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Sample records for monkeypox virus challenge

  1. Transmissibility of the monkeypox virus clades via respiratory transmission: investigation using the prairie dog-monkeypox virus challenge system.

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    Christina L Hutson

    Full Text Available Monkeypox virus (MPXV is endemic within Africa where it sporadically is reported to cause outbreaks of human disease. In 2003, an outbreak of human MPXV occurred in the US after the importation of infected African rodents. Since the eradication of smallpox (caused by an orthopoxvirus (OPXV related to MPXV and cessation of routine smallpox vaccination (with the live OPXV vaccinia, there is an increasing population of people susceptible to OPXV diseases. Previous studies have shown that the prairie dog MPXV model is a functional animal model for the study of systemic human OPXV illness. Studies with this model have demonstrated that infected animals are able to transmit the virus to naive animals through multiple routes of exposure causing subsequent infection, but were not able to prove that infected animals could transmit the virus exclusively via the respiratory route. Herein we used the model system to evaluate the hypothesis that the Congo Basin clade of MPXV is more easily transmitted, via respiratory route, than the West African clade. Using a small number of test animals, we show that transmission of viruses from each of the MPXV clade was minimal via respiratory transmission. However, transmissibility of the Congo Basin clade was slightly greater than West African MXPV clade (16.7% and 0% respectively. Based on these findings, respiratory transmission appears to be less efficient than those of previous studies assessing contact as a mechanism of transmission within the prairie dog MPXV animal model.

  2. Monkeypox

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    ... population. In recent animal studies of the prairie dog-human monkeypox model, two distinct clades of the virus ... new cases is critical for outbreak containment. Public health educational ... the risk of human-to-human transmission. Close physical contact with monkeypox ...

  3. Modified vaccinia virus Ankara protects macaques against respiratory challenge with monkeypox virus.

    NARCIS (Netherlands)

    K.J. Stittelaar (Koert); G. van Amerongen (Geert); I. Kondova (Ivanela); R.F. van Lavieren (Rob); F.H. Pistoor (Frank); H.G.M. Niesters (Bert); G.J.J. van Doornum (Gerard); B.A.M. van der Zeijst (Ben); L. Mateo (Luis); P.J. Chaplin (Paul); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

    2005-01-01

    textabstractThe use of classical smallpox vaccines based on vaccinia virus (VV) is associated with severe complications in both naive and immune individuals. Modified vaccinia virus Ankara (MVA), a highly attenuated replication-deficient strain of VV, has been proven to be safe in humans and immunoc

  4. Modified vaccinia virus Ankara protects macaques against respiratory challenge with monkeypox virus

    NARCIS (Netherlands)

    Stittelaar, Koert J; van Amerongen, Geert; Kondova, Ivanela; Kuiken, Thijs; van Lavieren, Rob F; Pistoor, Frank H M; Niesters, Hubert G M; van Doornum, Gerard; van der Zeijst, Ben A M; Mateo, Luis; Chaplin, Paul J; Osterhaus, Albert D M E

    2005-01-01

    The use of classical smallpox vaccines based on vaccinia virus (VV) is associated with severe complications in both naive and immune individuals. Modified vaccinia virus Ankara (MVA), a highly attenuated replication-deficient strain of VV, has been proven to be safe in humans and immunocompromised a

  5. Modified vaccinia virus Ankara protects macaques against respiratory challenge with monkeypox virus

    NARCIS (Netherlands)

    Stittelaar, Koert J; van Amerongen, Geert; Kondova, Ivanela; Kuiken, Thijs; van Lavieren, Rob F; Pistoor, Frank H M; Niesters, Hubert G M; van Doornum, Gerard; van der Zeijst, Ben A M; Mateo, Luis; Chaplin, Paul J; Osterhaus, Albert D M E

    2005-01-01

    The use of classical smallpox vaccines based on vaccinia virus (VV) is associated with severe complications in both naive and immune individuals. Modified vaccinia virus Ankara (MVA), a highly attenuated replication-deficient strain of VV, has been proven to be safe in humans and immunocompromised a

  6. Monkeypox virus: ecology and public health significance.

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    Khodakevich, L; Jezek, Z; Messinger, D

    1988-01-01

    Recent investigations have revealed that monkeypox virus infections occur with a high prevalence in several species of squirrels belonging to the genus Funisciurus, less frequently in squirrels of the genus Heliosciurus, and rarely in forest-dwelling primates. These squirrels commonly inhabit the secondary forests around human settlements in the rural areas of Zaire, especially where oil palms are grown, and are rare in the primary rain forest.Human infection with monkeypox virus occurs most frequently in the 5-9-year-old age group, particularly in small villages where the children hunt and eat squirrels and other small mammals. As the populations are now increasing in number and can no longer feed on wild life alone for their animal protein requirements, the development of animal husbandry as a source of meat will certainly decrease the risk and the incidence of human monkeypox, even in areas where monkeypox virus is present in the local population of squirrels.Although population growth and economic development in western and central Africa will probably reduce the risk of human infection with monkeypox virus, visitors to these areas who are likely to come into contact with wild animals should be offered smallpox vaccination as a protection.

