in drug models. Evaluation was conducted on a dataset of 169 drugs. The agreement rate was 27.2%. We demonstrate that applying rules leads to a result that is correct by a computational point of view, but the result is often meaningless for the GP. We conclude with recommendations for further work.

  8. Utilization and evaluation of noncore chemotherapy regimens within an academic medical center.

    Science.gov (United States)

    Jared, Jason R; Mably, Mary S; Makielski, Rory; Reed, Michael P; Fallon, Michael J; Liu, Glenn; Mulkerin, Daniel; Callander, Natalie S

    2017-10-01

    Uniformity of evidence-based chemotherapy prescribing using approved, standard, or "core" regimens provides systems-based safety. Noncore chemotherapy regimens are non-standard-of-care regimens requested by physicians on a patient-by-patient basis. Chemotherapy Council, a Pharmacy & Therapeutics subcommittee, assesses all requests and determines approval status based upon submitted evidence and patient-specific factors. This study's purpose is to describe noncore chemotherapy regimens utilization, efficacy, and clinical outcomes in patients receiving noncore chemotherapy regimens. This retrospective chart review includes a two-stage utilization and outcomes evaluation of patients receiving noncore chemotherapy regimens. Stage I, a demographics and utilization assessment of patients receiving noncore chemotherapy regimens, has data collection including patient age, sex, performance score, malignancy, and noncore chemotherapy regimen use justification. Stage II assesses noncore chemotherapy regimen-related, patient-specific outcomes of breast cancer noncore chemotherapy regimen patients. Breast cancer patients were evaluated on regimen and clinical outcomes including disease stage, regimen duration, discontinuation reason, subsequent chemotherapy, survival, and time from noncore chemotherapy regimen until death. Within stage I, 307 patient-specific noncore chemotherapy regimen requests were submitted. The most commonly submitted rationale was modification of a core regimen (33%), followed by patient-specific factors (29%) and salvage therapy (22%). For stage II, 29 breast cancer patients received a noncore chemotherapy regimen and most (54%) received a modified core regimen. The vast majority of noncore chemotherapy regimen discontinuation was due to either regimen completion (42%) or disease progression (42%). Nonelective hospitalizations (35%) and mortality (30%) were found during the median 13.3 months of follow up. Noncore chemotherapy regimen use provides

  9. Applying optimization algorithms to tuberculosis antibiotic treatment regimens.

    Science.gov (United States)

    Cicchese, Joseph M; Pienaar, Elsje; Kirschner, Denise E; Linderman, Jennifer J

    2017-12-01

    Tuberculosis (TB), one of the most common infectious diseases, requires treatment with multiple antibiotics taken over at least 6 months. This long treatment often results in poor patient-adherence, which can lead to the emergence of multi-drug resistant TB. New antibiotic treatment strategies are sorely needed. New antibiotics are being developed or repurposed to treat TB, but as there are numerous potential antibiotics, dosing sizes and potential schedules, the regimen design space for new treatments is too large to search exhaustively. Here we propose a method that combines an agent-based multi-scale model capturing TB granuloma formation with algorithms for mathematical optimization to identify optimal TB treatment regimens. We define two different single-antibiotic treatments to compare the efficiency and accuracy in predicting optimal treatment regimens of two optimization algorithms: genetic algorithms (GA) and surrogate-assisted optimization through radial basis function (RBF) networks. We also illustrate the use of RBF networks to optimize double-antibiotic treatments. We found that while GAs can locate optimal treatment regimens more accurately, RBF networks provide a more practical strategy to TB treatment optimization with fewer simulations, and successfully estimated optimal double-antibiotic treatment regimens. Our results indicate surrogate-assisted optimization can locate optimal TB treatment regimens from a larger set of antibiotics, doses and schedules, and could be applied to solve optimization problems in other areas of research using systems biology approaches. Our findings have important implications for the treatment of diseases like TB that have lengthy protocols or for any disease that requires multiple drugs.

  10. Characteristics of HIV antiretroviral regimen and treatment adherence

    Directory of Open Access Journals (Sweden)

    Vera Lúcia da Silveira

    Full Text Available The relationship between characteristics of HIV antiretroviral regimens and treatment adherence was studied in adolescent and adult patients who underwent antiretroviral therapy from January 1998 to September 2000, at the Service for Specialized Assistance in Pelotas. The patients were interviewed on two occasions, and the use of antiretrovirals during the previous 48 hours was investigated by a self-report. Adherence was defined as use of 95% or more of the prescribed medication. Social-demographic variables were collected through direct questionnaires. The antiretroviral regimen and clinical data were copied from the patients' records. Associations between the independent variables and adherence were analyzed by means of logistic regression. The multivariate analysis included characteristics of the antiretroviral regimens, social-demographic variables, as well as perception of negative effects, negative physiological states, and adverse effects of the treatment. Among the 224 selected patients, 194 participated in our study. Their ages varied from 17 to 67 years; most patients were men, with few years of schooling and a low family income. Only 49% adhered to the treatment. Adherence to treatment regimens was reduced when more daily doses were indicated: three to four doses (odds ratio of adherence to treatment (OR=0.47, 95% confidence interval (CI 0.22-1.01 and five to six (OR=0.24, 95% CI 0.09-0.62; two or more doses taken in a fasting state (OR=0.59, 95% CI 0.11-0.68, and for patients who reported adverse effects to the treatment (OR=0.39, 95% CI 0.19-0.77. Most of the regimens with more than two daily doses of medication included at least one dose apart from mealtimes. The results suggest that, if possible, regimens with a reduced number of doses should be chosen, with no compulsory fasting, and with few adverse effects. Strategies to minimize these effects should be discussed with the patients.

  11. Immunology Update: New Vaccines.

    Science.gov (United States)

    Starr, S Paul

    2016-11-01

    A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  12. Hepatitis B Vaccine

    Science.gov (United States)

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

  13. Development of replication-deficient adenovirus malaria vaccines.

    Science.gov (United States)

    Hollingdale, Michael R; Sedegah, Martha; Limbach, Keith

    2017-03-01

    Malaria remains a major threat to endemic populations and travelers, including military personnel to these areas. A malaria vaccine is feasible, as radiation attenuated sporozoites induce nearly 100% efficacy. Areas covered: This review covers current malaria clinical trials using adenoviruses and pre-clinical research. Heterologous prime-boost regimens, including replication-deficient human adenovirus 5 (HuAd5) carrying malaria antigens, are efficacious. However, efficacy appears to be adversely affected by pre-existing anti-HuAd5 antibodies. Current strategies focus on replacing HuAd5 with rarer human adenoviruses or adenoviruses isolated from non-human primates (NHPs). The chimpanzee adenovirus ChAd63 is undergoing evaluation in clinical trials including infants in malaria-endemic areas. Key antigens have been identified and are being used alone, in combination, or with protein subunit vaccines. Gorilla adenoviruses carrying malaria antigens are also currently being evaluated in preclinical models. These replacement adenovirus vectors will be successfully used to develop vaccines against malaria, as well as other infectious diseases. Expert commentary: Simplified prime-boost single shot regimens, dry-coated live vector vaccines or silicon microneedle arrays could be developed for malaria or other vaccines. Replacement vectors with similar or superior immunogenicity have rapidly advanced, and several are now in extensive Phase 2 and beyond in malaria as well as other diseases, notably Ebola.

  14. Optimised electroporation mediated DNA vaccination for treatment of prostate cancer.

    LENUS (Irish Health Repository)

    Ahmad, Sarfraz

    2010-01-01

    ABSTRACT: BACKGROUND: Immunological therapies enhance the ability of the immune system to recognise and destroy cancer cells via selective killing mechanisms. DNA vaccines have potential to activate the immune system against specific antigens, with accompanying potent immunological adjuvant effects from unmethylated CpG motifs as on prokaryotic DNA. We investigated an electroporation driven plasmid DNA vaccination strategy in animal models for treatment of prostate cancer. METHODS: Plasmid expressing human PSA gene (phPSA) was delivered in vivo by intra-muscular electroporation, to induce effective anti-tumour immune responses against prostate antigen expressing tumours. Groups of male C57 BL\\/6 mice received intra-muscular injections of phPSA plasmid. For phPSA delivery, quadriceps muscle was injected with 50 mug plasmid. After 80 seconds, square-wave pulses were administered in sequence using a custom designed pulse generator and acustom-designed applicator with 2 needles placed through the skin central to the muscle. To determine an optimum treatment regimen, three different vaccination schedules were investigated. In a separate experiment, the immune potential of the phPSA vaccine was further enhanced with co- administration of synthetic CpG rich oligonucleotides. One week after last vaccination, the mice were challenged subcutaneously with TRAMPC1\\/hPSA (prostate cancer cell line stably expressing human PSA) and tumour growth was monitored. Serum from animals was examined by ELISA for anti-hPSA antibodies and for IFNgamma. Histological assessment of the tumours was also carried out. In vivo and in vitro cytotoxicity assays were performed with splenocytes from treated mice. RESULTS: The phPSA vaccine therapy significantly delayed the appearance of tumours and resulted in prolonged survival of the animals. Four-dose vaccination regimen provided optimal immunological effects. Co - administration of the synthetic CpG with phPSA increased anti-tumour responses

  15. Considerations for Oral Cholera Vaccine Use during Outbreak after Earthquake in Haiti, 2010−2011

    Science.gov (United States)

    Vicari, Andrea; Hyde, Terri B.; Mintz, Eric; Danovaro-Holliday, M. Carolina; Henry, Ariel; Tappero, Jordan W.; Roels, Thierry H.; Abrams, Joseph; Burkholder, Brenton T.; Ruiz-Matus, Cuauhtémoc; Andrus, Jon; Dietz, Vance

    2011-01-01

    Oral cholera vaccines (OCVs) have been recommended in cholera-endemic settings and preemptively during outbreaks and complex emergencies. However, experience and guidelines for reactive use after an outbreak has started are limited. In 2010, after over a century without epidemic cholera, an outbreak was reported in Haiti after an earthquake. As intensive nonvaccine cholera control measures were initiated, the feasibility of OCV use was considered. We reviewed OCV characteristics and recommendations for their use and assessed global vaccine availability and capacity to implement a vaccination campaign. Real-time modeling was conducted to estimate vaccine impact. Ultimately, cholera vaccination was not implemented because of limited vaccine availability, complex logistical and operational challenges of a multidose regimen, and obstacles to conducting a campaign in a setting with population displacement and civil unrest. Use of OCVs is an option for cholera control; guidelines for their appropriate use in epidemic and emergency settings are urgently needed. PMID:22099114

  16. [Vaccination in the elderly].

    Science.gov (United States)

    Kwetkat, A; Pletz, M W

    2013-10-01

    The aging immune system, so-called immunosenescence, is well documented as the cause of increased infection rates and severe, often complicated course of infections in the elderly with increased morbidity and mortality rates. Furthermore, it can lead to decreased efficacy of vaccination. The administration of more immunogenic vaccines can be beneficial in the elderly. Implementing vaccination recommendations for the elderly by STIKO can reduce burden of infectious diseases by prevention of infection or reduction of severity of infection. The following vaccinations are recommended by STIKO for all persons aged 60 and above: annual influenza vaccination (additionally all nursing home residents independently of age), once only pneumococcal polysaccharide vaccination, completion of tetanus and diphtheria (Td) vaccination as well as regular revaccination. All adults should be vaccinated against pertussis with Tdap vaccine once. Meanwhile, pneumococcal conjugate vaccine is allowed for administration in adults but is not recommended by STIKO yet. A lifelong course of vaccination may help to attenuate the effect of immunosenescence.

  17. Complex assembly, crystallization and preliminary X-ray crystallographic studies of rhesus macaque MHC Mamu-A*01 complexed with an immunodominant SIV-Gag nonapeptide

    International Nuclear Information System (INIS)

    Chu, Fuliang; Lou, Zhiyong; Gao, Bin; Bell, John I.; Rao, Zihe; Gao, George F.

    2005-01-01

    Crystallization of the first rhesus macaque MHC class I complex. Simian immunodeficiency virus (SIV) infection in rhesus macaques has been used as the best model for the study of human immunodeficiency virus (HIV) infection in humans, especially in the cytotoxic T-lymphocyte (CTL) response. However, the structure of rhesus macaque (or any other monkey model) major histocompatibility complex class I (MHC I) presenting a specific peptide (the ligand for CTL) has not yet been elucidated. Here, using in vitro refolding, the preparation of the complex of the rhesus macaque MHC I allele (Mamu-A*01) with human β 2 m and an immunodominant peptide, CTPYDINQM (Gag-CM9), derived from SIV Gag protein is reported. The complex (45 kDa) was crystallized; the crystal belongs to space group I422, with unit-cell parameters a = b = 183.8, c = 155.2 Å. The crystal contains two molecules in the asymmetric unit and diffracts X-rays to 2.8 Å resolution. The structure is being solved by molecular replacement and this is the first attempt to determined the crystal structure of a peptide–nonhuman primate MHC complex

  18. Combined single-cell quantitation of host and SIV genes and proteins ex vivo reveals host-pathogen interactions in individual cells.

    Directory of Open Access Journals (Sweden)

    Diane L Bolton

    2017-06-01

    Full Text Available CD4 T cells harboring HIV-1/SIV represent a formidable hurdle to eradicating infection, and yet their detailed phenotype remains unknown. Here we integrate two single-cell technologies, flow cytometry and highly multiplexed quantitative RT-PCR, to characterize SIV-infected CD4 T cells directly ex vivo. Within individual cells, we correlate the cellular phenotype, in terms of host protein and RNA expression, with stages of the viral life cycle defined by combinatorial expression of viral RNAs. Spliced RNA+ infected cells display multiple memory and activation phenotypes, indicating virus production by diverse CD4 T cell subsets. In most (but not all cells, progressive infection accompanies post-transcriptional downregulation of CD4 protein, while surface MHC class I is largely retained. Interferon-stimulated genes were also commonly upregulated. Thus, we demonstrate that combined quantitation of transcriptional and post-transcriptional regulation at the single-cell level informs in vivo mechanisms of viral replication and immune evasion.

  19. Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

    Directory of Open Access Journals (Sweden)

    Balk JM

    2015-08-01

    Full Text Available Jiska M Balk,1 Guido RMM Haenen,1 Özgür M Koc,2 Ron Peters,3 Aalt Bast,1 Wim JF van der Vijgh,1 Ger H Koek,4 1Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, 2Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 3DSM Resolve, Geleen, 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: The combination of ribavirin (RBV and pegylated interferon (PEG-IFN is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods: In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results: Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose was significantly different between the two groups (P>0.05. Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0

  20. Intradermal vaccination against hepatitis B in a group of medical ...

    African Journals Online (AJOL)

    A prospective study of a low-dose (one-tenth) intradermal regimen using recombinant hepatitis B vaccine was under- taken during two consecutive years in 4th-year medical stu- dents. Eightj;one per cent of the vaccinees (123/152) sero- converted with anti.HBs levels of> 10 lUll. The lower titre of hepatitis B surface ...

  1. Humoral response to 2 inactivated bluetongue virus serotype-8 vaccines in South American camelids.

    Science.gov (United States)

    Zanolari, P; Bruckner, L; Fricker, R; Kaufmann, C; Mudry, M; Griot, C; Meylan, M

    2010-01-01

    Bluetongue virus serotype 8 (BTV-8) has caused disease in domestic ruminants in several countries of northern Europe since 2006. In 2008 a mass-vaccination program was launched in most affected countries using whole virus inactivated vaccines. To evaluate 2 inactivated vaccines (Bovilis BTV 8; BTVPUR AlSap8) for immunogenicity and safety against BTV-8 in South American camelids (SAC) in a field trial. Forty-two SAC (25 Alpacas, 17 Llamas) aged between 1 and 16 years. The animals were vaccinated twice at intervals of 21 days. They were observed clinically for adverse local, systemic, or both reactions throughout the trial. Blood samples collected on days 0, 14, 21, 43, and 156 after vaccination were tested for the presence of BTV-8 virus by real time-polymerase chain reaction and of specific antibodies by competitive ELISA and a serum neutralization test. All vaccinated animals developed antibodies to BTV-8 after the 2nd administration of the vaccine. No adverse effects were observed except for moderate local swellings at the injection site, which disappeared within 21 days. Slightly increased body temperatures were only observed in the first 2 days after vaccination. The BTV was not detected in any of the samples analyzed. The administration of the 2 inactivated commercial vaccines was safe and induced seroconversion against BTV-8 in all vaccinated animals. The results of this study suggest that 2 doses injected 3 weeks apart is a suitable vaccination regimen for SAC.