  7. Inhalational Monkeypox Virus Infection in Cynomolgus Macaques

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    Roy eBarnewall

    2012-09-01

    Full Text Available An inhalation exposure system was characterized to deliver aerosolized monkeypox virus (MPXV, and a nonhuman primate (NHP inhalation monkeypox model was developed in cynomologus macaques. A head-only aerosol exposure system was characterized, and two sampling methods were evaluated: liquid impingement via an impinger and impaction via a gelatin filter. The aerosol concentrations obtained with the gelatin filter and impinger were virtually identical, indicating that either method is acceptable for sampling aerosols containing MPXV. The mass median aerodynamic diameter (MMAD was for individual aerosol tests in the aerosol system characterization and the NHP study ranged from 1.08 to 1.15 µm, indicating that the aerosol particles were of a sufficient size to reach the alveoli. Six cynomolgus macaques (four male and two female were used on study. The animals were aerosol exposed with MPXV and received doses between 2.51 x 104 to 9.28 x 105 plaque forming units (pfu inhaled. Four of the six animals died or were euthanized due to their moribund conditions. Both animals that received the lowest exposure doses survived to the end of the observation period. The inhalation LD50 was determined to be approximately 7.8 x 104 pfu inhaled. These data demonstrate that an inhalation MPXV infection model has been developed in the cynomolgus macaque with disease course and lethal dose similar to previously published data.

  8. Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease.

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    Mucker, Eric M; Chapman, Jennifer; Huzella, Louis M; Huggins, John W; Shamblin, Joshua; Robinson, Camenzind G; Hensley, Lisa E

    2015-01-01

    Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.

  9. Pathogenesis of fulminant monkeypox with bacterial sepsis after experimental infection with West African monkeypox virus in a cynomolgus monkey.

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    Nagata, Noriyo; Saijo, Masayuki; Kataoka, Michiyo; Ami, Yasushi; Suzaki, Yuriko; Sato, Yuko; Iwata-Yoshikawa, Naoko; Ogata, Momoko; Kurane, Ichiro; Morikawa, Shigeru; Sata, Tetsutaro; Hasegawa, Hideki

    2014-01-01

    The pathogenesis of severe human monkeypox, which causes systemic and fulminant infections, is not clear. This study presents a case repot of fulminant monkeypox with bacterial sepsis after experimental infection with monkeypox virus in a cynomolgus monkey (Macaca fascicularis). In our previous study (Saijo et al., 2009, J Gen Virol), two cynomolgus monkeys became moribund after experimental infection with monkeypox virus Liberia strain, West African strain. One exhibited typical monkeypox-related papulovesicular lesions. The other monkey presented fulminant clinical symptoms with a characteristic flat red rash similar to that found in smallpox, which is associated with extremely high fatality rates. In this study, we found that the monkey with flat red rash had high levels of viremia and neutropenia, as well as high plasma levels of pro-inflammatory cytokines and chemokines compared with the other monkey. Monkeypox virus replicates in epithelial cells and macrophages in various organs. Sepsis due to Gram-positive cocci was confirmed histopathologically in the monkey with flat red rash. The lack of inflammatory response in the lesion suggested that the monkey with sepsis experienced strong immune suppression during the viral infection. The neutropenia and excessive inflammatory cytokine responses indicate that neutrophils play key roles in the pathogenesis of systemic and fulminant human monkeypox virus infections with sepsis.

  10. In vitro inhibition of monkeypox virus production and spread by Interferon-β

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    Johnston Sara C

    2012-01-01

    Full Text Available Abstract Background The Orthopoxvirus genus contains numerous virus species that are capable of causing disease in humans, including variola virus (the etiological agent of smallpox, monkeypox virus, cowpox virus, and vaccinia virus (the prototypical member of the genus. Monkeypox is a zoonotic disease that is endemic in the Democratic Republic of the Congo and is characterized by systemic lesion development and prominent lymphadenopathy. Like variola virus, monkeypox virus is a high priority pathogen for therapeutic development due to its potential to cause serious disease with significant health impacts after zoonotic, accidental, or deliberate introduction into a naïve population. Results The purpose of this study was to investigate the prophylactic and therapeutic potential of interferon-β (IFN-β for use against monkeypox virus. We found that treatment with human IFN-β results in a significant decrease in monkeypox virus production and spread in vitro. IFN-β substantially inhibited monkeypox virus when introduced 6-8 h post infection, revealing its potential for use as a therapeutic. IFN-β induced the expression of the antiviral protein MxA in infected cells, and constitutive expression of MxA was shown to inhibit monkeypox virus infection. Conclusions Our results demonstrate the successful inhibition of monkeypox virus using human IFN-β and suggest that IFN-β could potentially serve as a novel safe therapeutic for human monkeypox disease.

  11. Susceptibility of Marmosets (Callithrix jacchus to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease.

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    Eric M Mucker

    Full Text Available Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units required to elicit a uniformly lethal disease and the extended incubation (preclinical signs are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.

  12. Laboratory Investigations of African Pouched Rats (Cricetomys gambianus as a Potential Reservoir Host Species for Monkeypox Virus.

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    Christina L Hutson

    Full Text Available Monkeypox is a zoonotic disease endemic to central and western Africa, where it is a major public health concern. Although Monkeypox virus (MPXV and monkeypox disease in humans have been well characterized, little is known about its natural history, or its maintenance in animal populations of sylvatic reservoir(s. In 2003, several species of rodents imported from Ghana were involved in a monkeypox outbreak in the United States with individuals of three African rodent genera (Cricetomys, Graphiurus, Funisciurus shown to be infected with MPXV. Here, we examine the course of MPXV infection in Cricetomys gambianus (pouched Gambian rats and this rodent species' competence as a host for the virus. We obtained ten Gambian rats from an introduced colony in Grassy Key, Florida and infected eight of these via scarification with a challenge dose of 4X104 plaque forming units (pfu from either of the two primary clades of MPXV: Congo Basin (C-MPXV: n = 4 or West African (W-MPXV: n = 4; an additional 2 animals served as PBS controls. Viral shedding and the effect of infection on activity and physiological aspects of the animals were measured. MPXV challenged animals had significantly higher core body temperatures, reduced activity and increased weight loss than PBS controls. Viable virus was found in samples taken from animals in both experimental groups (C-MPXV and W-MPXV between 3 and 27 days post infection (p.i. (up to 1X108 pfu/ml, with viral DNA found until day 56 p.i. The results from this work show that Cricetomys gambianus (and by inference, probably the closely related species, Cricetomys emini can be infected with MPXV and shed viable virus particles; thus suggesting that these animals may be involved in the maintenance of MPXV in wildlife mammalian populations. More research is needed to elucidate the epidemiology of MPXV and the role of Gambian rats and other species.