  2. 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

  3. What to Start: Selecting a First HIV Regimen

    Science.gov (United States)

    ... CCR5 antagonists Integrase strand transfer inhibitors (INSTIs) Post-attachment inhibitors In general, a person's first HIV regimen includes two NRTIs plus an INSTI, an NNRTI, or a PI boosted with cobicistat (brand name: Tybost) or ritonavir (brand name: Norvir). Cobicistat ...

  4. Assessment of non-standard HIV antiretroviral therapy regimens at ...

    African Journals Online (AJOL)

    2016-03-06

    Mar 6, 2016 ... Aim. Lighthouse Trust in Lilongwe, Malawi serves approximately 25,000 patients with HIV antiretroviral therapy (ART) regimens standardized according to national treatment guidelines. However, as a referral centre for complex cases, Lighthouse Trust occasionally treats patients with non-standard ART.

  5. Effects of different penning conditions, feeding regimens and season ...

    African Journals Online (AJOL)

    The pigs were randomly allocated to three feeding regimens, a controlled single feeding, ad libitum single feeding and ad libitum group feeding, with six animals per ad libitum group. This resulted in 96 pigs in six treatments with six replicates. The diets were high (HF) and low (LF) nutrient dense feeds, where the LF was ...

  6. Comparison of different insulin regimens in elderly patients with NIDDM

    NARCIS (Netherlands)

    Wolffenbuttel, B H; Sels, J P; Rondas-Colbers, G J; Menheere, P P; Nieuwenhuijzen Kruseman, A C

    1996-01-01

    OBJECTIVE: To compare the metabolic effects of three different frequently used regimens of insulin administration on blood glucose control and serum lipids, and the costs associated with this treatment, in subjects with NIDDM, who were poorly controlled with oral antihyperglycemic agents. RESEARCH

  7. Randomization of two dosing regimens of vaginal misoprostol for ...

    African Journals Online (AJOL)

    Objectives: To compare the effectiveness of two dosing regimens of vaginal misoprostol for cervical ripening and induction of labour. Materials and Methods: Pregnant women with singleton low risk pregnancy at term scheduled for elective induction of labour were randomized to receive either 25 µg or 50 µg of vaginal ...

  8. Efficacy of Some Combination Regimens of Oral Hypoglycaemic ...

    African Journals Online (AJOL)

    Purpose: To examine the efficacy of selected oral hypoglycaemic agent (OHA) regimens in a small group of patients receiving such treatment. Methods: This was a retrospective, observational study that involved patients who had been diagnosed with type 2 diabetes mellitus and undergoing routine follow-up at a teaching ...

  9. The liberal peace security regimen: a gramscian critique of its ...

    African Journals Online (AJOL)

    Current security regimens are grounded in the advancement of liberal peace. All inter-governmental organizations, most states and most donor agencies more or less accept as common sense the self-evident virtuosity and truth of the liberal peace project. However, there is a profound contradiction within this project in ...

  10. mtct regimen choice, drug resistance and the treatment of hiv

    African Journals Online (AJOL)

    drug-resistant variants may become selected as long as the drug is administered. There has been some concern that the use of ARV monotherapy for the prevention of MTCT, including ... potential implications for perinatal transmission, the choice of ... transmission rate using this regimen, short-term treatment with dual ...

  11. Assessment of non-standard HIV antiretroviral therapy regimens at ...

    African Journals Online (AJOL)

    2016-03-06

    Mar 6, 2016 ... guidelines for children and not adults. Discussion. Less than 1% of the 17,000 patients receiving ART for treatment of HIV at Lighthouse Trust in 2012 were being treated with NS-ART, signifying a strong adherence to standardized regimens by clinicians. Assessing the reasons for use of NS-ART is essential ...

  12. outcome and haemato-toxicity of two chemotherapy regimens for ...

    African Journals Online (AJOL)

    2009-12-02

    Dec 2, 2009 ... enhancement of bone marrow toxicity and inability to provide necessary .... Consolidation (2 courses 7-10 days apart). - adriamycin ... study cases. Follow up period ranged between one and 18 months with a median of seven months from time of diagnosis. In the short course regimen, 58.3% presented with ...

  13. mtct regimen choice, drug resistance and the treatment of hiv

    African Journals Online (AJOL)

    Perinauzl HW Unit, University ofcJu WilWalmTand. MTCT REGIMEN CHOICE, DRUG. RESISTANCE AND THE TREATMENT OF. HIV-I-INFECTED CHILDREN assessing ARV drug resistance. Genotypic assays detect specific point mutations in the HIV genome that are associated with phenotypic resistance. These are most.

  14. Gonzalez Regimen (PDQ®)—Health Professional Version

    Science.gov (United States)

    The Gonzalez regimen is a specialized diet that uses enzymes, supplements, and other factors in cancer management. It is based on a theory that involves the use of pancreatic enzymes to help the body get rid of toxins that lead to cancer. Read about existing clinical data in this expert-reviewed summary.

  15. Subtype C gp140 Vaccine Boosts Immune Responses Primed by the South African AIDS Vaccine Initiative DNA-C2 and MVA-C HIV Vaccines after More than a 2-Year Gap.

    Science.gov (United States)

    Gray, Glenda E; Mayer, Kenneth H; Elizaga, Marnie L; Bekker, Linda-Gail; Allen, Mary; Morris, Lynn; Montefiori, David; De Rosa, Stephen C; Sato, Alicia; Gu, Niya; Tomaras, Georgia D; Tucker, Timothy; Barnett, Susan W; Mkhize, Nonhlanhla N; Shen, Xiaoying; Downing, Katrina; Williamson, Carolyn; Pensiero, Michael; Corey, Lawrence; Williamson, Anna-Lise

    2016-06-01

    A phase I safety and immunogenicity study investigated South African AIDS Vaccine Initiative (SAAVI) HIV-1 subtype C (HIV-1C) DNA vaccine encoding Gag-RT-Tat-Nef and gp150, boosted with modified vaccinia Ankara (MVA) expressing matched antigens. Following the finding of partial protective efficacy in the RV144 HIV vaccine efficacy trial, a protein boost with HIV-1 subtype C V2-deleted gp140 with MF59 was added to the regimen. A total of 48 participants (12 U.S. participants and 36 Republic of South Africa [RSA] participants) were randomized to receive 3 intramuscular (i.m.) doses of SAAVI DNA-C2 of 4 mg (months 0, 1, and 2) and 2 i.m. doses of SAAVI MVA-C of 1.45 × 10(9) PFU (months 4 and 5) (n = 40) or of a placebo (n = 8). Approximately 2 years after vaccination, 27 participants were rerandomized to receive gp140/MF59 at 100 μg or placebo, as 2 i.m. injections, 3 months apart. The vaccine regimen was safe and well tolerated. After the DNA-MVA regimen, CD4(+) T-cell and CD8(+) T-cell responses occurred in 74% and 32% of the participants, respectively. The protein boost increased CD4(+) T-cell responses to 87% of the subjects. All participants developed tier 1 HIV-1C neutralizing antibody responses as well as durable Env binding antibodies that recognized linear V3 and C5 peptides. The HIV-1 subtype C DNA-MVA vaccine regimen showed promising cellular immunogenicity. Boosting with gp140/MF59 enhanced levels of binding and neutralizing antibodies as well as CD4(+) T-cell responses to HIV-1 envelope. (This study has been registered at ClinicalTrials.gov under registration no. NCT00574600 and NCT01423825.). Copyright © 2016 Gray et al.

  16. Vaccination in food allergic patients

    African Journals Online (AJOL)

    allergy: • Vaccines produced in embryonated eggs, such as yellow fever vaccine, influenza vaccine and rabies vaccine. Yellow fever vaccine is most likely to contain significant amounts of egg protein. • Vaccines produced in chick fibroblast cell cultures, such as measles and measles-mumps-rubella (MMR) vaccines, do not.

  17. VACCINATION SAFETY: MODERN DATA

    Directory of Open Access Journals (Sweden)

    V.К. Tatochenko

    2007-01-01

    Full Text Available Vaccination aided disease control over infection pathology among the children led to elimination of smallpox and poliomyelitis, drastic decrease of the tuberculous meningitis recurrences, tetanus, measles and other infection diseases and their complications. At the same time, Russia is still afraid to apply certain vaccines. The reasons for that are mainly subjective. This is the unjustified caution related to the fear that it may cause severe vaccine associated complications. The data in view of the lecture indicates the safety of the vaccinal prevention procedures and measures for the prevention of their complications.Key words: vaccinal prevention, vaccination complications, vaccination safety, children.

  18. Pros, cons, and ethics of HPV vaccine in teens-Why such controversy?

    Science.gov (United States)

    White, Mark Donald

    2014-12-01

    Human papillomavirus (HPV) infection remains one of the most commonly sexually transmitted infections in both females and males. HPV viruses are associated with several manifestations including genital warts, but more importantly for urology practitioners, cervical and penile carcinomas and recurrent genital condylomata in both sexes. The incidence of HPV-related carcinomas has increased in cervical, oropharyngeal, vulvar, penile, and anal cancers. Effective vaccines have been available for almost a decade, but widespread adoption of vaccine administration has been problematic for multiple reasons. Many countries (over 100) have adopted vaccine programs for females and an increasing number of countries are extending the indications to include males between the ages of 9-26. There still seems to be controversy surrounding these universal vaccination programs as well as some ethical and practical concerns regarding the administration of a vaccine for diseases that are associated with sexual contact in both sexes, especially during the early adolescent years. The objective was to provide a review of the available literature so pediatric and adult urologists may be more aware of the issues related to HPV vaccination in order to more effectively counsel patients and parents regarding the risks, benefits, and public health issues regarding HPV vaccination. This topic is especially relevant to pediatric urologists who see patients in the target age group for the HPV vaccine. There has been an explosion of literature regarding HPV vaccination programs and the relative difficulty in adopting the vaccine series with a completion rate of under 50% of patients in the recommended age ranges for vaccination. Articles were obtained from an extensive Medline literature search (1998-present) to evaluate the current HPV vaccination regimens for teenagers with special emphasis on the urologically focused disease burden. The adoption of universal HPV vaccination has been difficult

  19. Pros, cons, and ethics of HPV vaccine in teens—Why such controversy?

    Science.gov (United States)

    2014-01-01

    Introduction Human papillomavirus (HPV) infection remains one of the most commonly sexually transmitted infections in both females and males. HPV viruses are associated with several manifestations including genital warts, but more importantly for urology practitioners, cervical and penile carcinomas and recurrent genital condylomata in both sexes. The incidence of HPV-related carcinomas has increased in cervical, oropharyngeal, vulvar, penile, and anal cancers. Effective vaccines have been available for almost a decade, but widespread adoption of vaccine administration has been problematic for multiple reasons. Many countries (over 100) have adopted vaccine programs for females and an increasing number of countries are extending the indications to include males between the ages of 9-26. There still seems to be controversy surrounding these universal vaccination programs as well as some ethical and practical concerns regarding the administration of a vaccine for diseases that are associated with sexual contact in both sexes, especially during the early adolescent years. Objective The objective was to provide a review of the available literature so pediatric and adult urologists may be more aware of the issues related to HPV vaccination in order to more effectively counsel patients and parents regarding the risks, benefits, and public health issues regarding HPV vaccination. This topic is especially relevant to pediatric urologists who see patients in the target age group for the HPV vaccine. There has been an explosion of literature regarding HPV vaccination programs and the relative difficulty in adopting the vaccine series with a completion rate of under 50% of patients in the recommended age ranges for vaccination. Methods Articles were obtained from an extensive Medline literature search (1998-present) to evaluate the current HPV vaccination regimens for teenagers with special emphasis on the urologically focused disease burden. Results The adoption of universal

  20. Papillomavirus vaccine coverage and its determinants in South-Eastern France.

    Science.gov (United States)

    Lions, C; Pulcini, C; Verger, P

    2013-05-01

    We wanted: (i) to assess vaccine coverage (VC) for papillomavirus (HPV) (one and three doses of the vaccine, VC1 and VC3) and compliance with the recommended vaccination regimen (3rd dose within 1 year after the 1st dose) among 14-16 year-old girls; and (ii) to identify the factors independently associated with VC and compliance with the recommended vaccination regimen. We conducted a descriptive longitudinal study, using the National Health Insurance reimbursement database, for years 2007 to 2009, in South-Eastern France. We performed a multivariate analysis (Cox proportional hazards model). VC1 was 35.5%, with 68.8% of those who started vaccination having completed the 3-dose regimen, 64.1% within one year. VC1 and VC3 were positively associated with the girl's age. Girls covered by the complementary social welfare healthcare program and those living in rural areas had lower VC1 and VC3. Being covered by the complementary social welfare healthcare program was also associated with lower compliance with the recommended vaccination regimen. VC1 and VC3 were positively associated with the number of medical consultations during the study period. Important geographical variations were noted regarding VC1. Our study confirms that VC for HPV is insufficient in our region, and that there are socio-economic and geographical inequalities. Even though the vaccine is reimbursed for all girls, efforts must be made to improve VC, particularly for girls covered by the complementary social welfare healthcare program and those living in rural areas. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  1. 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.

  2. Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model.

    Science.gov (United States)

    Dunachie, Susanna; Berthoud, Tamara; Hill, Adrian V S; Fletcher, Helen A

    2015-09-29

    The complexity of immunity to malaria is well known, and clear correlates of protection against malaria have not been established. A better understanding of immune markers induced by candidate malaria vaccines would greatly enhance vaccine development, immunogenicity monitoring and estimation of vaccine efficacy in the field. We have previously reported complete or partial efficacy against experimental sporozoite challenge by several vaccine regimens in healthy malaria-naïve subjects in Oxford. These include a prime-boost regimen with RTS,S/AS02A and modified vaccinia virus Ankara (MVA) expressing the CSP antigen, and a DNA-prime, MVA-boost regimen expressing the ME TRAP antigens. Using samples from these trials we performed transcriptional profiling, allowing a global assessment of responses to vaccination. We used Human RefSeq8 Bead Chips from Illumina to examine gene expression using PBMC (peripheral blood mononuclear cells) from 16 human volunteers. To focus on antigen-specific changes, comparisons were made between PBMC stimulated with CSP or TRAP peptide pools and unstimulated PBMC post vaccination. We then correlated gene expression with protection against malaria in a human Plasmodium falciparum malaria challenge model. Differentially expressed genes induced by both vaccine regimens were predominantly in the IFN-γ pathway. Gene set enrichment analysis revealed antigen-specific effects on genes associated with IFN induction and proteasome modules after vaccination. Genes associated with IFN induction and antigen presentation modules were positively enriched in subjects with complete protection from malaria challenge, while genes associated with haemopoietic stem cells, regulatory monocytes and the myeloid lineage modules were negatively enriched in protected subjects. These results represent novel insights into the immune repertoires involved in malaria vaccination. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Immunogenicity of a reduced-dose whole killed rabies vaccine is significantly enhanced by ISCOMATRIX™ adjuvant, Merck amorphous aluminum hydroxylphosphate sulfate (MAA) or a synthetic TLR9 agonist in rhesus macaques.

    Science.gov (United States)

    DiStefano, Daniel; Antonello, Joseph M; Bett, Andrew J; Medi, Muneeswara B; Casimiro, Danilo R; ter Meulen, Jan

    2013-10-01

    There is a need for novel rabies vaccines suitable for short course, pre- and post-exposure prophylactic regimens which require reduced doses of antigen to address the current worldwide supply issue. We evaluated in rhesus macaques the immunogenicity of a quarter-dose of a standard rabies vaccine formulated with Merck's amorphous aluminum hydroxylphosphate sulfate adjuvant, the saponin-based ISCOMATRIX™ adjuvant, or a synthetic TLR9 agonist. All adjuvants significantly increased the magnitude and durability of the humoral immune response as measured by rapid fluorescent focus inhibition test (RFFIT). Several three-dose vaccine regimens resulted in adequate neutralizing antibody of ≥ 0.5 IU/ml earlier than the critical day seven post the first dose. Rabies vaccine with ISCOMATRIX™ adjuvant given at days 0 and 3 resulted in neutralizing antibody titers which developed faster and were up to one log10 higher compared to WHO-recommended intramuscular and intradermal regimens and furthermore, passive administration of human rabies immunoglobulin did not interfere with immunogenicity of this reduced dose, short course vaccine regimen. Adjuvantation of whole-killed rabies vaccine for intramuscular injection may therefore be a viable alternative to intradermal application of non-adjuvanted vaccine for both pre- and post-exposure regimens. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. [Efficacy of NO regimen and NP regimen on advanced non-small cell lung cancer: a prospective randomized trial].

    Science.gov (United States)

    Gao, Jian-Fei; Zhang, Xin-Hua; Wang, Jun; Rao, Zhi-Guo; Zhu, Yu-Ze; Ou, Wu-Ling; Zhang, Bi-Cheng; Du, Guang-Zu

    2005-08-01

    Oxaliplatin (LOHP) is an effective drug in treatment of non-small cell lung cancer (NSCLC) with mild toxicities to gastrointestinal tract, kidney, and bone marrow. Cisplatin (DDP) plus vinorelbine (NVB) constitute the first-line regimen (NP regimen) for NSCLC. This study was to compare the short-term response, long-term outcome, and adverse events between advanced NSCLC patients received NO regimen (LOHP plus NVB) and NP regimen. A total of 90 patients with advanced NSCLC were randomized into NO group (58 patients, 25 mg/m(2) of NVB, day 1 and day 8; 130 mg/m(2) of LOHP, day 1) and NP group (32 patients, 25 mg/m(2) of NVB, day 1 and day 8; 50 mg/m(2) of DDP, day 2 and day 3). The short-term response, long-term outcome, adverse events, and survival status of the 2 groups were observed. The response rates were 33.33% in NO group, and 35.48% in NP group, but no significant difference was detected between the 2 groups (P > 0.05). The clinical benefit response rate was significantly higher in NO group than in NP group (80.70% vs. 64.52%, P NP group; the median time of remission was 21 weeks in NO group, and 19 weeks in NP group; the median survival time was 39 weeks in NO group, and 37 weeks in NP group; the 1-year survival rate was 37.93% in NO group, and 31.25% in NP group. No significant differences were detected between the 2 groups. The incidence rates of phlebitis and grade I-II peripheral neuritis were significantly higher in NO group than in NP group (77.59% vs. 50.00%, Pvs. 15.63%, PNP group than in NO group (31.25% vs. 3.45%, PNP regimen, but the clinical benefit response rate is higher in NO group than in NP group. In short, NO regimen may be recommended as the first-line chemotherapy regimen for advanced NSCLC.

  5. 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.

  6. Dengue 4 Vaccine Development

    Science.gov (United States)

    1987-09-01

    and monkeys. b) Preparation of a production seed from uncloned Dengue 4 (H241) PDK-35 vaccine isolated from viremic serum of a volunteer vaccinee , and... synthetic peptide vaccines , work on development of live attenuated virus vaccines continues. Experimental attenuated live virus vaccines -I- for protection...CopU~1C FftE 0~AD( ) DENGUE 4 VACCINE DEVELOPMENT Lf 0, to ANNUAL AND FINAL REPORT0 by 0Nyven J. Marchette, Ph.D. September 1, 1987 (For the period 1

  7. 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...

  8. Combining biomedical preventions for HIV: Vaccines with pre-exposure prophylaxis, microbicides or other HIV preventions

    Science.gov (United States)

    McNicholl, Janet M.

    2016-01-01

    ABSTRACT 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. PMID:27679928

  9. Vaccines against malaria.

    Science.gov (United States)

    Hill, Adrian V S

    2011-10-12

    There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.

  10. Mamu-A*01/Kb transgenic and MHC Class I knockout mice as a tool for HIV vaccine development

    International Nuclear Information System (INIS)

    Li Jinliang; Srivastava, Tumul; Rawal, Ravindra; Manuel, Edwin; Isbell, Donna; Tsark, Walter; La Rosa, Corinna; Wang Zhongde; Li Zhongqi; Barry, Peter A.; Hagen, Katharine D.; Longmate, Jeffrey; Diamond, Don J.

    2009-01-01

    We have developed a murine model expressing the rhesus macaque (RM) Mamu-A*01 MHC allele to characterize immune responses and vaccines based on antigens of importance to human disease processes. Towards that goal, transgenic (Tg) mice expressing chimeric RM (α1 and α2 Mamu-A*01 domains) and murine (α3, transmembrane, and cytoplasmic H-2K b domains) MHC Class I molecules were derived by transgenesis of the H-2K b D b double MHC Class I knockout strain. After immunization of Mamu-A*01/K b Tg mice with rVV-SIVGag-Pol, the mice generated CD8 + T-cell IFN-γ responses to several known Mamu-A*01 restricted epitopes from the SIV Gag and Pol antigen sequence. Fusion peptides of highly recognized CTL epitopes from SIV Pol and Gag and a strong T-help epitope were shown to be immunogenic and capable of limiting an rVV-SIVGag-Pol challenge. Mamu-A*01/K b Tg mice provide a model system to study the Mamu-A*01 restricted T-cell response for various infectious diseases which are applicable to a study in RM.

  11. Şemseddin Sivȃsȋ’nin Tasavvufȋ Tecrübesinde Rizȃ-yı Bȃrȋ Düşüncesi

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    Kadir Özköse

    2015-12-01

    Full Text Available Halvetiyyenin dört ana kolundan biri olan Şemsiyyenin pȋri konumundaki Şemseddin Sivȃsȋ’nin eserlerinden hareketle hazırladığımız bu makale Şemseddin Sivȃsȋ’nin sȗfȋ tecrübesini okumaya dönük bir çalışmadır. Mensur ve manzum eserlerinin herbirinde Şemseddin Sivȃsȋ ana tema olarak Allah’ın rızasını merkeze almıştır. İlahi rızanın her zaman gündemde olmasını, kulluğun ilahi rıza ekseninde gerçekleşmesini istemiştir. Lutfun da hoş kahrın da hoş anlayışına bağlı olan Şemseddin Sivȃsȋ ilahi takdire boyun eğmiş, ne varlığa sevinmeyi ne de yokluktan yerinmeyi öngörmüştür. Rıza halinin kemalini o, mücahede eğitimne, sabır ve sebat gayretine, tevazu duygusuna, ihlas hassasiyetine ve zikir diriliğine bağlamıştır. Makalemizde Şemseddin Sivȃsȋ’nin rızanın ehemmiyetine ve rıza makamına ulaşmayı sağlayan teel ölçütlere dikkat çekmeye çalıştık.

  12. 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

  13. Viral RNA levels and env variants in semen and tissues of mature male rhesus macaques infected with SIV by penile inoculation.

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    Francis Fieni

    Full Text Available HIV is shed in semen but the anatomic site of virus entry into the genital secretions is unknown. We determined viral RNA (vRNA levels and the envelope gene sequence in the SIVmac 251 viral populations in the genital tract and semen of 5 adult male rhesus monkeys (Macaca mulatta that were infected after experimental penile SIV infection. Paired blood and semen samples were collected from 1-9 weeks after infection and the monkeys were necropsied eleven weeks after infection. The axillary lymph nodes, testes, epididymis, prostate, and seminal vesicles were collected and vRNA levels and single-genome analysis of the SIVmac251 env variants was performed. At the time of semen collection, blood vRNA levels were between 3.09 and 7.85 log10 vRNA copies/ml plasma. SIV RNA was found in the axillary lymph nodes of all five monkeys and in 3 of 5 monkeys, all tissues examined were vRNA positive. In these 3 monkeys, vRNA levels (log10 SIVgag copies/ug of total tissue RNA in the axillary lymph node (6.48 ± 0.50 were significantly higher than in the genital tract tissues: testis (3.67 ± 2.16; p<0.05, epididymis (3.08 ± 1.19; p<0.0001, prostate (3.36 ± 1.30; p<0.01, and seminal vesicle (2.67 ± 1.50; p<0.0001. Comparison of the SIVmac251 env viral populations in blood plasma, systemic lymph node, and genital tract tissues was performed in two of the macaques. Visual inspection of the Neighbor-Joining phylograms revealed that in both animals, all the sequences were generally distributed evenly among all tissue compartments. Importantly, viral populations in the genital tissues were not distinct from those in the systemic tissues. Our findings demonstrate striking similarity in the viral populations in the blood and male genital tract tissues within 3 months of penile SIV transmission.

  14. Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset

    Science.gov (United States)

    Ploquin, Mickaël J.; Casrouge, Armanda; Huot, Nicolas; Passaes, Caroline; Lécuroux, Camille; Essat, Asma; Boufassa, Faroudy; Jacquelin, Béatrice; Jochems, Simon P.; Petitjean, Gaël; Angin, Mathieu; Gärtner, Kathleen; Garcia-Tellez, Thalía; Booiman, Thijs; Boeser-Nunnink, Brigitte D.; Roques, Pierre; Saez-Cirion, Asier; Vaslin, Bruno; Dereudre-Bosquet, Nathalie; Barré-Sinoussi, Françoise; Ghislain, Mathilde; Rouzioux, Christine; Lambotte, Olivier; Albert, Matthew L.; Goujard, Cécile; Kootstra, Neeltje; Meyer, Laurence; Müller-Trutwin, Michaela C.

    2016-01-01

    Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI) were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort), as well as during controlled and uncontrolled viremia (ANRS cohorts). We also addressed IP-10 expression levels with regards to lymphoid tissues (LT) and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker) gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10. PMID:27509048

  15. Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset.

    Directory of Open Access Journals (Sweden)

    Mickaël J Ploquin

    2016-08-01

    Full Text Available Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort, as well as during controlled and uncontrolled viremia (ANRS cohorts. We also addressed IP-10 expression levels with regards to lymphoid tissues (LT and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10.

  16. HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells

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    John Zaunders

    2017-04-01

    Full Text Available BackgroundT follicular helper (Tfh cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4+ T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells.MethodologyTfh and other CD4+ T cell subsets from macaque lymph nodes and spleens, splenic Tfh from HIV+ subjects, and tonsillar Tfh from HIV-uninfected subjects were isolated by cell sorting prior to cell surface and molecular characterization. HIV proviral gp120 sequences were submitted to genotypic and phenotypic tropism assays. Entry of CCR5- and CXCR4-using viruses into Tfh from uninfected tonsillar tissue was measured using a fusion assay.ResultsPhylogenetic analysis, genotypic, and phenotypic analysis showed that splenic Tfh cells from chronic HIV+ subjects were predominantly infected with CCR5-using viruses. In macaques, purified CCR5+PD-1intermediate(int+ memory CD4+ T cells were shown to include pre-Tfh cells capable of differentiating in vitro to Tfh by upregulation of PD-1 and Bcl6, confirmed by qRT-PCR and single-cell multiplex PCR. Infected PD-1int cells survive, carry SIV provirus, and differentiate into PD-1hi Tfh after T cell receptor stimulation, suggesting a pathway for SIV infection of Tfh. In addition, a small subset of macaque and human PD-1hi Tfh can express low levels of CCR5, which makes them susceptible to infection. Fusion assays demonstrated CCR5-using HIV-1 entry into CCR5+ Tfh and pre-Tfh cells from human tonsils.ConclusionThe major route of infection of Tfh in macaques and humans appears to be via a CCR5-expressing pre-Tfh population

  17. HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells.

    Science.gov (United States)

    Xu, Yin; Phetsouphanh, Chansavath; Suzuki, Kazuo; Aggrawal, Anu; Graff-Dubois, Stephanie; Roche, Michael; Bailey, Michelle; Alcantara, Sheilajen; Cashin, Kieran; Sivasubramaniam, Rahuram; Koelsch, Kersten K; Autran, Brigitte; Harvey, Richard; Gorry, Paul R; Moris, Arnaud; Cooper, David A; Turville, Stuart; Kent, Stephen J; Kelleher, Anthony D; Zaunders, John

    2017-01-01

    T follicular helper (Tfh) cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4 + T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells. Tfh and other CD4 + T cell subsets from macaque lymph nodes and spleens, splenic Tfh from HIV + subjects, and tonsillar Tfh from HIV-uninfected subjects were isolated by cell sorting prior to cell surface and molecular characterization. HIV proviral gp120 sequences were submitted to genotypic and phenotypic tropism assays. Entry of CCR5- and CXCR4-using viruses into Tfh from uninfected tonsillar tissue was measured using a fusion assay. Phylogenetic analysis, genotypic, and phenotypic analysis showed that splenic Tfh cells from chronic HIV + subjects were predominantly infected with CCR5-using viruses. In macaques, purified CCR5 + PD-1 intermediate(int)+ memory CD4 + T cells were shown to include pre-Tfh cells capable of differentiating in vitro to Tfh by upregulation of PD-1 and Bcl6, confirmed by qRT-PCR and single-cell multiplex PCR. Infected PD-1 int cells survive, carry SIV provirus, and differentiate into PD-1 hi Tfh after T cell receptor stimulation, suggesting a pathway for SIV infection of Tfh. In addition, a small subset of macaque and human PD-1 hi Tfh can express low levels of CCR5, which makes them susceptible to infection. Fusion assays demonstrated CCR5-using HIV-1 entry into CCR5 + Tfh and pre-Tfh cells from human tonsils. The major route of infection of Tfh in macaques and humans appears to be via a CCR5-expressing pre-Tfh population. As the generation of Tfh are important

  18. Noncompliance with Medical Regimen in Haemodialysis Treatment: A Case Study

    Directory of Open Access Journals (Sweden)

    Paraskevi Theofilou

    2011-01-01

    Full Text Available Patients undergoing haemodialysis treatment have a high burden of disease (particularly cardiovascular comorbidities affecting their quality of life and dramatically shortening life expectancy. Effective chronic kidney disease (CKD control requires regular preventive medication and a response to that medication. Poor receptiveness to CKD medication can be related to individual variability in the dose needed to achieve a response, as well as to low-adherent behaviour in relation to the CKD medication regimen. Some patients, though not many, according to studies' findings, abuse the medical regimen as a result of suicidal tendencies. The present case gave us the opportunity to consider the causes and clinical findings and review the specific psychological interventions for patients with CKD.

  19. Costs of diarrheal disease and the cost-effectiveness of a rotavirus vaccination program in kyrgyzstan.

    Science.gov (United States)

    Flem, Elmira T; Latipov, Renat; Nurmatov, Zuridin S; Xue, Yiting; Kasymbekova, Kaliya T; Rheingans, Richard D

    2009-11-01

    We examined the cost-effectiveness of a rotavirus immunization program in Kyrgyzstan, a country eligible for vaccine funding from the GAVI Alliance. We estimated the burden of rotavirus disease and its economic consequences by using national and international data. A cost-effectiveness analysis was conducted from government and societal perspectives, along with a range of 1-way sensitivity analyses. Rotavirus-related hospitalizations and outpatient visits cost US$580,864 annually, of which $421,658 (73%) is direct medical costs and $159,206 (27%) is nonmedical and indirect costs. With 95% coverage, vaccination could prevent 75% of rotavirus-related hospitalizations and deaths and 56% of outpatient visits and could avert $386,193 (66%) in total costs annually. The medical break-even price at which averted direct medical costs equal vaccination costs is $0.65/dose; the societal break-even price is $1.14/dose for a 2-dose regimen. At the current GAVI Alliance-subsidized vaccine price of $0.60/course, rotavirus vaccination is cost-saving for the government. Vaccination is cost-effective at a vaccine price $9.41/dose, according to the cost-effectiveness standard set by the 2002 World Health Report. Addition of rotavirus vaccines to childhood immunization in Kyrgyzstan could substantially reduce disease burden and associated costs. Vaccination would be cost-effective from the national perspective at a vaccine price $9.41 per dose.