  13. Inhibition of Monkeypox virus replication by RNA interference

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    Jahrling Peter B

    2009-11-01

    Full Text Available Abstract The Orthopoxvirus genus of Poxviridae family is comprised of several human pathogens, including cowpox (CPXV, Vaccinia (VACV, monkeypox (MPV and Variola (VARV viruses. Species of this virus genus cause human diseases with various severities and outcome ranging from mild conditions to death in fulminating cases. Currently, vaccination is the only protective measure against infection with these viruses and no licensed antiviral drug therapy is available. In this study, we investigated the potential of RNA interference pathway (RNAi as a therapeutic approach for orthopox virus infections using MPV as a model. Based on genome-wide expression studies and bioinformatic analysis, we selected 12 viral genes and targeted them by small interference RNA (siRNA. Forty-eight siRNA constructs were developed and evaluated in vitro for their ability to inhibit viral replication. Two genes, each targeted with four different siRNA constructs in one pool, were limiting to viral replication. Seven siRNA constructs from these two pools, targeting either an essential gene for viral replication (A6R or an important gene in viral entry (E8L, inhibited viral replication in cell culture by 65-95% with no apparent cytotoxicity. Further analysis with wild-type and recombinant MPV expressing green fluorescence protein demonstrated that one of these constructs, siA6-a, was the most potent and inhibited viral replication for up to 7 days at a concentration of 10 nM. These results emphasis the essential role of A6R gene in viral replication, and demonstrate the potential of RNAi as a therapeutic approach for developing oligonucleotide-based drug therapy for MPV and other orthopox viruses.

  14. Comparison of monkeypox viruses pathogenesis in mice by in vivo imaging.

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    Jorge E Osorio

    Full Text Available Monkeypox viruses (MPXV cause human monkeypox, a zoonotic smallpox-like disease endemic to Africa, and are of worldwide public health and biodefense concern. Using viruses from the Congo (MPXV-2003-Congo-358 and West African (MPXV-2003-USA-044 clades, we constructed recombinant viruses that express the luciferase gene (MPXV-Congo/Luc+and MPXV-USA-Luc+ and compared their viral infection in mice by biophotonic imaging. BALB/c mice became infected by both MPXV clades, but they recovered and cleared the infection within 10 days post-infection (PI. However, infection in severe combined immune deficient (SCID BALB/c mice resulted in 100% lethality. Intraperitoneal (IP injection of both MPXV-Congo and MPXV-Congo/Luc+resulted in a systemic clinical disease and the same mean time-to-death at 9 (+/-0 days post-infection. Likewise, IP injection of SCID-BALB/c mice with MPXV-USA or the MPXV-USA-Luc+, resulted in similar disease but longer (P<0.05 mean time-to-death (11+/-0 days for both viruses compared to the Congo strains. Imaging studies in SCID mice showed luminescence in the abdomen within 24 hours PI with subsequent spread elsewhere. Animals infected with the MPXV-USA/Luc+had less intense luminescence in tissues than those inoculated with MPXV-Congo/Luc+, and systemic spread of the MPXV-USA/Luc+virus occurred approximately two days later than the MPXV-Congo/Luc+. The ovary was an important target for viral replication as evidenced by the high viral titers and immunohistochemistry. These studies demonstrate the suitability of a mouse model and biophotonic imaging to compare the disease progression and tissue tropism of MPX viruses.

  15. Comparison of monkeypox viruses pathogenesis in mice by in vivo imaging

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    Osorio, Jorge E.; Iams, Keith P.; Meteyer, Carol U.; Rocke, Tonie E.

    2009-01-01

    Monkeypox viruses (MPXV) cause human monkeypox, a zoonotic smallpox-like disease endemic to Africa, and are of worldwide public health and biodefense concern. Using viruses from the Congo (MPXV-2003-Congo-358) and West African (MPXV-2003-USA-044) clades, we constructed recombinant viruses that express the luciferase gene (MPXV-Congo/Luc+and MPXV-USA-Luc+) and compared their viral infection in mice by biophotonic imaging. BALB/c mice became infected by both MPXV clades, but they recovered and cleared the infection within 10 days post-infection (PI). However, infection in severe combined immune deficient (SCID) BALB/c mice resulted in 100% lethality. Intraperitoneal (IP) injection of both MPXV-Congo and MPXV-Congo/Luc+resulted in a systemic clinical disease and the same mean time-to-death at 9 (??0) days post-infection. Likewise, IP injection of SCID-BALB/c mice with MPXV-USA or the MPXV-USA-Luc+, resulted in similar disease but longer (Pluminescence in the abdomen within 24 hours PI with subsequent spread elsewhere. Animals infected with the MPXV-USA/Luc+had less intense luminescence in tissues than those inoculated with MPXV-Congo/Luc+, and systemic spread of the MPXV-USA/Luc+virus occurred approximately two days later than the MPXV-Congo/Luc+. The ovary was an important target for viral replication as evidenced by the high viral titers and immunohistochemistry. These studies demonstrate the suitability of a mouse model and biophotonic imaging to compare the disease progression and tissue tropism of MPX viruses.