  20. Dynamic changes in cellular infiltrates with repeated cutaneous vaccination: a histologic and immunophenotypic analysis

    Directory of Open Access Journals (Sweden)

    Schaefer Jochen T

    2010-08-01

    Full Text Available Abstract Background Melanoma vaccines have not been optimized. Adjuvants are added to activate dendritic cells (DCs and to induce a favourable immunologic milieu, however, little is known about their cellular and molecular effects in human skin. We hypothesized that a vaccine in incomplete Freund's adjuvant (IFA would increase dermal Th1 and Tc1-lymphocytes and mature DCs, but that repeated vaccination may increase regulatory cells. Methods During and after 6 weekly immunizations with a multipeptide vaccine, immunization sites were biopsied at weeks 0, 1, 3, 7, or 12. In 36 participants, we enumerated DCs and lymphocyte subsets by immunohistochemistry and characterized their location within skin compartments. Results Mature DCs aggregated with lymphocytes around superficial vessels, however, immature DCs were randomly distributed. Over time, there was no change in mature DCs. Increases in T and B-cells were noted. Th2 cells outnumbered Th1 lymphocytes after 1 vaccine 6.6:1. Eosinophils and FoxP3+ cells accumulated, especially after 3 vaccinations, the former cell population most abundantly in deeper layers. Conclusions A multipeptide/IFA vaccine may induce a Th2-dominant microenvironment, which is reversed with repeat vaccination. However, repeat vaccination may increase FoxP3+T-cells and eosinophils. These data suggest multiple opportunities to optimize vaccine regimens and potential endpoints for monitoring the effects of new adjuvants. Trail Registration ClinicalTrials.gov Identifier: NCT00705640

  1. Pilot study of a pediatric metronomic 4-drug regimen.

    Science.gov (United States)

    André, Nicolas; Abed, Sylvie; Orbach, Daniel; Alla, Corinne Armari; Padovani, Laetitia; Pasquier, Eddy; Gentet, Jean Claude; Verschuur, Arnauld

    2011-12-01

    Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. MC is gaining interest as an alternative strategy to fight resistant cancer. to assess the safety of 4 drug MC regimen in paediatric patients with refractory or relapsing various tumour types. From November 2008 to December 2010, in three academic paediatric oncology centers, 16 children (median age 12 years old; range 5.5-20) were included in this pilot study. This treatment was proposed to children with refractory disease for whom no further effective treatments were available. Most frequent diagnosis were medulloblastoma/cerebral PNET (5) osteosarcoma (5), and one case each of nephroblastoma, high grade glioma, Hodgkin lymphoma, rhabdomyosarcoma, neuroblastoma and kidney rhabdoid tumour. The MC regimen consisted in cycles of 56 days (8 weeks) with weekly vinblastine 3 mg/m2 (week 1-7), daily cyclophosphamide 30 mg/m2 (days 1-21), and twice weekly methotrexate 10 mg/m² (days 21-42), and daily celecoxib 100 mg to 400 mg twice daily (days 1-56) followed by a 2-weeks chemotherapy break. Adverse events were determined through laboratory analysis and investigator observations. One objective response was observed in a patient with Hodgkin lymphoma, and 4 patients experienced disease stabilization and continued their treatment for 3 cycles (24 weeks) or more. At last follow-up, 7 patients (43%) are alive including 1 still undergoing treatment. During the overall 36 cycles of treatments received by patients, 4 grade IV toxicities and 24 grade III toxicities were observed in 11 cycles in only 10 different patients. The metronomic regimen we report here was well tolerated and associated with disease stabilization. This regimen is currently being evaluated in a national multicenter phase II study.

  2. A comparative study of various therapeutic regimens in urticaria

    Directory of Open Access Journals (Sweden)

    Mukhopadhyay Amiyakumar

    1995-01-01

    Full Text Available 127 patients of urticaria were treated with chlorpheniramine maleate alone and in combination with cyproheptadine hydrochloride, ranitidine and doxepin and levamisole. Chlorpheniramine and doxepin combination showed a satisfactory result in 88.46% of patients. Overall study showed that a combination regimen is better than the antihistaminics alone. Drowsiness was the commonest side effect. Levamisole and chlorpheniramine maleate combination was found to be more effective than the antihimstamine alone.

  3. Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age.

    Science.gov (United States)

    Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

    2014-01-01

    Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76-98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period.

  4. A prospective study on the efficacy of two-dose influenza vaccinations in cancer patients receiving chemotherapy.

    Science.gov (United States)

    Sanada, Yukinari; Yakushijin, Kimikazu; Nomura, Tetsuhiko; Chayahara, Naoko; Toyoda, Masanori; Minami, Yosuke; Kiyota, Naomi; Mukohara, Toru; Kawamoto, Shinichiro; Ito, Mitsuhiro; Matsuoka, Hiroshi; Minami, Hironobu

    2016-05-01

    Cancer patients receiving chemotherapy are at risk of acquiring influenza infections. Two-dose vaccination is a proposed strategy for increasing vaccination efficacy; however, this has yet to be confirmed in this population. The purpose of this study was to clarify the efficacy and safety of this strategy. We conducted a multicentre prospective study on a two-dose vaccination regimen in cancer patients receiving chemotherapy. Second vaccinations were performed in patients who did not respond to all three viral strains after the first vaccination. Serum haemagglutination inhibition titres were measured to determine the patients' immunological response, 2 weeks prior to the first vaccination, 3-5 weeks after each vaccination, and at the end of the influenza season. We enrolled 109 patients, including 70 with solid tumours, 36 with haematological malignancies, and 3 with both cancer types. Among the total patients, the proportion of patients with protective titres against the three viral strains increased significantly from 3 to 27% (P vaccination. Among the 79 patients who received a second vaccination, the proportion of those with protective titres against the individual strains increased by 10% (H1N1), 8% (H3N2), and 3% (B) compared with after the first vaccination. Serious adverse events were not observed. We recommend influenza vaccinations for cancer patients, including those receiving chemotherapy. Also, the additional benefit of the second vaccination may be limited. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. A systems approach to designing next generation vaccines: combining α-galactose modified antigens with nanoparticle platforms

    Science.gov (United States)

    Phanse, Yashdeep; Carrillo-Conde, Brenda R.; Ramer-Tait, Amanda E.; Broderick, Scott; Kong, Chang Sun; Rajan, Krishna; Flick, Ramon; Mandell, Robert B.; Narasimhan, Balaji; Wannemuehler, Michael J.

    2014-01-01

    Innovative vaccine platforms are needed to develop effective countermeasures against emerging and re-emerging diseases. These platforms should direct antigen internalization by antigen presenting cells and promote immunogenic responses. This work describes an innovative systems approach combining two novel platforms, αGalactose (αGal)-modification of antigens and amphiphilic polyanhydride nanoparticles as vaccine delivery vehicles, to rationally design vaccine formulations. Regimens comprising soluble αGal-modified antigen and nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity antibody response with broader epitope recognition of antigenic peptides than other regimen. Proliferation of antigen-specific CD4+ T cells was also enhanced compared to a traditional adjuvant. Combining the technology platforms and augmenting immune response studies with peptide arrays and informatics analysis provides a new paradigm for rational, systems-based design of next generation vaccine platforms against emerging and re-emerging pathogens.

  6. Predictive tools for designing new insulins and treatment regimens

    DEFF Research Database (Denmark)

    Klim, Søren

    The thesis deals with the development of "Predictive tools for designing new insulins and treatments regimens" and consists of two parts: A model based approach for bridging properties of new insulin analogues from glucose clamp experiments to meal tolerance tests (MTT) and a second part that des......The thesis deals with the development of "Predictive tools for designing new insulins and treatments regimens" and consists of two parts: A model based approach for bridging properties of new insulin analogues from glucose clamp experiments to meal tolerance tests (MTT) and a second part...... glucose profiles from a MTT with treatments based on the new insulin analogue that previously only has been tested in clamps. The bridge between insulin analogue properties determined in clamp experiments to meal tolerance test outcomes in Phase II trials is not simple and is complicated by shifts...... in experimental setup, time horizon and treatment regimen. A bridging strategy was introduced where an integrated model simulating MTTs was extended with models developed on clamp data that described PK and PD for the new insulin analogue. The bridging strategy was tested by building an integrated model based...

  7. The Hemotoxicity of Chemotherapeutic Regimens in Sudanese Children with Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Fathelrahman Mahdi Hassan

    2013-01-01

    Full Text Available Background: There has been a rapid increase in cancer among Sudanese citizens from 1999 until this year. At least 80% of all patients who undergo chemotherapy will develop anemia as a complication. This inpatient analytical comparative study aims to examine the possible association between hemotoxicity and various chemotherapy regimens in Sudanese children diagnosed with retinoblastoma.Methods: This study enrolled 30 patients diagnosed with childhood retinoblastoma who were admitted from June 2006 to September 2008 to the Radiation and Isotope Center Khartoum. We collected 90 blood samples to examine for a possible association between anemia and the chemotherapeutic regimen. All patients (n=30 were included in each arm of the chemotherapy regimen.Results: Prior to the onset of chemotherapy, 50% of patients had normal hemoglobin levels, 43.3% had mild anemia, and 6.7% had moderate anemia. Post-cycle I treatment, there were only 6.7% who had normal hemoglobin levels. Mild anemia was observed in 60%, followed by 30% for moderate anemia and 3.3% of patients had severe anemia. Post-cycle II there were no patients with normal hemoglobin levels, however 26.7% had mild anemia and the majority of patients (approximately 73.3% had moderate anemia.Conclusion: A correlation existed between hemoglobin values after completion of therapy to the overall treatment. We observed a decline of 1 to 2 g/dl in hemoglobin levels.

  8. Vaccine-Preventable Disease Photos

    Science.gov (United States)

    ... BASICS Evaluating Online Health Information FAQs How Vaccines Work Importance of Vaccines Paying for Vaccines State Immunization Programs ... Immunization Action Coalition (IAC), a non-profit organization, works to ... facilitates communication about the safety, efficacy, and use of vaccines ...

  9. Vaccinations for Adults with Diabetes

    Science.gov (United States)

    Vaccinations for Adults with Diabetes The table below shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...

  10. 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... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a doctor...

  11. 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

  12. Intranasal administration of a proteosome-influenza vaccine is well-tolerated and induces serum and nasal secretion influenza antibodies in healthy human subjects.

    Science.gov (United States)

    Treanor, John; Nolan, Carrie; O'Brien, Diane; Burt, David; Lowell, George; Linden, Janine; Fries, Louis

    2006-01-16

    Two randomized, blinded, active comparator-controlled trials of a prototype monovalent A/Beijing/262/95 (H1N1) - proteosome vaccine delivered by intranasal spray were performed in healthy adults. Overall, the intranasal proteosome-adjuvanted vaccine was well-tolerated with only mild stuffy nose and rhinorrhea seen more frequently in recipients of vaccine than in recipients of intranasal saline, and there were no serious adverse events. The intranasal proteosome-adjuvanted vaccine induced serum hemagglutination inhibiting (HAI) and nasal secretory IgA (sIgA) responses specific for the influenza antigen. Serum HAI responses were most influenced by the dosage level, whereas mucosal sIgA responses, although demonstrable with both single-dose and two-dose vaccine regimens, appeared to be greater in response to two-dose regimens (regardless of dose level). Further evaluation of mucosal influenza immunization using the proteosome adjuvant/delivery system is clearly warranted.

  13. Heterologous Prime-Boost Immunisation Regimens Against Infectious Diseases

    Science.gov (United States)

    2006-08-01

    virulence challenge. Vet Res 2003, 34(1), 119-125. 95 Degano, P., Schneider, J., Hannan, C.M., Gilbert, S.C. & Hill, A.V. Gene gun intradermal DNA...phosphate guanosine oligodeoxynucleotide (CpG) as an adjuvant with protein as a prime followed by adenovirus boost [62]; a rabies virus (RV) vaccine...intratracheal virulent M. Bovis challenge even though the elicited T-cell responses were higher than those seen in the DNA alone vaccinated group of animals

  14. The potential economic value of a Trypanosoma cruzi (Chagas disease) vaccine in Latin America.

    Science.gov (United States)

    Lee, Bruce Y; Bacon, Kristina M; Connor, Diana L; Willig, Alyssa M; Bailey, Rachel R

    2010-12-14

    Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), is the leading etiology of non-ischemic heart disease worldwide, with Latin America bearing the majority of the burden. This substantial burden and the limitations of current interventions have motivated efforts to develop a vaccine against T. cruzi. We constructed a decision analytic Markov computer simulation model to assess the potential economic value of a T. cruzi vaccine in Latin America from the societal perspective. Each simulation run calculated the incremental cost-effectiveness ratio (ICER), or the cost per disability-adjusted life year (DALY) avoided, of vaccination. Sensitivity analyses evaluated the impact of varying key model parameters such as vaccine cost (range: $0.50-$200), vaccine efficacy (range: 25%-75%), the cost of acute-phase drug treatment (range: $10-$150 to account for variations in acute-phase treatment regimens), and risk of infection (range: 1%-20%). Additional analyses determined the incremental cost of vaccinating an individual and the cost per averted congestive heart failure case. Vaccination was considered highly cost-effective when the ICER was ≤1 times the GDP/capita, still cost-effective when the ICER was between 1 and 3 times the GDP/capita, and not cost-effective when the ICER was >3 times the GDP/capita. Our results showed vaccination to be very cost-effective and often economically dominant (i.e., saving costs as well providing health benefits) for a wide range of scenarios, e.g., even when risk of infection was as low as 1% and vaccine efficacy was as low as 25%. Vaccinating an individual could likely provide net cost savings that rise substantially as risk of infection or vaccine efficacy increase. Results indicate that a T. cruzi vaccine could provide substantial economic benefit, depending on the cost of the vaccine, and support continued efforts to develop a human vaccine.

  15. 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.

  16. 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.

  17. A prospective, Internet-based study of the effectiveness and safety of influenza vaccination in the 2001-2002 influenza season.

    Science.gov (United States)

    Kawai, Naoki; Ikematsu, Hideyuki; Iwaki, Norio; Satoh, Ietaka; Kawashima, Takashi; Tsuchimoto, Taizo; Kashiwagi, Seizaburo

    2003-11-07

    The effectiveness of the influenza vaccine used in the 2001-2002 influenza season in Japan was investigated in a large-scale, geographically widely distributed, Internet-based study. Data were collected from 8841 of 9902 subjects registered by 38 clinics prior to the start of influenza season. Subjects were categorized into three groups by vaccination regimen: unvaccinated, vaccinated once, and vaccinated twice. Efficacy was also analyzed for three age groups: 0-15, 16-64, and 65-104 years. Influenza-like illness (ILI) was diagnosed according to Ministry of Health (MWH, Labor and Welfare in Japan) criteria. Laboratory-confirmed influenza cases were analyzed separately. The respective vaccine efficacy in the 0-15 years group for the one- and two-dose regimens was 67.6 and 84.5% for ILI and 54.0 and 79.8% for laboratory-confirmed influenza. Influenza vaccination was also shown to be effective in subjects 16-64 years. Vaccine effectiveness was not able to be determined for the over 65 years group, probably due to an insufficient number of infected patients. These results suggest that influenza vaccination is effective for children and adults and that a two-dose regimen is superior to a single dose in children 0-15 years.