  16. Characterization of Monkeypox virus infection in African rope squirrels (Funisciurus sp.)

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    Falendysz, Elizabeth; Lopera, Juan G.; Doty, Jeffrey B.; Nakazawa, Yoshinori J.; Crill, Colleen; Lorenzsonn, Faye; Kalemba, Lem's N.; Ronderos, Monica; Meija, Andres; Malekani, Jean M.; Karem, Kevin L.; Caroll, Darrin; Osorio, Jorge E.; Rocke, Tonie E.

    2017-01-01

    Monkeypox (MPX) is a zoonotic disease endemic in Central and West Africa and is caused by Monkeypox virus (MPXV), the most virulent Orthopoxvirus affecting humans since the eradication of Variola virus (VARV). Many aspects of the MPXV transmission cycle, including the natural host of the virus, remain unknown. African rope squirrels (Funisciurus spp.) are considered potential reservoirs of MPXV, as serosurveillance data in Central Africa has confirmed the circulation of the virus in these rodent species [1,2]. In order to understand the tissue tropism and clinical signs associated with infection with MPXV in these species, wild-caught rope squirrels were experimentally infected via intranasal and intradermal exposure with a recombinant MPXV strain from Central Africa engineered to express the luciferase gene. After infection, we monitored viral replication and shedding via in vivo bioluminescent imaging, viral culture and real time PCR. MPXV infection in African rope squirrels caused mortality and moderate to severe morbidity, with clinical signs including pox lesions in the skin, eyes, mouth and nose, dyspnea, and profuse nasal discharge. Both intranasal and intradermal exposures induced high levels of viremia, fast systemic spread, and long periods of viral shedding. Shedding and luminescence peaked at day 6 post infection and was still detectable after 15 days. Interestingly, one sentinel animal, housed in the same room but in a separate cage, also developed severe MPX disease and was euthanized. This study indicates that MPXV causes significant pathology in African rope squirrels and infected rope squirrels shed large quantities of virus, supporting their role as a potential source of MPXV transmission to humans and other animals in endemic MPX regions.

  17. Proteomic basis of the antibody response to monkeypox virus infection examined in cynomolgus macaques and a comparison to human smallpox vaccination.

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    Sarah Keasey

    Full Text Available Monkeypox is a zoonotic viral disease that occurs primarily in Central and West Africa. A recent outbreak in the United States heightened public health concerns for susceptible human populations. Vaccinating with vaccinia virus to prevent smallpox is also effective for monkeypox due to a high degree of sequence conservation. Yet, the identity of antigens within the monkeypox virus proteome contributing to immune responses has not been described in detail. We compared antibody responses to monkeypox virus infection and human smallpox vaccination by using a protein microarray covering 92-95% (166-192 proteins of representative proteomes from monkeypox viral clades of Central and West Africa, including 92% coverage (250 proteins of the vaccinia virus proteome as a reference orthopox vaccine. All viral gene clones were verified by sequencing and purified recombinant proteins were used to construct the microarray. Serum IgG of cynomolgus macaques that recovered from monkeypox recognized at least 23 separate proteins within the orthopox proteome, while only 14 of these proteins were recognized by IgG from vaccinated humans. There were 12 of 14 antigens detected by sera of human vaccinees that were also recognized by IgG from convalescent macaques. The greatest level of IgG binding for macaques occurred with the structural proteins F13L and A33R, and the membrane scaffold protein D13L. Significant IgM responses directed towards A44R, F13L and A33R of monkeypox virus were detected before onset of clinical symptoms in macaques. Thus, antibodies from vaccination recognized a small number of proteins shared with pathogenic virus strains, while recovery from infection also involved humoral responses to antigens uniquely recognized within the monkeypox virus proteome.

  18. Optimization of automated segmentation of monkeypox virus-induced lung lesions from normal lung CT images using hard C-means algorithm

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    Castro, Marcelo A.; Thomasson, David; Avila, Nilo A.; Hufton, Jennifer; Senseney, Justin; Johnson, Reed F.; Dyall, Julie

    2013-03-01

    Monkeypox virus is an emerging zoonotic pathogen that results in up to 10% mortality in humans. Knowledge of clinical manifestations and temporal progression of monkeypox disease is limited to data collected from rare outbreaks in remote regions of Central and West Africa. Clinical observations show that monkeypox infection resembles variola infection. Given the limited capability to study monkeypox disease in humans, characterization of the disease in animal models is required. A previous work focused on the identification of inflammatory patterns using PET/CT image modality in two non-human primates previously inoculated with the virus. In this work we extended techniques used in computer-aided detection of lung tumors to identify inflammatory lesions from monkeypox virus infection and their progression using CT images. Accurate estimation of partial volumes of lung lesions via segmentation is difficult because of poor discrimination between blood vessels, diseased regions, and outer structures. We used hard C-means algorithm in conjunction with landmark based registration to estimate the extent of monkeypox virus induced disease before inoculation and after disease progression. Automated estimation is in close agreement with manual segmentation.

  19. Evaluation of monkeypox virus infection of prairie dogs (Cynomys ludovicianus) using in vivo bioluminescent imaging

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    Falendysz, Elizabeth A.; Londoño-Navas, Angela M.; Meteyer, Carol U.; Pussini, Nicola; Lopera, Juan G.; Osorio, Jorge E.; Rocke, Tonie E.