  18. Rabies post-exposure prophylaxis for a child with severe allergic reaction to rabies vaccine.

    Science.gov (United States)

    Fang, Yuan; Liu, Man-Qing; Chen, Li; Zhu, Zheng-Gang; Zhu, Ze-Rong; Hu, Quan

    2016-07-02

    Most adverse events (AEs) during the immunization of rabies vaccine were slight, there was little information about the allergic reaction induced by rabies vaccines and had to stop or change the immunization program. Here, we reported a case that a 4-year-old boy had category II exposure to rabies and showed severe allergic reaction after being immunized with lyophilized purified vero cell rabies vaccine (PVRV). After the anti-allergy therapy with hormone, allergy testing indicated medium allergy to egg and milk, and implied the allergic reaction most likely associated with animal-sourced gelatin in lyophilized PVRV. Therefore, a new immunization program with liquid PVRV without stabilizers under the Zegrab regimen (2-1-1) was enrolled at day 7 post-exposure. Although lower than the levels of normal rabies vaccines co-existing in the market, but also implied the necessary for doctors to fully understand the allergies history of patients prior to immunize rabies vaccine.

  19. Impact of Anesthetic Regimen on Remote Ischemic Preconditioning in the Rat Heart In Vivo

    NARCIS (Netherlands)

    Behmenburg, Friederike; van Caster, Patrick; Bunte, Sebastian; Brandenburger, Timo; Heinen, André; Hollmann, Markus W.; Huhn, Ragnar

    2017-01-01

    Remote ischemic preconditioning (RIPC) seems to be a promising cardioprotective strategy with contradictive clinical data suggesting the anesthetic regimen influencing the favorable impact of RIPC. This study aimed to investigate whether cardio protection by RIPC is abolished by anesthetic regimens.

  20. Chemotherapy for pulmonary large cell neuroendocrine carcinomas : Does the regimen matter?

    NARCIS (Netherlands)

    Derks, Jules L.; van Suylen, Robert Jan; Thunnissen, Erik; den Bakker, Michael A.; Groen, Harry J.; Smit, Egbert F.; Damhuis, Ronald A.; van den Broek, Esther C.; Speel, Ernst-Jan M.; Dingemans, Anne-Marie C.

    Pulmonary large cell neuroendocrine carcinoma (LCNEC) is rare. Chemotherapy for metastatic LCNEC ranges from small cell lung carcinoma (SCLC) regimens to nonsmall cell lung carcinoma (NSCLC) chemotherapy regimens. We analysed outcomes of chemotherapy treatments for LCNEC. The Netherlands Cancer

  1. Effect of a short-term HAART on SIV load in macaque tissues is dependent on time of initiation and antiviral diffusion

    Directory of Open Access Journals (Sweden)

    Durand-Gasselin Lucie

    2010-09-01

    Full Text Available Abstract Background HIV reservoirs are rapidly established after infection, and the effect of HAART initiated very early during acute infection on HIV reservoirs remains poorly documented, particularly in tissue known to actively replicate the virus. In this context, we used the model of experimental infection of macaques with pathogenic SIV to assess in different tissues: (i the effect of a short term HAART initiated at different stages during acute infection on viral dissemination and replication, and (ii the local concentration of antiviral drugs. Results Here, we show that early treatment with AZT/3TC/IDV initiated either within 4 hours after intravenous infection of macaques with SIVmac251 (as a post exposure prophylaxis or before viremia peak (7 days post-infection [pi], had a strong impact on SIV production and dissemination in all tissues but did not prevent infection. When treatment was initiated after the viremia peak (14 days pi or during early chronic infection (150 days pi, significant viral replication persists in the peripheral lymph nodes and the spleen of treated macaques despite a strong effect of treatment on viremia and gut associated lymphoid tissues. In these animals, the level of virus persistence in tissues was inversely correlated with local concentrations of 3TC: high concentrations of 3TC were measured in the gut whereas low concentrations were observed in the secondary lymphoid tissues. IDV, like 3TC, showed much higher concentration in the colon than in the spleen. AZT concentration was below the quantification threshold in all tissues studied. Conclusions Our results suggest that limited antiviral drug diffusion in secondary lymphoid tissues may allow persistent viral replication in these tissues and could represent an obstacle to HIV prevention and eradication.

  2. 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...

  3. Immune Interference After Sequential Alphavirus Vaccine Vaccinations

    Science.gov (United States)

    2009-01-01

    containing 50gmL−1 each of neomycin and streptomycin and supplemented with 0.5% human serum albumin , U.S.P. The lyophilized vaccine is the filtered...vaccine was prepared from specific pathogen-free eggs infected with the attenuated CM4884 strain of WEE virus. The supernatant was harvested and filtered...supernatant harvested from primary chicken embryo cell cultures. The vaccine was prepared from spe- cific pathogen-free eggs infected with the

  4. Virological patterns of HCV patients with failure to interferon-free regimens.

    Science.gov (United States)

    Starace, Mario; Minichini, Carmine; De Pascalis, Stefania; Macera, Margherita; Occhiello, Laura; Messina, Vincenzo; Sangiovanni, Vincenzo; Adinolfi, Luigi E; Claar, Ernesto; Precone, Davide; Stornaiuolo, Gianfranca; Stanzione, Maria; Ascione, Tiziana; Caroprese, Mara; Zampino, Rosa; Parrilli, Gianpaolo; Gentile, Ivan; Brancaccio, Giuseppina; Iovinella, Vincenzo; Martini, Salvatore; Masarone, Mario; Fontanella, Luca; Masiello, Addolorata; Sagnelli, Evangelista; Punzi, Rodolfo; Salomone Megna, Angelo; Santoro, Renato; Gaeta, Giovanni B; Coppola, Nicola

    2018-05-01

    The study characterized the virological patterns and the resistance-associated substitutions (RASs) in patients with failure to IFN-free regimens enrolled in the real-life setting. All 87 consecutive HCV patients with failed IFN-free regimens, observed at the laboratory of the University of Campania, were enrolled. All patients had been treated with DAA regimens according to the HCV genotype, international guidelines, and local availability. Sanger sequencing of NS3, NS5A, and NS5B regions was performed at failure by home-made protocols. Of the 87 patients enrolled, 13 (14.9%) showed a misclassified HCV genotype, probably causing DAA failure, 16 had been treated with a sub-optimal DAA regimen, 19 with a simeprevir-based regimen and 39 with an optimal DAA regimen. A major RAS was identified more frequently in the simeprevir regimen group (68.4%) and in the optimal regimen group (74.4%) than in the sub-optimal regimen group (56.3%). The prevalence of RASs in NS3 was similar in the three groups (30.8-57.9%), that in NS5A higher in the optimal regimen group (71.8%) than in the sub-optimal regimen group (12.5%, P < 0.0001) and in the simeprevir regimen group (31.6%, P < 0.0005), and that in NS5B low in all groups (0-25%). RASs in two or more HCV regions were more frequently identified in the optimal regimen group (46.6%) than in the simeprevir-based regimen group (31.6%) and sub-optimal regimen group (18.7%). In our real-life population the prevalence of RASs was high, especially in NS3 and NS5A and in those treated with suitable DAA regimens. © 2018 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    Attenuvax® Measles Vaccine ... R-Vax® II (as a combination product containing Measles Vaccine, Rubella Vaccine) ... M-R® II (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine)

  6. Comparison of efficacy and pharmacoeconomics of two helicobacter pylori eradication regimens in peptic ulcer disease

    Directory of Open Access Journals (Sweden)

    Syeda Zaineb Kubra Hussaini

    2018-01-01

    Conclusion: Our study showed that Regimen II (RAM was more cost-effective than Regimen I (PAC, but PAC achieved faster H. pylori eradication than RAM. We assume that this study provides local clinical data as to which regimen may be useful in a particular patient. National Level Clinical Trials are required to further ascertain this conclusion.

  7. Influenza H5 hemagglutinin DNA primes the antibody response elicited by the live attenuated influenza A/Vietnam/1203/2004 vaccine in ferrets.

    Directory of Open Access Journals (Sweden)

    Amorsolo L Suguitan

    Full Text Available Priming immunization plays a key role in protecting individuals or populations to influenza viruses that are novel to humans. To identify the most promising vaccine priming strategy, we have evaluated different prime-boost regimens using inactivated, DNA and live attenuated vaccines in ferrets. Live attenuated influenza A/Vietnam/1203/2004 (H5N1 candidate vaccine (LAIV, VN04 ca primed ferrets efficiently while inactivated H5N1 vaccine could not prime the immune response in seronegative ferrets unless an adjuvant was used. However, the H5 HA DNA vaccine alone was as successful as an adjuvanted inactivated VN04 vaccine in priming the immune response to VN04 ca virus. The serum antibody titers of ferrets primed with H5 HA DNA followed by intranasal vaccination of VN04 ca virus were comparable to that induced by two doses of VN04 ca virus. Both LAIV-LAIV and DNA-LAIV vaccine regimens could induce antibody responses that cross-neutralized antigenically distinct H5N1 virus isolates including A/HongKong/213/2003 (HK03 and prevented nasal infection of HK03 vaccine virus. Thus, H5 HA DNA vaccination may offer an alternative option for pandemic preparedness.

  8. Rabies intradermal post-exposure vaccination of humans using reconstituted and stored vaccine.

    Science.gov (United States)

    Kamoltham, Thavachai; Khawplod, Pakamatz; Wilde, Henry

    2002-09-10

    Thailand's northern Petchabun province is endemic for canine rabies. There were 27 reported human rabies deaths between 1989 and 1998. A rabies control plan was formulated in 1997 between medical and veterinary public health officials. It started an intense education program and an ongoing dog vaccination campaign. Economic constraints and the high cost of biological were the main reasons for inadequate human post-exposure management (PET). It was therefore decided to use the economical Thai Red Cross Intradermal Vaccine Regimen (TRC-ID) throughout the province. The original TRC-ID method is only suitable for clinics that see more than one PET patient daily. TRC-ID was therefore modified by storing the reconstituted vaccine in a refrigerator for the same patient's next two visits. Data on a total of 8157 PET patients were collected. An additional modification of TRC-ID also eliminated the 90 day booster. There were no treatment failures and no human rabies deaths in 1999, 2000 and 2001. The modified TRC-ID method induces adequate levels of neutralizing antibodies, protects humans bitten by rabid dogs and results in significant savings in vaccine and travel costs.

  9. 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 ...

  10. Vaccine Policy Issues

    National Research Council Canada - National Science Library

    Thaul, Susan

    2005-01-01

    .... Whether a vaccine's target is naturally occurring or present because of hostile intent, the issues policy makers must deal with include vaccine development, production, availability, safety, effectiveness, and access...

  11. 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.

  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. 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.

  14. 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.

  15. Vaccine Policy Issues

    Science.gov (United States)

    2005-05-19

    evidence “favors rejection” of the idea that either the measles- mumps-rubella vaccine or thimerosal-containing vaccines cause autism (IOM...that the vaccines or preservatives or packaging might cause autism and other neurodevelopmental disorders. One focus has been on thimerosal, a mercury...with the vaccinia virus that causes cowpox to provoke an immune response to protect against the smallpox virus. CRS-2 3A smallpox vaccine is available

  16. Vaccine Controversy Medical Oversight

    OpenAIRE

    Casady, Megan

    2010-01-01

    The anti-vaccination movement has gained significant influence because of its extremely diverse underlying support. From distrust of governmental policies regarding vaccination to scientific data that seemingly proves the dangers of vaccination, the discourses are able to reach and impact a large number of the public. My research this semester focused on the expansion of recommendations made by the Centers for Disease Control and Prevention (CDC) concerning the seasonal influenza vaccine, the...

  17. The pertussis vaccine controversy.

    OpenAIRE

    Hinman, A R

    1984-01-01

    Over the past few years, there has been continuing controversy about whether the benefits of routine vaccination for pertussis outweight the potential risks. Some of the epidemiologic and technical issues include ascertainment and reporting of cases, case definition and laboratory confirmation, identification and purification of antigens, vaccine potency measurement, vaccine efficacy, and vaccine safety. Other factors include legal and economic issues, ethical concerns, emotional overlays, an...

  18. Vaccine herd effect

    OpenAIRE

    Kim, Tae Hyong; Johnstone, Jennie; Loeb, Mark

    2011-01-01

    Vaccination ideally protects susceptible populations at high risk for complications of the infection. However, vaccines for these subgroups do not always provide sufficient effectiveness. The herd effect or herd immunity is an attractive way to extend vaccine benefits beyond the directly targeted population. It refers to the indirect protection of unvaccinated persons, whereby an increase in the prevalence of immunity by the vaccine prevents circulation of infectious agents in susceptible pop...

  19. Anti-Vaccination Movement

    OpenAIRE

    Chapman, Jonathan

    2010-01-01

    The current anti-vaccination movements that have established themselves in the United States as well as other regions in the world are like a hydra of discourse. Right when one effective measure is created to convince people to vaccinate two more anti-vaccination movements sprout up in its place. These anti-vaccination movements are driven by cultural beliefs, ideologies, medical exemption laws, non-medical exemption laws, distrust of the government, distrust of large pharmaceutical companies...

  20. Vaccine-associated hypersensitivity.

    Science.gov (United States)

    McNeil, Michael M; DeStefano, Frank

    2018-02-01

    Vaccine-associated hypersensitivity reactions are not infrequent; however, serious acute-onset, presumably IgE-mediated or IgG and complement-mediated anaphylactic or serious delayed-onset T cell-mediated systemic reactions are considered extremely rare. Hypersensitivity can occur because of either the active vaccine component (antigen) or one of the other components. Postvaccination acute-onset hypersensitivity reactions include self-limited localized adverse events and, rarely, systemic reactions ranging from urticaria/angioedema to full-blown anaphylaxis with multisystem involvement. Risk of anaphylaxis after all vaccines is estimated to be 1.31 (95% CI, 0.90-1.84) per million vaccine doses, respectively. Serious hypersensitivity reactions after influenza vaccines are particularly important because of the large number of persons vaccinated annually. Influenza vaccines are unique in requiring annual changes in the vaccines' antigenic composition to match the predicted circulating influenza strains. Recently, novel influenza vaccine types were introduced in the United States (recombinant vaccines, some with higher antigen content and a new adjuvanted vaccine). Providers should be aware of changing recommendations on the basis of recent published evidence for persons with a history of egg allergy to receive annual influenza vaccination. Further research is needed to elucidate the pathophysiology and risk factors for reported vaccine-associated adverse events. Further research is also needed to determine whether repeated annual inactivated influenza vaccination, the number of vaccine antigens administered at the same time, and the current timing of routine infant vaccinations are optimal for overall population well-being. Published by Elsevier Inc.

  1. Safety and immunogenicity of typhoid fever and yellow fever vaccines when administered concomitantly with quadrivalent meningococcal ACWY glycoconjugate vaccine in healthy adults.

    Science.gov (United States)

    Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Hlavata, Lucie Cerna; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani K

    2015-01-01

    Compact and short pre-travel immunization schedules, which include several vaccinations in a single visit, are desirable for many travelers. However, concomitant vaccination could potentially compromise immunogenicity and/or safety of the individual vaccines and, therefore, possible vaccine interferences should be carefully assessed. This article discusses the immunogenicity and safety of travel vaccines for typhoid fever (TF) and yellow fever (YF), when administered with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine (MenACWY-CRM). Healthy adults (18-≤60 years) were randomized to one of three vaccine regimens: TF + YF + MenACWY-CRM (group I; n = 100), TF + YF (group II; n = 101), or MenACWY-CRM (group III; n = 100). Immunogenicity at baseline and 4 weeks post-vaccination (day 29) was assessed by serum bactericidal assay using human complement (hSBA), enzyme-linked immunosorbent assay (ELISA), or a neutralization test. Adverse events (AEs) and serious adverse events (SAEs) were collected throughout the study period. Non-inferiority of post-vaccination geometric mean concentrations (GMCs) and geometric mean titers (GMTs) was established for TF and YF vaccines, respectively, when given concomitantly with MenACWY-CRM vaccine versus when given alone. The percentages of subjects with seroprotective neutralizing titers against YF on day 29 were similar in groups I and II. The antibody responses to meningococcal serogroups A, C, W-135, and Y were within the same range when MenACWY-CRM was given separately or together with TF and YF vaccines. The percentage of subjects reporting AEs was the same for TF and YF vaccines with or without MenACWY-CRM vaccine. There were no reports of SAEs or AEs leading to study withdrawals. These data provide evidence that MenACWY-CRM can be administered with typhoid Vi polysaccharide vaccine and live attenuated YF vaccine without compromising antibody responses stimulated by the

  2. Parasite Carbohydrate Vaccines.

    Science.gov (United States)

    Jaurigue, Jonnel A; Seeberger, Peter H

    2017-01-01

    Vaccination is an efficient means of combating infectious disease burden globally. However, routine vaccines for the world's major human parasitic diseases do not yet exist. Vaccines based on carbohydrate antigens are a viable option for parasite vaccine development, given the proven success of carbohydrate vaccines to combat bacterial infections. We will review the key components of carbohydrate vaccines that have remained largely consistent since their inception, and the success of bacterial carbohydrate vaccines. We will then explore the latest developments for both traditional and non-traditional carbohydrate vaccine approaches for three of the world's major protozoan parasitic diseases-malaria, toxoplasmosis, and leishmaniasis. The traditional prophylactic carbohydrate vaccine strategy is being explored for malaria. However, given that parasite disease biology is complex and often arises from host immune responses to parasite antigens, carbohydrate vaccines against deleterious immune responses in host-parasite interactions are also being explored. In particular, the highly abundant glycosylphosphatidylinositol molecules specific for Plasmodium, Toxoplasma , and Leishmania spp. are considered exploitable antigens for this non-traditional vaccine approach. Discussion will revolve around the application of these protozoan carbohydrate antigens for vaccines currently in preclinical development.

  3. Polysaccharide-Based Vaccines

    Science.gov (United States)

    Santana, Violeta Fernández; Balbin, Yury Valdés; Calderón, Janoi Chang; Icart, Luis Peña; Verez-Bencomo, Vicente

    Capsular polysaccharides (CPS) and lipopolysaccharides from bacteria are employed for the production of vaccines against human diseases. Initial development of CPS as a vaccine was followed by the development and introduction of conjugate polysaccharide-protein vaccines. The principles leading to both developments are reviewed.

  4. [Improving vaccination measures].

    Science.gov (United States)

    Iannazzo, S

    2014-01-01

    Despite the benefits of routine vaccination of newborns are known and widely documented, in recent years we are observing a gradual increase in the number of parents who express doubts and concerns about the safety of vaccines and the real need to submit their children to vaccinations included in the national recommendations. This attitude is reinforced by the current epidemiological profile, in Western countries, of many vaccine preventable diseases, accompanied by a low risk perception among parents. Institutions and all the actors involved in vaccination programs have a duty to investigate the reasons for the loss of confidence in vaccination among the population in order to identify and implement appropriate and effective interventions. The improvement of vaccination should, theoretically, goes on a double track, placing side by side the provision of effective vaccines, safe and necessary, and interventions designed to increase demand for vaccination among the population, improve access to vaccination services, improve the system as a whole. But to actually improve the vaccinations' offer it is necessary also to provide interventions aimed at regaining the confidence of the population in relation to vaccination and the institutions that promote them. Particular attention should be given to the aspects of communication and risk communication.

  5. Veterinary Replicon Vaccines

    NARCIS (Netherlands)

    Hikke, Mia C.; Pijlman, Gorben P.

    2017-01-01

    Vaccination is essential in livestock farming and in companion animal ownership. Nucleic acid vaccines based on DNA or RNA provide an elegant alternative to those classical veterinary vaccines that have performed suboptimally. Recent advances in terms of rational design, safety, and efficacy have

  6. 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

  7. 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.

  8. Medical Management of Ectopic Pregnancy: A Comparison of Regimens

    Science.gov (United States)

    Bachman, Emelia Argyropoulos; Barnhart, Kurt

    2012-01-01

    Medical management has become increasingly popular in the treatment of ectopic pregnancy. Given its convenience, for many it is used as a first line treatment, but this is not always the optimal choice for the patient. It is important to understand the options for medical treatment and when it is appropriate to treat a particular patient with medical management, or when one should opt for surgical management. This review outlines the different regimens for methotrexate administration and the associated risks and benefits to medical management. PMID:22510626

  9. Galeazzi fractures: our modified classification and treatment regimen.

    Science.gov (United States)

    Fayaz, H C; Jupiter, J B

    2014-02-01

    While diaphyseal fractures of the forearm are a common orthopedic injury, Galeazzi fractures are difficult to treat. The current knowledge on pathobiomechanics and modified therapeutic decisions implicate the need to devise an updated classification and treatment regimen of Galeazzi fractures. We challenge the concept that isolated fractures of the radius should be considered as a Galeazzi fractures as long as stability of the distal radioulnar joint is not proven. Contrary to others we demonstrate that the fracture location alone is not sufficient to determine the stability of the distal radioulnar joint. © Georg Thieme Verlag KG Stuttgart · New York.

  10. A Comparative Study on the Adverse Reactions of Purified Chick Embryo Cell Vaccine (PCECV) and Purified Vero Cell Rabies Vaccine (PVRV).

    Science.gov (United States)

    Ramezankhani, Roghieh; Shirzadi, Mohammad Reza; Ramezankhani, Azra; Poor Mozafary, Jamshid

    2016-07-01

    Human rabies is preventable by prompt application of post-exposure prophylaxis (PEP). The aim of this study was to compare the adverse reactions of purified vero cell rabies vaccine (PVRV) with purified chick embryo cell vaccine (PCECV) vaccination for the PEP. In this double blind clinical trial study, 1449 people bitten by animals (279 females), were recruited from 9 different cities of Iran, and randomly assigned to receive intramuscular injections of the PVRV (n = 702) and PCECV (n = 747) vaccines in 5-dose regimen. The local and systemic adverse reactions were compared between two groups. The mean age was 26.8 years (SD, ± 13.1 years) and 27.4 years (SD, ±13.9 years) in PVRV and PCECV group, respectively. Bites were most often located on the lower extremities in both groups. The most common local adverse reaction in both groups was pain at the injection site (4%). Most of the reported systemic adverse reactions were headache (2.5%) and fever (1.9%) in PCECV and PVRV group, respectively. The incidence of itching was higher in the PVRV group compared to the PCECV group (1% vs. 0.1%) (P vaccination was associated with fewer itching at the injection site. There was no significant difference between PCECV and PVRV vaccine regarding local and systemic adverse reactions. Therefore, the PCECV vaccine can be administered instead of PVRV, when our country encounters serious challenges in PVRV vaccine supply.

  11. The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid β Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Akira Yano

    2015-01-01

    Full Text Available The reduction of brain amyloid beta (Aβ peptides by anti-Aβ antibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβ peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT induced anti-Aβ antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβ antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42 compared to Aβ fibrils. The levels of serum anti-Aβ antibodies and plasma Aβ peptides increased in both animals and decreased the brain Aβ40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβ antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβ peptides and their toxic effects via clearance of Aβ peptides by generated antibodies.

  12. Brucellosis vaccines for livestock.

    Science.gov (United States)

    Goodwin, Zakia I; Pascual, David W

    2016-11-15

    Brucellosis is a livestock disease responsible for fetal loss due to abortions. Worldwide, this disease has profound economic and social impact by reducing the ability of livestock producers to provide an adequate supply of disease-free meat and dairy products. In addition to its presence in domesticated animals, brucellosis is harbored in a number of wildlife species creating new disease reservoirs, which adds to the difficulty of eradicating this disease. Broad and consistent use of the available vaccines would contribute in reducing the incidence of brucellosis. Unfortunately, this practice is not common. In addition, the current brucellosis vaccines cannot provide sterilizing immunity, and in certain circumstances, vaccinated livestock are not protected against co-mingling Brucella-infected wildlife. Given that these vaccines are inadequate for conferring complete protection for some vaccinated livestock, alternatives are being sought, and these include genetic modifications of current vaccines or their reformulations. Alternatively, many groups have sought to develop new vaccines. Subunit vaccines, delivered as a combination of soluble vaccine plus adjuvant or the heterologous expression of Brucella epitopes by different vaccine vectors are currently being tested. New live attenuated Brucella vaccines are also being developed and tested in their natural hosts. Yet, what is rarely considered is the route of vaccination which could improve vaccine efficacy. Since Brucella infections are mostly transmitted mucosally, mucosal delivery of a vaccine has the potential of eliciting a more robust protective immune response for improved efficacy. Hence, this review will examine these questions and provide the status of new vaccines for livestock brucellosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Properties of a herpes simplex virus multiple immediate-early gene-deleted recombinant as a vaccine vector

    International Nuclear Information System (INIS)

    Watanabe, Daisuke; Brockman, Mark A.; Ndung'u, Thumbi; Mathews, Lydia; Lucas, William T.; Murphy, Cynthia G.; Felber, Barbara K.; Pavlakis, George N.; Deluca, Neal A.; Knipe, David M.

    2007-01-01

    Herpes simplex virus (HSV) recombinants induce durable immune responses in rhesus macaques and mice and have induced partial protection in rhesus macaques against mucosal challenge with virulent simian immunodeficiency virus (SIV). In this study, we evaluated the properties of a new generation HSV vaccine vector, an HSV-1 multiple immediate-early (IE) gene deletion mutant virus, d106, which contains deletions in the ICP4, ICP27, ICP22, and ICP47 genes. Because several of the HSV IE genes have been implicated in immune evasion, inactivation of the genes encoding these proteins was expected to result in enhanced immunogenicity. The d106 virus expresses few HSV gene products and shows minimal cytopathic effect in cultured cells. When d106 was inoculated into mice, viral DNA accumulated at high levels in draining lymph nodes, consistent with an ability to transduce dendritic cells and activate their maturation and movement to lymph nodes. A d106 recombinant expressing Escherichia coli β-galactosidase induced durable β-gal-specific IgG and CD8 + T cell responses in naive and HSV-immune mice. Finally, d106-based recombinants have been constructed that express simian immunodeficiency virus (SIV) gag, env, or a rev-tat-nef fusion protein for several days in cultured cells. Thus, d106 shows many of the properties desirable in a vaccine vector: limited expression of HSV gene products and cytopathogenicity, high level expression of transgenes, ability to induce durable immune responses, and an ability to transduce dendritic cells and induce their maturation and migration to lymph nodes

  14. Evolution of an Eurasian avian-like influenza virus in naïve and vaccinated pigs.

    Directory of Open Access Journals (Sweden)

    Pablo R Murcia

    Full Text Available Influenza viruses are characterized by an ability to cross species boundaries and evade host immunity, sometimes with devastating consequences. The 2009 pandemic of H1N1 influenza A virus highlights the importance of pigs in influenza emergence, particularly as intermediate hosts by which avian viruses adapt to mammals before emerging in humans. Although segment reassortment has commonly been associated with influenza emergence, an expanded host-range is also likely to be associated with the accumulation of specific beneficial point mutations. To better understand the mechanisms that shape the genetic diversity of avian-like viruses in pigs, we studied the evolutionary dynamics of an Eurasian Avian-like swine influenza virus (EA-SIV in naïve and vaccinated pigs linked by natural transmission. We analyzed multiple clones of the hemagglutinin 1 (HA1 gene derived from consecutive daily viral populations. Strikingly, we observed both transient and fixed changes in the consensus sequence along the transmission chain. Hence, the mutational spectrum of intra-host EA-SIV populations is highly dynamic and allele fixation can occur with extreme rapidity. In addition, mutations that could potentially alter host-range and antigenicity were transmitted between animals and mixed infections were commonplace, even in vaccinated pigs. Finally, we repeatedly detected distinct stop codons in virus samples from co-housed pigs, suggesting that they persisted within hosts and were transmitted among them. This implies that mutations that reduce viral fitness in one host, but which could lead to fitness benefits in a novel host, can circulate at low frequencies.

  15. Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as a Potential Candidate for a Malaria Vaccine.

    Science.gov (United States)

    Longley, Rhea J; Halbroth, Benedict R; Salman, Ahmed M; Ewer, Katie J; Hodgson, Susanne H; Janse, Chris J; Khan, Shahid M; Hill, Adrian V S; Spencer, Alexandra J

    2017-03-01

    Efforts are under way to improve the efficacy of subunit malaria vaccines through assessments of new adjuvants, vaccination platforms, and antigens. In this study, we further assessed the Plasmodium falciparum antigen upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3 was expressed in the viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) and used to immunize mice in a prime-boost regimen. We previously demonstrated that this regimen could provide partial protection against challenge with chimeric P. berghei parasites expressing PfUIS3. We now show that ChAd63-MVA PfUIS3 can also provide partial cross-species protection against challenge with wild-type P. berghei parasites. We also show that PfUIS3-specific cellular memory responses could be recalled in human volunteers exposed to P. falciparum parasites in a controlled human malaria infection study. When ChAd63-MVA PfUIS3 was coadministered with the vaccine candidate P. falciparum thrombospondin-related adhesion protein (PfTRAP) expressed in the ChAd63-MVA system, there was no significant change in immunogenicity to either vaccine. However, when mice were challenged with double chimeric P. berghei - P. falciparum parasites expressing both PfUIS3 and PfTRAP, vaccine efficacy was improved to 100% sterile protection. This synergistic effect was evident only when the two vaccines were mixed and administered at the same site. We have therefore demonstrated that vaccination with PfUIS3 can induce a consistent delay in patent parasitemia across mouse strains and against chimeric parasites expressing PfUIS3 as well as wild-type P. berghei ; when this vaccine is combined with another partially protective regimen (ChAd63-MVA PfTRAP), complete protection is induced. Copyright © 2017 Longley et al.

  16. Determinants of vaccine hesitancy

    Science.gov (United States)

    Braczkowska, Bogumiła; Kowalska, Małgorzata; Braczkowski, Ryszard; Barański, Kamil

    2017-01-01

    Vaccine hesitancy is a worrying phenomenon due to its range and health-related consequences. Secondary epidemiological data on the current situation of vaccination in Poland were analyzed. The source of the analyzed data were obtained from the reports of the National Sanitary Inspection and the National Institute of Public Health–National Institute of Hygiene in Warsaw. Legal basis on vaccination and the responsibilities of physicians related to these regulations were also discussed. Considering the opinions of ECDC experts, factors influencing vaccine hesitancy were identified. Attention was paid to the activities of the anti-vaccination movements, their range of activity and a strategy of action.

  17. Atypical Amniotic Fluid Embolism Managed with a Novel Therapeutic Regimen

    Directory of Open Access Journals (Sweden)

    Shadi Rezai

    2017-01-01

    Full Text Available Amniotic fluid embolism (AFE is the second leading cause of maternal mortality in the USA with an incidence of 1 : 15,200 births. The case fatality rate and perinatal mortality associated with AFE are 13–30% and 9–44%, respectively. This rare but devastating complication can be difficult to diagnose as many of the early signs and symptoms are nonspecific. Compounding this diagnostic challenge is a lack of effective treatment regimens which to date are mostly supportive. We present the case of a 26-year-old woman who suffered from suspected AFE and was successfully treated with the novel regimen of Atropine, Ondansetron, and Ketorolac (A-OK. The authors acknowledge that this case does not meet the new criteria proposed, by Clark in 2016, but feel that it is important to share this case report, due to dramatic patient response to the provided supportive therapy presented in this case report. We hope this case report will prompt further research into this novel approach to treating AFE with Atropine, Ondansetron, and Ketorolac.