    2014-01-01

    Monkeypox (MPX) is a re-emerging zoonotic disease that is endemic in Central and West Africa, where it can cause a smallpox-like disease in humans. Despite many epidemiologic and field investigations of MPX, no definitive reservoir species has been identified. Using recombinant viruses expressing the firefly luciferase (luc) gene, we previously demonstrated the suitability of in vivo bioluminescent imaging (BLI) to study the pathogenesis of MPX in animal models. Here, we evaluated BLI as a novel approach for tracking MPX virus infection in black-tailed prairie dogs (Cynomys ludovicianus). Prairie dogs were affected during a multistate outbreak of MPX in the US in 2003 and have since been used as an animal model of this disease. Our BLI results were compared with PCR and virus isolation from tissues collected postmortem. Virus was easily detected and quantified in skin and superficial tissues by BLI before and during clinical phases, as well as in subclinical secondary cases, but was not reliably detected in deep tissues such as the lung. Although there are limitations to viral detection in larger wild rodent species, BLI can enhance the use of prairie dogs as an animal model of MPX and can be used for the study of infection, disease progression, and transmission in potential wild rodent reservoirs.

  20. Monkeypox virus infection of rhesus macaques induces massive expansion of natural killer cells but suppresses natural killer cell functions.

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    Haifeng Song

    Full Text Available Natural killer (NK cells play critical roles in innate immunity and in bridging innate and adaptive immune responses against viral infection. However, the response of NK cells to monkeypox virus (MPXV infection is not well characterized. In this intravenous challenge study of MPXV infection in rhesus macaques (Macaca mulatta, we analyzed blood and lymph node NK cell changes in absolute cell numbers, cell proliferation, chemokine receptor expression, and cellular functions. Our results showed that the absolute number of total NK cells in the blood increased in response to MPXV infection at a magnitude of 23-fold, manifested by increases in CD56+, CD16+, CD16-CD56- double negative, and CD16+CD56+ double positive NK cell subsets. Similarly, the frequency and NK cell numbers in the lymph nodes also largely increased with the total NK cell number increasing 46.1-fold. NK cells both in the blood and lymph nodes massively proliferated in response to MPXV infection as measured by Ki67 expression. Chemokine receptor analysis revealed reduced expression of CXCR3, CCR7, and CCR6 on NK cells at early time points (days 2 and 4 after virus inoculation, followed by an increased expression of CXCR3 and CCR5 at later time points (days 7-8 of infection. In addition, MPXV infection impaired NK cell degranulation and ablated secretion of interferon-γ and tumor necrosis factor-α. Our data suggest a dynamic model by which NK cells respond to MPXV infection of rhesus macaques. Upon virus infection, NK cells proliferated robustly, resulting in massive increases in NK cell numbers. However, the migrating capacity of NK cells to tissues at early time points might be reduced, and the functions of cytotoxicity and cytokine secretion were largely compromised. Collectively, the data may explain, at least partially, the pathogenesis of MPXV infection in rhesus macaques.

  1. Further assessment of Monkeypox Virus infection in Gambian pouched rats (Cricetomys gambianus) using in vivo bioluminescent imaging

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    Falendysz, Elizabeth; Lopera, Juan G.; Faye Lorenzsonn,; Salzer, Johanna S.; Hutson, Christina L.; Doty, Jeffrey; Gallardo-Romero, Nadia; Carroll, Darin S.; Osorio, Jorge E.; Rocke, Tonie E.

    2015-01-01

    Monkeypox is a zoonosis clinically similar to smallpox in humans. Recent evidence has shown a potential risk of increased incidence in central Africa. Despite attempts to isolate the virus from wild rodents and other small mammals, no reservoir host has been identified. In 2003,Monkeypox virus (MPXV) was accidentally introduced into the U.S. via the pet trade and was associated with the Gambian pouched rat (Cricetomys gambianus). Therefore, we investigated the potential reservoir competence of the Gambian pouched rat for MPXV by utilizing a combination of in vivo and in vitro methods. We inoculated three animals by the intradermal route and three animals by the intranasal route, with one mock-infected control for each route. Bioluminescent imaging (BLI) was used to track replicating virus in infected animals and virological assays (e.g. real time PCR, cell culture) were used to determine viral load in blood, urine, ocular, nasal, oral, and rectal swabs. Intradermal inoculation resulted in clinical signs of monkeypox infection in two of three animals. One severely ill animal was euthanized and the other affected animal recovered. In contrast, intranasal inoculation resulted in subclinical infection in all three animals. All animals, regardless of apparent or inapparent infection, shed virus in oral and nasal secretions. Additionally, BLI identified viral replication in the skin without grossly visible lesions. These results suggest that Gambian pouched rats may play an important role in transmission of the virus to humans, as they are hunted for consumption and it is possible for MPXV-infected pouched rats to shed infectious virus without displaying overt clinical signs.

  2. Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection.

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    Berhanu, Aklile; Prigge, Jonathan T; Silvera, Peter M; Honeychurch, Kady M; Hruby, Dennis E; Grosenbach, Douglas W

    2015-07-01

    The therapeutic efficacies of smallpox vaccine ACAM2000 and antiviral tecovirimat given alone or in combination starting on day 3 postinfection were compared in a cynomolgus macaque model of lethal monkeypox virus infection. Postexposure administration of ACAM2000 alone did not provide any protection against severe monkeypox disease or mortality. In contrast, postexposure treatment with tecovirimat alone or in combination with ACAM2000 provided full protection. Additionally, tecovirimat treatment delayed until day 4, 5, or 6 postinfection was 83% (days 4 and 5) or 50% (day 6) effective.

  3. Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host-virus interactions

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    Ichou Mohamed

    2010-07-01

    Full Text Available Abstract Monkeypox virus (MPV is a zoonotic Orthopoxvirus and a potential biothreat agent that causes human disease with varying morbidity and mortality. Members of the Orthopoxvirus genus have been shown to suppress antiviral cell defenses, exploit host cell machinery, and delay infection-induced cell death. However, a comprehensive study of all host genes and virus-targeted host networks during infection is lacking. To better understand viral strategies adopted in manipulating routine host biology on global scale, we investigated the effect of MPV infection on Macaca mulatta kidney epithelial cells (MK2 using GeneChip rhesus macaque genome microarrays. Functional analysis of genes differentially expressed at 3 and 7 hours post infection showed distinctive regulation of canonical pathways and networks. While the majority of modulated histone-encoding genes exhibited sharp copy number increases, many of its transcription regulators were substantially suppressed; suggesting involvement of unknown viral factors in host histone expression. In agreement with known viral dependence on actin in motility, egress, and infection of adjacent cells, our results showed extensive regulation of genes usually involved in controlling actin expression dynamics. Similarly, a substantial ratio of genes contributing to cell cycle checkpoints exhibited concerted regulation that favors cell cycle progression in G1, S, G2 phases, but arrest cells in G2 phase and inhibits entry into mitosis. Moreover, the data showed that large number of infection-regulated genes is involved in molecular mechanisms characteristic of cancer canonical pathways. Interestingly, ten ion channels and transporters showed progressive suppression during the course of infection. Although the outcome of this unusual channel expression on cell osmotic homeostasis remains unknown, instability of cell osmotic balance and membrane potential has been implicated in intracellular pathogens egress. Our

  4. Poxvirus antigen staining of immune cells as a biomarker to predict disease outcome in monkeypox and cowpox virus infection in non-human primates.

    Directory of Open Access Journals (Sweden)

    Haifeng Song

    Full Text Available Infection of non-human primates (NHPs such as rhesus and cynomolgus macaques with monkeypox virus (MPXV or cowpox virus (CPXV serve as models to study poxvirus pathogenesis and to evaluate vaccines and anti-orthopox therapeutics. Intravenous inoculation of macaques with high dose of MPXV (>1-2×10(7 PFU or CPXV (>10(2 PFU results in 80% to 100% mortality and 66 to 100% mortality respectively. Here we report that NHPs with positive detection of poxvirus antigens in immune cells by flow cytometric staining, especially in monocytes and granulocytes succumbed to virus infection and that early positive pox staining is a strong predictor for lethality. Samples from four independent studies were analyzed. Eighteen NHPs from three different experiments were inoculated with two different MPXV strains at lethal doses. Ten NHPs displayed positive pox-staining and all 10 NHPs reached moribund endpoint. In contrast, none of the three NHPs that survived anticipated lethal virus dose showed apparent virus staining in the monocytes and granulocytes. In addition, three NHPs that were challenged with a lethal dose of MPXV and received cidofovir treatment were pox-antigen negative and all three NHPs survived. Furthermore, data from a CPXV study also demonstrated that 6/9 NHPs were pox-antigen staining positive and all 6 NHPs reached euthanasia endpoint, while the three survivors were pox-antigen staining negative. Thus, we conclude that monitoring pox-antigen staining in immune cells can be used as a biomarker to predict the prognosis of virus infection. Future studies should focus on the mechanisms and implications of the pox-infection of immune cells and the correlation between pox-antigen detection in immune cells and disease progression in human poxviral infection.

  5. Proteomic Basis of the Antibody Response to Monkeypox Virus Infection Examined in Cynomolgus Macaques and a Comparison to Human Smallpox Vaccination

    Science.gov (United States)

    2010-12-30

    from small - pox , was first observed in macaques no earlier than 6 days after initial infection. We first examined the antibody response during the...I, Jezek Z, Ladnyi ID (1988) Human monkeypox and other poxvirus infections of man In: Fenner F, ed. Small - pox and its Eradication. Geneva: World...virus were detected before onset of clinical symptoms in macaques. Thus, antibodies from vaccination recognized a small number of proteins shared with

  6. Ecological niche and geographic distribution of human monkeypox in Africa.

    Directory of Open Access Journals (Sweden)

    Rebecca S Levine

    Full Text Available Monkeypox virus, a zoonotic member of the genus Orthopoxviridae, can cause a severe, smallpox-like illness in humans. Monkeypox virus is thought to be endemic to forested areas of western and Central Africa. Considerably more is known about human monkeypox disease occurrence than about natural sylvatic cycles of this virus in non-human animal hosts. We use human monkeypox case data from Africa for 1970-2003 in an ecological niche modeling framework to construct predictive models of the ecological requirements and geographic distribution of monkeypox virus across West and Central Africa. Tests of internal predictive ability using different subsets of input data show the model to be highly robust and suggest that the distinct phylogenetic lineages of monkeypox in West Africa and Central Africa occupy similar ecological niches. High mean annual precipitation and low elevations were shown to be highly correlated with human monkeypox disease occurrence. The synthetic picture of the potential geographic distribution of human monkeypox in Africa resulting from this study should support ongoing epidemiologic and ecological studies, as well as help to guide public health intervention strategies to areas at highest risk for human monkeypox.