  18. Late effects of various dose-fractionation regimens

    International Nuclear Information System (INIS)

    Turesson, I.; Notter, G.

    1983-01-01

    These clinical investigations of various dose-fractionation regimens on human skin show that: The late reactions cannot be predicted from the early reactions; The dose-response curves for late reactions are much steeper than for early reactions; Equivalent doses for various fractionation schedules concerning late effects can be calculated by means of a corrected CRE (NSD) formula; the correction must be considered preliminary because further follow-up is needed. A clinical fractionation study of this type requires: Extremely careful dosimetry; Study of the same anatomical region; Very long follow-up; Studies at different effect levels; Skin reaction is the only end point we have studied systematically for different fractionation regimens. Experience with the CRE formula as a model for calculating isoeffect doses for different fractionation schedules in routine clinical use can be summarized as follows: The CRE formula has been used prospectively since 1972 in all patients; CRE-equivalent weekly doses to 5 x 2.0 Gy per week has been used. (Although the fractionation schedule is changed, the overall treatment time is still the same); The CRE range was 18 to 21 for curative radiotherapy on carcinomas; No irradiation was applied during pronounced acute reactions. No unexpected complications have been observed under these conditions

  19. Accelerated split course regimen in the treatment of brain metastases

    International Nuclear Information System (INIS)

    Franchin, G.; Minatel, E.; Roncadin, M.; Trovo, M.G.; De Paoli, A.; Bortolus, R.; Arcicasa, M.; Boz, G.; Gobitti, C.; Grigoletto, E.; Bassignano, G.

    1988-01-01

    63 patients, with brain metastases were treated with an accelerated split course regimen; irradiation was given to the whole brain in 3 daily fractions of 160 cGy each for 5 days a week. The cycle was repeated after 2 weeks to a total dose of 4800 cGy. Male-female ratio was 3:1. Median age was 58 years. The most frequent site of primary tumor was lung (41 patients), breast in 6 patients, melanoma in 3 patients, other sites in 8 patients and unknown cancer in 5 patients. Thirty-five patients had multiple brain metastases localizations. Two patients failed to complete the scheduled treatment: one because of early death and the other by refusal of therapy during treatment. Complete remission was obtained in 4 patients and partial remission in 24 patients. The median survival time was 21 weeks. The overall response rate was 42.5%. Toxicity was not considerable. The treatment results were not influenced by the site of primary tumor or by disease spreading; only the neurologic status before radiotherapy and the response to treatment influenced survival. The results obtained are similar to those reported by others; however, with the accelerated split course regimen the treatment time was reduced and a shorter period of hospitalization was required. 36 refs.; 2 figs.; 3 tabs

  20. Repeated Courses of Rituximab in Chronic ITP: Three Different Regimens

    Science.gov (United States)

    Hasan, Aisha; Michel, Marc; Patel, Vivek; Stasi, Roberto; Cunningham-Rundles, Susanna; Leonard, John; Bussel, James

    2009-01-01

    This study investigated responses to re-treatment with rituximab in chronic ITP patients. Treatment with rituximab in chronic ITP patients induces long-lasting responses in approximately 30% of patients but even these patients may relapse. Twenty patients who had achieved a response to rituximab and relapsed were re-treated with rituximab (375 mg/m2 × 4); this data was analyzed retrospectively. Subsequently, 16 patients were prospectively randomized to receive rituximab with CVP (R-CVP) or double dose rituximab (DDR). Re- treatment with standard dose rituximab demonstrated responses similar to initial rituximab treatment in 15 of 20 patients. Neither of the 2 more intensive regimens (R-CVP, DDR) induced responses in any patient who had previously failed to respond to rituximab nor induced substantially longer-lasting responses among previous responders. No additional toxicity was noted with the DDR regimen, whereas R-CVP was not well tolerated. These results suggest that re-treatment with standard dose rituximab induces similar responses in 75% of previously responding patients and is well tolerated. Neither combining rituximab with CVP nor doubling the dose of rituximab increased the response rate. PMID:19731307

  1. Postcesarean Thromboprophylaxis with Two Different Regimens of Bemiparin

    Directory of Open Access Journals (Sweden)

    Milagros Cruz

    2011-01-01

    Full Text Available Objectives. To compare the effectiveness of postcesarean thromboprophylaxis with two different regimens of bemiparin. Material and Methods. The study included 646 women with cesarean delivery in our hospital within a 1-year period, randomly assigned to one of two groups for prophylaxis with 3500 IU bemiparin once daily for 5 days or 3500 IU bemiparin once daily for 10 days. Results. There was one case of pulmonary embolism (first day following cesarean. An additional risk factor was present in 98.52% of the women, most frequently emergency cesarean, anemia, or obesity. The only risk factors for thromboembolic disease significantly related to pulmonary thromboembolism were placental abruption and prematurity. There were no differences in thromboembolic events among the two thromboprophylaxis regimens. Conclusions. Cesarean-related thromboembolic events were reduced in our study population due to the thromboprophylactic measures taken. Thromboprophylaxis with 3500 IU bemiparin once daily for 5 days following cesarean was sufficient to avoid thromboembolic events.

  2. A Systematic Review of Recall Regimen and Maintenance Regimen of Patients with Dental Restorations. Part 2: Implant-Borne Restorations.

    Science.gov (United States)

    Bidra, Avinash S; Daubert, Diane M; Garcia, Lily T; Gauthier, Marissa F; Kosinski, Timothy F; Nenn, Conrad A; Olsen, John A; Platt, Jeffrey A; Wingrove, Susan S; Chandler, Nancy Deal; Curtis, Donald A

    2016-01-01

    To evaluate the current scientific evidence on patient recall and maintenance of implant-supported restorations, to standardize patient care regimens and improve maintenance of oral health. An additional purpose was to examine areas of deficiency in the current scientific literature and provide recommendations for future studies. An electronic search for articles in the English language literature from the past 10 years was performed independently by multiple investigators using a systematic search process. After application of predetermined inclusion and exclusion criteria, the final list of articles was reviewed to meet the objectives of this review. The initial electronic search resulted in 2816 titles. The systematic application of inclusion and exclusion criteria resulted in 14 articles that satisfied the study objectives. An additional 6 articles were added through a supplemental search process for a total of 20 studies. Of these, 11 were randomized controlled clinical trials, and 9 were observational studies. The majority of the studies (15 out of 20) were conducted in the past 5 years and most studies were conducted in Europe (15), followed by Asia (2), South America (1), the United States (1), and the Middle East (1). Results from the qualitative data on a combined 1088 patients indicated that outcome improvements in recall and maintenance regimen were related to (1) patient/treatment characteristic (type of prosthesis, type of prosthetic components, and type of restorative materials); (2) specific oral topical agents or oral hygiene aids (electric toothbrush, interdental brush, chlorhexidine, triclosan, water flossers) and (3) professional intervention (oral hygiene maintenance, and maintenance of the prosthesis). There is minimal evidence related to recall regimens in patients with implant-borne removable and fixed restorations; however, a considerable body of evidence indicates that patients with implant-borne removable and fixed restorations require

  3. Emerging Vaccine Informatics

    Directory of Open Access Journals (Sweden)

    Yongqun He

    2010-01-01

    Full Text Available Vaccine informatics is an emerging research area that focuses on development and applications of bioinformatics methods that can be used to facilitate every aspect of the preclinical, clinical, and postlicensure vaccine enterprises. Many immunoinformatics algorithms and resources have been developed to predict T- and B-cell immune epitopes for epitope vaccine development and protective immunity analysis. Vaccine protein candidates are predictable in silico from genome sequences using reverse vaccinology. Systematic transcriptomics and proteomics gene expression analyses facilitate rational vaccine design and identification of gene responses that are correlates of protection in vivo. Mathematical simulations have been used to model host-pathogen interactions and improve vaccine production and vaccination protocols. Computational methods have also been used for development of immunization registries or immunization information systems, assessment of vaccine safety and efficacy, and immunization modeling. Computational literature mining and databases effectively process, mine, and store large amounts of vaccine literature and data. Vaccine Ontology (VO has been initiated to integrate various vaccine data and support automated reasoning.

  4. 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.

  5. Pertussis vaccination in pregnancy.

    Science.gov (United States)

    Healy, C Mary

    2016-08-02

    Pertussis has had a resurgence with the highest incidence and complication rates in young infants, and deaths occurring mainly at Pertussis vaccination in pregnancy may protect infants through passive and active transfer of maternal antibodies that protect the infant until the primary immunization series. Studies show vaccinating pregnant women with acellular pertussis vaccine is safe for mother and infant, immunogenic with efficient transfer of antibodies to infants, and effective in preventing pertussis in young infants. Vaccine uptake in pregnant women is sub-optimal, but provider recommendation is the most important factor in improving vaccination rates. Studies are ongoing to determine the best timing of vaccination to protect infants, and into other strategies. Vaccinating pregnant women offers hope to prevent pertussis-related morbidity and mortality in infants worldwide.

  6. Vaccine epidemiology: A review

    Directory of Open Access Journals (Sweden)

    Chandrakant Lahariya

    2016-01-01

    Full Text Available This review article outlines the key concepts in vaccine epidemiology, such as basic reproductive numbers, force of infection, vaccine efficacy and effectiveness, vaccine failure, herd immunity, herd effect, epidemiological shift, disease modeling, and describes the application of this knowledge both at program levels and in the practice by family physicians, epidemiologists, and pediatricians. A case has been made for increased knowledge and understanding of vaccine epidemiology among key stakeholders including policy makers, immunization program managers, public health experts, pediatricians, family physicians, and other experts/individuals involved in immunization service delivery. It has been argued that knowledge of vaccine epidemiology which is likely to benefit the society through contributions to the informed decision-making and improving vaccination coverage in the low and middle income countries (LMICs. The article ends with suggestions for the provision of systematic training and learning platforms in vaccine epidemiology to save millions of preventable deaths and improve health outcomes through life-course.

  7. [Successful treatment with high-dose methotrexate/cytarabine regimen in a patient in SMILE regimen-resistant extranodal natural killer/T-cell lymphoma].

    Science.gov (United States)

    Saburi, Masuho; Itani, Kazuhito; Nagamatsu, Kentarou; Miyazaki, Yasuhiko; Otsuka, Eiichi; Urabe, Shogo; Saburi, Yoshio

    2014-01-01

    A 28-year-old man complained of pain in the oral mucosa and pharynx in March 2011, and then developed fever and generalized swelling of the cheek. In March 2012, a gum biopsy led to a diagnosis of extranodal natural killer/T-cell lymphoma (ENKL). (18)F-FDG-PET revealed significant uptake in the mouth, tonsils, jawbone, shoulder blade, humerus, ilium, femur, and spleen. After two courses of the SMILE (dexamethasone, methotrexate (MTX), ifosfamide, L-asparaginase, etoposide) regimen, the response was stable disease. However, a high-dose MTX/cytarabine (MA) regimen was effective. After three courses of the MA regimen, a partial response was achieved. Then, allogeneic bone marrow transplantation from an unrelated donor was performed. At 10 months after transplantation, there was no sign of recurrence. Although the optimal treatment for ENKL refractory to the SMILE regimen has yet to be established, our case suggests the MA regimen to be a potentially effective treatment option.

  8. Immunological evaluation of peptide vaccination for cancer patients with the HLA-A26 allele.

    Science.gov (United States)

    Sakamoto, Shinjiro; Matsueda, Satoko; Takamori, Shinzo; Toh, Uhi; Noguchi, Masanori; Yutani, Shigeru; Yamada, Akira; Shichijo, Shigeki; Yamada, Teppei; Suekane, Shigetaka; Kawano, Kouichiro; Sasada, Tetsuro; Hattori, Noboru; Kohno, Nobuoki; Itoh, Kyogo

    2015-10-01

    To develop a peptide vaccine for cancer patients with the HLA-A26 allele, which is a minor population worldwide, we investigated the immunological responses of HLA-A26(+) /A26(+) cancer patients to four different CTL epitope peptides under personalized peptide vaccine regimens. In personalized peptide vaccine regimens, two to four peptides showing positive peptide-specific IgG responses in pre-vaccination plasma were selected from the four peptide candidates applicable for HLA-A26(+) /A26(+) cancer patients and administered s.c. Peptide-specific CTL and IgG responses along with cytokine levels were measured before and after vaccination. Cell surface markers in PBMCs and plasma cytokine levels were also measured. In this study, 21 advanced cancer patients, including seven lung, three breast, two pancreas, and two colon cancer patients, were enrolled. Their HLA-A26 genotypes were HLA-A26:01 (n = 24), HLA-A26:03 (n = 10), and HLA-A26:02 (n = 8). One, 14, and 6 patients received two, three, and four peptides, respectively. Grade 1 or 2 skin reactions at the injection sites were observed in the majority of patients, but no severe adverse events related to the vaccination were observed. Peptide-specific CTL responses were augmented in 39% or 22% of patients after one or two cycles of vaccination, respectively. Notably, peptide-specific IgG were augmented in 63% or 100% of patients after one or two cycles of vaccination, respectively. Personalized peptide vaccines with these four CTL epitope peptides could be feasible for HLA-A26(+) advanced cancer patients because of their safety and higher rates of immunological responses. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  9. The effectiveness of preventative mass vaccination regimes against the incidence of highly pathogenic avian influenza on Java Island, Indonesia.

    Science.gov (United States)

    Bett, B; McLaws, M; Jost, C; Schoonman, L; Unger, F; Poole, J; Lapar, M L; Siregar, E S; Azhar, M; Hidayat, M M; Dunkle, S E; Mariner, J

    2015-04-01

    We conducted an operational research study involving backyard and semicommercial farms on Java Island, Indonesia, between April 2008 and September 2009 to evaluate the effectiveness of two preventive mass vaccination strategies against highly pathogenic avian influenza (HPAI). One regimen used Legok 2003 H5N1 vaccine, while the other used both Legok 2003 H5N1 and HB1 Newcastle disease (ND) vaccine. A total of 16 districts were involved in the study. The sample size was estimated using a formal power calculation technique that assumed a detectable effect of treatment as a 50% reduction in the baseline number of HPAI-compatible outbreaks. Within each district, candidate treatment blocks with village poultry populations ranging from 80 000 to 120 000 were created along subdistrict boundary lines. Subsequently, four of these blocks were randomly selected and assigned one treatment from a list that comprised control, vaccination against HPAI, vaccination against HPAI + ND. Four rounds of vaccination were administered at quarterly intervals beginning in July 2008. A vaccination campaign involved vaccinating 100 000 birds in a treatment block, followed by another 100 000 vaccinations 3 weeks later as a booster dose. Data on disease incidence and vaccination coverage were also collected at quarterly intervals using participatory epidemiological techniques. Compared with the unvaccinated (control) group, the incidence of HPAI-compatible events declined by 32% (P = 0.24) in the HPAI-vaccinated group and by 73% (P = 0.00) in the HPAI- and ND-vaccinated group. The effect of treatment did not vary with time or district. Similarly, an analysis of secondary data from the participatory disease and response (PDSR) database revealed that the incidence of HPAI declined by 12% in the HPAI-vaccinated group and by 24% in the HPAI + ND-vaccinated group. The results suggest that the HPAI + ND vaccination significantly reduced the incidence of HPAI-compatible events in mixed populations of

  10. Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation

    Directory of Open Access Journals (Sweden)

    Eun Kim

    2016-11-01

    Full Text Available Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV has raised global concern due to its association with a significant rise in the number of infants born with microcephaly and neurological disorders such as Guillain-Barré syndrome. We developed prototype subunit and adenoviral-based Zika vaccines encoding the extracellular portion of the ZIKV envelope gene (E fused to the T4 fibritin foldon trimerization domain (Efl. The subunit vaccine was delivered intradermally through carboxymethyl cellulose microneedle array (MNA. The immunogenicity of these two vaccines, named Ad5.ZIKV-Efl and ZIKV-rEfl, was tested in C57BL/6 mice. Prime/boost immunization regimen was associated with induction of a ZIKV-specific antibody response, which provided neutralizing immunity. Moreover, protection was evaluated in seven-day-old pups after virulent ZIKV intraperitoneal challenge. Pups born to mice immunized with Ad5.ZIKV-Efl were all protected against lethal challenge infection without weight loss or neurological signs, while pups born to dams immunized with MNA-ZIKV-rEfl were partially protected (50%. No protection was seen in pups born to phosphate buffered saline-immunized mice. This study illustrates the preliminary efficacy of the E ZIKV antigen vaccination in controlling ZIKV infectivity, providing a promising candidate vaccine and antigen format for the prevention of Zika virus disease.