  7. Comparison of West African and Congo Basin monkeypox viruses in BALB/c and C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Christina L Hutson

    Full Text Available Although monkeypox virus (MPXV studies in wild rodents and non-human primates have generated important knowledge regarding MPXV pathogenesis and inferences about disease transmission, it might be easier to dissect the importance of virulence factors and correlates of protection to MPXV in an inbred mouse model. Herein, we compared the two clades of MPXV via two routes of infection in the BALB/c and C57BL/6 inbred mice strains. Our studies show that similar to previous animal studies, the Congo Basin strain of MPXV was more virulent than West African MPXV in both mouse strains as evidenced by clinical signs. Although animals did not develop lesions as seen in human MPX infections, localized signs were apparent with the foot pad route of inoculation, primarily in the form of edema at the site of inoculation; while the Congo Basin intranasal route of infection led to generalized symptoms, primarily weight loss. We have determined that future studies with MPXV and laboratory mice would be very beneficial in understanding the pathogenesis of MPXV, in particular if used in in vivo imaging studies. Although this mouse model may not suffice as a model of human MPX disease, with an appropriate inbred mouse model, we can unravel many unknown aspects of MPX pathogenesis, including virulence factors, disease progression in rodent hosts, and viral shedding from infected animals. In addition, such a model can be utilized to test antivirals and the next generation of orthopoxvirus vaccines for their ability to alter the course of disease.

  8. Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection

    NARCIS (Netherlands)

    Stittelaar, Koert J; Neyts, Johan; Naesens, Lieve; van Amerongen, Geert; van Lavieren, Rob F; Holý, Antonin; De Clercq, Erik; Niesters, Hubert G M; Fries, Edwin; Maas, Chantal; Mulder, Paul G H; van der Zeijst, Ben A M; Osterhaus, Albert D M E

    2006-01-01

    There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known ab

  9. Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection

    NARCIS (Netherlands)

    Stittelaar, Koert J; Neyts, Johan; Naesens, Lieve; van Amerongen, Geert; van Lavieren, Rob F; Holý, Antonin; De Clercq, Erik; Niesters, Hubert G M; Fries, Edwin; Maas, Chantal; Mulder, Paul G H; van der Zeijst, Ben A M; Osterhaus, Albert D M E

    2006-01-01

    There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known ab

  10. Generation and Characterization of a Double Recombinant Monkeypox Virus for use in Animal Model Development and Therapeutic Evaluation

    Science.gov (United States)

    2012-09-27

    by inhibiting the replication of influenza , measles, and specific 20     bunyaviruses (56). The effects of IFN- β on MxA induction as a...Center and School. 14. Di Giulio, D. B., and P. B. Eckburg. 2004. Human monkeypox: an emerging zoonosis . The Lancet infectious diseases 4:15-25

  11. Human monkeypox -- Kasai Oriental, Democratic Republic of Congo, February 1996-October 1997.

    Science.gov (United States)

    1997-12-12

    Human monkeypox is a severe smallpox-like illness caused by monkeypox virus (MPV); monkeypox occurs in sporadic outbreaks, and infection is enzootic among squirrels and monkeys in the rainforests of western and central Africa. In 1996, cases of monkeypox were reported from villages in the Katako-Kombe Health Zone, Kasai Oriental, Zaire (i.e., Democratic Republic of Congo). The World Health Organization (WHO), in collaboration with CDC, investigated this outbreak and identified 92 suspected cases with onset during February 1996-February 1997, and isolated MPV from lesions of active cases. Cases continued to be reported, and a new investigation was initiated by WHO and CDC in October 1997. This report summarizes the results of the field investigation, which indicate that this is the largest human monkeypox outbreak ever recorded.

  12. In vitro efficacy of ST246 against smallpox and monkeypox.

    Science.gov (United States)

    Smith, Scott K; Olson, Victoria A; Karem, Kevin L; Jordan, Robert; Hruby, Dennis E; Damon, Inger K

    2009-03-01

    Since the eradication of smallpox and the cessation of routine childhood vaccination for smallpox, the proportion of the world's population susceptible to infection with orthopoxviruses, such as variola virus (the causative agent of smallpox) and monkeypox virus, has grown substantially. In the United States, the only vaccines for smallpox licensed by the Food and Drug Administration (FDA) have been live virus vaccines. Unfortunately, a substantial number of people cannot receive live virus vaccines due to contraindications. Furthermore, no antiviral drugs have been fully approved by the FDA for the prevention or treatment of orthopoxvirus infection. Here, we show the inhibitory effect of one new antiviral compound, ST-246, on the in vitro growth properties of six variola virus strains and seven monkeypox virus strains. We performed multiple assays to monitor the cytopathic effect and to evaluate the reduction of viral progeny production and release in the presence of the compound. ST-246 had 50% effective concentrations of virus and <0.04 microM against monkeypox virus. In a dose-dependent manner, plaque size and comet tail formation were markedly reduced in the presence of the drug at low, noncytotoxic concentrations between 0.015 and 0.05 microM. Our in vitro phenotype data suggest that ST-246 inhibits variola and monkeypox viruses similarly by reducing the production and release of enveloped orthopoxvirus and support the development of ST-246 as an antiviral therapeutic compound for the treatment of severe systemic orthopoxvirus infections.

  13. Co-administration of the broad-spectrum antiviral, brincidofovir (CMX001), with smallpox vaccine does not compromise vaccine protection in mice challenged with ectromelia virus.