  11. Non-Replicating Adenovirus-Vectored Anthrax Vaccine

    International Nuclear Information System (INIS)

    Van Kampen, K. R.; Zhang, J.; Jex, E.; Tang, D. C.

    2007-01-01

    As bioterrorism is emerging as a national threat, it is urgent to develop a new generation of anthrax vaccines that can be rapidly produced and mass administered in an emergency setting. We have demonstrated that protective immunity against anthrax spores could be elicited in mice by intranasal administration of a non-replicating human adenovirus serotype 5 (Ad5)-derived vector encoding Bacillus anthracis protective antigen (PA) in a single-dose regimen. The potency of an Ad5 vector encoding PA was remarkably enhanced by codon optimization of the PA gene to match the tRNA pool found in human cells. This nasal vaccine can be mass-administered by non-medical personnel during a bioterrorist attack. In addition, replication-competent adenovirus (RCA)-free Ad5-vectored anthrax vaccines can be mass produced in PER.C6 cells in serum-free wave bioreactors and purified by column chromatography to meet a surge in demand. The non-replicating nature of this new generation of anthrax vaccine ensures an excellent safety profile for vaccines and the environment.(author)

  12. [Mercury in vaccines].

    Science.gov (United States)

    Hessel, Luc

    2003-01-01

    Thiomersal, also called thimerosal, is an ethyl mercury derivative used as a preservative to prevent bacterial contamination of multidose vaccine vials after they have been opened. Exposure to low doses of thiomersal has essentially been associated with hypersensitivity reactions. Nevertheless there is no evidence that allergy to thiomersal could be induced by thiomersal-containing vaccines. Allergy to thiomersal is usually of delayed-hypersensitivity type, but its detection through cutaneous tests is not very reliable. Hypersensitivity to thiomersal is not considered as a contraindication to the use of thiomersal-containing vaccines. In 1999 in the USA, thiomersal was present in approximately 30 different childhood vaccines, whereas there were only 2 in France. Although there were no evidence of neurological toxicity in infants related to the use of thiomersal-containing vaccines, the FDA considered that the cumulative dose of mercury received by young infants following vaccination was high enough (although lower than the FDA threshold for methyl mercury) to request vaccine manufacturers to remove thiomersal from vaccine formulations. Since 2002, all childhood vaccines used in Europe and the USA are thiomersal-free or contain only minute amounts of thiomersal. Recently published studies have shown that the mercury levels in the blood, faeces and urine of children who had received thiomersal-containing vaccines were much lower than those accepted by the American Environmental Protection Agency. It has also been demonstrated that the elimination of mercury in children was much faster than what was expected on the basis of studies conducted with methyl mercury originating from food. Recently, the hypothesis that mercury contained in vaccines could be the cause of autism and other neurological developmental disorders created a new debate in the medical community and the general public. To date, none of the epidemiological studies conducted in Europe and elsewhere

  13. Genetically-barcoded SIV facilitates enumeration of rebound variants and estimation of reactivation rates in nonhuman primates following interruption of suppressive antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Christine M Fennessey

    2017-05-01

    Full Text Available HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads. However, this total viral load value represents the sum of many individual infection events, which are difficult to independently track using conventional sequencing approaches. To overcome this challenge, we generated a genetically tagged virus stock (SIVmac239M with a 34-base genetic barcode inserted between the vpx and vpr accessory genes of the infectious molecular clone SIVmac239. Next-generation sequencing of the virus stock identified at least 9,336 individual barcodes, or clonotypes, with an average genetic distance of 7 bases between any two barcodes. In vitro infection of rhesus CD4+ T cells and in vivo infection of rhesus macaques revealed levels of viral replication of SIVmac239M comparable to parental SIVmac239. After intravenous inoculation of 2.2x105 infectious units of SIVmac239M, an average of 1,247 barcodes were identified during acute infection in 26 infected rhesus macaques. Of the barcodes identified in the stock, at least 85.6% actively replicated in at least one animal, and on average each barcode was found in 5 monkeys. Four infected animals were treated with combination antiretroviral therapy (cART for 82 days starting on day 6 post-infection (study 1. Plasma viremia was reduced from >106 to <15 vRNA copies/mL by the time treatment was interrupted. Virus rapidly rebounded following treatment interruption and between 87 and 136 distinct clonotypes were detected in plasma at peak rebound viremia. This study confirmed that SIVmac239M viremia could be successfully curtailed with cART, and that upon cART discontinuation, rebounding viral variants could be identified and quantified. An additional 6 animals infected with SIVmac239M were treated with cART beginning on day 4 post-infection for 305, 374, or 482 days (study 2. Upon treatment interruption, between 4 and 8 distinct viral clonotypes were detected in each animal at peak rebound

  14. 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

  15. Heterologous HA DNA vaccine prime--inactivated influenza vaccine boost is more effective than using DNA or inactivated vaccine alone in eliciting antibody responses against H1 or H3 serotype influenza viruses.

    Science.gov (United States)

    Wang, Shixia; Parker, Chris; Taaffe, Jessica; Solórzano, Alicia; García-Sastre, Adolfo; Lu, Shan

    2008-07-04

    The trivalent inactivated vaccine (TIV) is used to prevent seasonal influenza virus infection in humans, however, the immunogenicity of this vaccine may be influenced by the priming effect of previous influenza vaccinations or exposure to antigenically related influenza viruses. The current study examines the immunogenicity of a clinically licensed TIV in rabbits naïve to influenza antigens. Animals were immunized with either the licensed TIV, a bivalent (H1 and H3) HA DNA vaccine or the combination of both. Temporal and peak level serum anti-influenza virus IgG responses were determined by enzyme-linked immunosorbent assay (ELISA). Functional antibody responses were measured by hemagglutination inhibition and microneutralization against either A/NewCaledonia//20/99 (H1N1) or A/Panama/2007/99 (H3N2) influenza viruses. Our results demonstrate that the immunogenicity of the TIV is low in sero-negative animals. More significantly, the heterologous DNA prime-TIV boost regimen was more immunogenic than the homologous prime-boost using either TIV or DNA vaccines alone. This finding justifies further investigation of HA DNA vaccines as a priming immunogen for the next generation of vaccines against seasonal or pandemic influenza virus infections.

  16. Development of immunity following financial incentives for hepatitis B vaccination among people who inject drugs: A randomized controlled trial.

    Science.gov (United States)

    Day, Carolyn A; Shanahan, Marian; Wand, Handan; Topp, Libby; Haber, Paul S; Rodgers, Craig; Deacon, Rachel; Walsh, Nick; Kaldor, John; van Beek, Ingrid; Maher, Lisa

    2016-01-01

    People who inject drugs (PWID) are at risk of hepatitis B virus (HBV) but have low rates of vaccination completion. The provision of modest financial incentives increases vaccination schedule completion, but their association with serological protection has yet to be determined. To investigate factors associated with vaccine-induced immunity among a sample of PWID randomly allocated to receive AUD$30 cash following receipt of doses two and three ('incentive condition') or standard care ('control condition') using an accelerated 3-dose (0,7,21 days) HBV vaccination schedule. A randomised controlled trial among PWID attending two inner-city health services and a field site in Sydney, Australia, assessing vaccine-induced immunity measured by hepatitis B surface antibodies (HBsAb ≥ 10 mIU/ml) at 12 weeks. The cost of the financial incentives and the provision of the vaccine program are also reported. Just over three-quarters of participants - 107/139 (77%)--completed the vaccination schedule and 79/139 (57%) were HBsAb ≥ 10 mIU/ml at 12 weeks. Vaccine series completion was the only variable significantly associated with vaccine-induced immunity in univariate analysis (62% vs 41%, pvaccination completion, provision of financial incentives was not associated with enhanced serological protection. Further research into factors which affect response rates and the optimal vaccination regimen and incentive schemes for this population are needed. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Paclitaxel and Carboplatin (TC) Regimen for Ovarian Cancer.

    Science.gov (United States)

    Akin, Julie M; Waddell, J Aubrey; Solimando, Dominic A

    2014-05-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

  18. nab-Paclitaxel Plus Gemcitabine Regimen for Pancreatic Cancer.

    Science.gov (United States)

    Porter, Courtney E; Waddell, J Aubrey; Solimando, Dominic A

    2014-01-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc, 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

  19. Antirelapse Efficacy of Various Primaquine Regimens for Plasmodium vivax

    Directory of Open Access Journals (Sweden)

    D. D. Rajgor

    2014-01-01

    respectively P=0.004. The relapse rate was 6.89%, 1.55%, 4%, and 3.85% as per the month of recurrence; 8.2%, 2%, 4.58%, and 3.68% P=0.007 as per PCR-RFLP; and 2.73%, 1.47%, 1.55%, and 1.53% as per PCR sequencing for groups A, B, C, and D, respectively. The concordance between methods was low, 45%. Conclusion. The higher recurrence rate in no PQ as compared to PQ groups documents PQ antirelapse activity. Regimens tested were safe. However, probable resistance to PQ warrants continuous monitoring and low concordance and limitations in the methods warrant caution in interpreting.

  20. Comparison of antiplatelet regimens in secondary stroke prevention

    DEFF Research Database (Denmark)

    Christiansen, Christine Benn; Pallisgaard, Jannik; Gerds, Thomas Alexander

    2015-01-01

    BACKGROUND: In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. The purpose of this study was to examine the risk of bleeding or recurrent...... were calculated for each antiplatelet regimen. RESULTS: Among patients discharged after first-time ischemic stroke, 3043 patients were treated with acetylsalicylic acid, 12,295 with a combination of acetylsalicylic acid and dipyridamole, and 3885 with clopidogrel. Adjusted HRs for clopidogrel versus...... the combination of acetylsalicylic acid and dipyridamole were 1.02 (95% confidence interval [CI]: 0.89-1.17) for ischemic stroke and 1.06 (95% CI: 0.83-1.35) for bleeding. Adjusted HRs for acetylsalicylic acid versus the combination of acetylsalicylic acid and dipyridamole were 1.48 (95% CI: 1.31-1.67) for stroke...

  1. Medication regimen complexity in ambulatory older adults with heart failure

    Directory of Open Access Journals (Sweden)

    Cobretti MR

    2017-04-01

    Full Text Available Michael R Cobretti,1 Robert L Page II,2 Sunny A Linnebur,2 Kimberly M Deininger,1 Amrut V Ambardekar,3 JoAnn Lindenfeld,4 Christina L Aquilante1 1Department of Pharmaceutical Sciences, 2Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 3Division of Cardiology, School of Medicine, University of Colorado, Aurora, CO, 4Advanced Heart Failure and Cardiac Transplant Program, Vanderbilt Heart and Vascular Institute, Nashville, TN, USA Purpose: Heart failure prevalence is increasing in older adults, and polypharmacy is a major problem in this population. We compared medication regimen complexity using the validated patient-level Medication Regimen Complexity Index (pMRCI tool in “young-old” (60–74 years versus “old-old” (75–89 years patients with heart failure. We also compared pMRCI between patients with ischemic cardiomyopathy (ISCM versus nonischemic cardiomyopathy (NISCM.Patients and methods: Medication lists were retrospectively abstracted from the electronic medical records of ambulatory patients aged 60–89 years with heart failure. Medications were categorized into three types – heart failure prescription medications, other prescription medications, and over-the-counter (OTC medications – and scored using the pMRCI tool.Results: The study evaluated 145 patients (n=80 young-old, n=65 old-old, n=85 ISCM, n=60 NISCM, mean age 73±7 years, 64% men, 81% Caucasian. Mean total pMRCI scores (32.1±14.4, range 3–84 and total medication counts (13.3±4.8, range 2–30 were high for the entire cohort, of which 72% of patients were taking eleven or more total medications. Total and subtype pMRCI scores and medication counts did not differ significantly between the young-old and old-old groups, with the exception of OTC medication pMRCI score (6.2±4 young-old versus 7.8±5.8 old-old, P=0.04. With regard to heart failure etiology, total pMRCI scores and medication

  2. Effectiveness of a sanguinarine regimen after scaling and root planing.

    Science.gov (United States)

    Tenenbaum, H; Dahan, M; Soell, M

    1999-03-01

    A variety of chemical agents have been evaluated relative to their abilities to inhibit dental plaque and to improve gingival health. Chlorhexidine gluconate is the best known and most widely used member of these agents, but its long-term use is compromised by different side effects, especially extrinsic tooth and tongue staining. Another agent, sanguinarine, which is currently used in both a mouthrinse and toothpaste, leads in some cases only to a transient burning sensation and could be used on a long-term basis. The purpose of this 14-week controlled clinical trial was to assess the effectiveness of a toothpaste and oral rinse containing sanguinaria extract after scaling, root planing and a chlorhexidine regimen. Sixty patients diagnosed as having adult periodontitis received initial periodontal therapy including scaling and root planing, followed by a 2-week oral care regimen which included rinsing with 0.2% chlorhexidine gluconate oral rinse. Upon completion of this 2-week initial therapy phase, patients were randomly assigned to either sanguinarine toothpaste and oral rinse or to control toothpaste and oral rinse without sanguinarine. Plaque (modified Quigley-Hein index) and gingivitis (gingival index) were measured prior to periodontal therapy, at the end of the chlorhexidine phase (2 weeks), and after 8 and 14 weeks. Sanguinarine-containing toothpaste and oral rinse significantly inhibited the redevelopment of gingivitis through the 12 weeks following the chlorhexidine phase compared to the control toothpaste and rinse. Patients in the test group had 26% fewer bleeding sites at 8 weeks, and 32% fewer at 14 weeks, than the control group. Our results support the combined use of chlorhexidine mouthrinse for a short term (2 weeks) followed by sanguinaria mouthrinse and toothpaste up to 3 months in order to optimize the effectiveness of chlorhexidine without side effects. Further studies on the long-term effect of this combination should be established.

  3. Introducción de la vacuna conjugada contra Hib en Chile y Uruguay Introducing Hib conjugate vaccine in Chile and Uruguay

    Directory of Open Access Journals (Sweden)

    Mauricio Landaverde

    1999-03-01

    Full Text Available In some countries, the invasive disease caused by Haemophilus influenzae type b (Hib has been practically eliminated thanks to vaccination. However, in much of the developing world, meningitides and pneumonias caused by these bacteria continue to be a major cause of childhood morbidity and mortality, as well as high hospitalization costs. Because safe and effective conjugate vaccines are now available, the Special Program for Vaccines and Immunization of the Pan American Health Organization has recommended introducing them into the regular vaccination regimen of as many countries as possible. This has been done in Chile and Uruguay, where the Hib vaccine now forms part of the regular vaccination routine. When the vaccine was being introduced, both countries had difficulties they could have avoided if they had known of the experiences of other nations. Therefore, these two countries now offer the lessons they learned to other nations considering introducing the vaccine into their immunization programs. The most important lessons were to: strengthen the epidemiological surveillance system sufficiently in advance of introducing the vaccine; with th support of sicentific societies, present the technical information that justifies introducing the vaccine; seek community backing and acceptance; precisely establish in advance the presentation and dosage of the vaccine that is most appropriate for the country; and be certain to have the political and legal decisions needed to ensure the continuity of Hib vaccination in the future.