    Science.gov (United States)

    Parker, Scott; Crump, Ryan; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Lanier, E Randall; Painter, George; Schriewer, Jill; Trost, Lawrence C; Buller, R Mark

    2014-11-01

    Natural orthopoxvirus outbreaks such as vaccinia, cowpox, cattlepox and buffalopox continue to cause morbidity in the human population. Monkeypox virus remains a significant agent of morbidity and mortality in Africa. Furthermore, monkeypox virus's broad host-range and expanding environs make it of particular concern as an emerging human pathogen. Monkeypox virus and variola virus (the etiological agent of smallpox) are both potential agents of bioterrorism. The first line response to orthopoxvirus disease is through vaccination with first-generation and second-generation vaccines, such as Dryvax and ACAM2000. Although these vaccines provide excellent protection, their widespread use is impeded by the high level of adverse events associated with vaccination using live, attenuated virus. It is possible that vaccines could be used in combination with antiviral drugs to reduce the incidence and severity of vaccine-associated adverse events, or as a preventive in individuals with uncertain exposure status or contraindication to vaccination. We have used the intranasal mousepox (ectromelia) model to evaluate the efficacy of vaccination with Dryvax or ACAM2000 in conjunction with treatment using the broad spectrum antiviral, brincidofovir (BCV, CMX001). We found that co-treatment with BCV reduced the severity of vaccination-associated lesion development. Although the immune response to vaccination was quantifiably attenuated, vaccination combined with BCV treatment did not alter the development of full protective immunity, even when administered two days following ectromelia challenge. Studies with a non-replicating vaccine, ACAM3000 (MVA), confirmed that BCV's mechanism of attenuating the immune response following vaccination with live virus was, as expected, by limiting viral replication and not through inhibition of the immune system. These studies suggest that, in the setting of post-exposure prophylaxis, co-administration of BCV with vaccination should be considered

  14. Monkeypox disease transmission in an experimental setting: prairie dog animal model.

    Directory of Open Access Journals (Sweden)

    Christina L Hutson

    Full Text Available Monkeypox virus (MPXV is considered the most significant human public health threat in the genus Orthopoxvirus since the eradication of variola virus (the causative agent of smallpox. MPXV is a zoonotic agent endemic to forested areas of Central and Western Africa. In 2003, MPXV caused an outbreak in the United States due to the importation of infected African rodents, and subsequent sequential infection of North American prairie dogs (Cynomys ludovicianus and humans. In previous studies, the prairie dog MPXV model has successfully shown to be very useful for understanding MPXV since the model emulates key characteristics of human monkeypox disease. In humans, percutaneous exposure to animals has been documented but the primary method of human-to-human MPXV transmission is postulated to be by respiratory route. Only a few animal model studies of MPXV transmission have been reported. Herein, we show that MPXV infected prairie dogs are able to transmit the virus to naive animals through multiple transmission routes. All secondarily exposed animals were infected with MPXV during the course of the study. Notably, animals secondarily exposed appeared to manifest more severe disease; however, the disease course was very similar to those of experimentally challenged animals including inappetence leading to weight loss, development of lesions, production of orthopoxvirus antibodies and shedding of similar levels or in some instances higher levels of MPXV from the oral cavity. Disease was transmitted via exposure to contaminated bedding, co-housing, or respiratory secretions/nasal mucous (we could not definitively say that transmission occurred via respiratory route exclusively. Future use of the model will allow us to evaluate infection control measures, vaccines and antiviral strategies to decrease disease transmission.

  15. Outbreaks of human monkeypox after cessation of smallpox vaccination.

    Science.gov (United States)

    Reynolds, Mary G; Damon, Inger K

    2012-02-01

    The recent observation of a surge in human monkeypox in the Democratic Republic of the Congo (DRC) prompts the question of whether cessation of smallpox vaccination is driving the phenomenon, and if so, why is re-emergence not universal throughout the historic geographic range of the virus? Research addressing the virus's mechanisms for immune evasion and induction, as well as that directed at elucidating the genes involved in pathogenesis in different viral lineages (West African vs Congo Basin), provide insights to help explain why emergence appears to be geographically limited. Novel vaccines offer one solution to curtail the spread of this disease.

  16. Comparative Proteomics of Human Monkeypox and Vaccinia Intracellular Mature and Extracellular Enveloped Virions

    Energy Technology Data Exchange (ETDEWEB)

    Manes, Nathan P.; Estep, Ryan D.; Mottaz, Heather M.; Moore, Ronald J.; Clauss, Therese RW; Monroe, Matthew E.; Du, Xiuxia; Adkins, Joshua N.; Wong, Scott; Smith, Richard D.

    2008-03-07

    Orthopoxviruses are the largest and most complex of the animal viruses. In response to the recent emergence of monkeypox in Africa and the threat of smallpox bioterrorism, virulent (monkeypox virus) and benign (vaccinia virus) orthopoxviruses were proteomically compared with the goal of identifying proteins required for pathogenesis. Orthopoxviruses were grown in HeLa cells to two different viral forms (intracellular mature virus and extracellular enveloped virus), purified by sucrose gradient ultracentrifugation, denatured using RapiGest™ surfactant, and digested with trypsin. Unfractionated samples and strong cation exchange HPLC fractions were analyzed by reversed-phase LC-MS/MS, and analyses of the MS/MS spectra using SEQUEST® and X! Tandem resulted in the identification of hundreds of monkeypox, vaccinia, and copurified host proteins. The unfractionated samples were additionally analyzed by LC-MS on an LTQ-Orbitrap™, and the accurate mass and elution time tag approach was used to perform quantitative comparisons. Possible pathophysiological roles of differentially expressed orthopoxvirus genes are discussed.

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

    Science.gov (United States)

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

    2012-01-01

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

  18. Zika virus challenges for neuropsychiatry.

    Science.gov (United States)

    Simões E Silva, Ana Cristina; Moreira, Janaina Matos; Romanelli, Roberta Maia Castro; Teixeira, Antonio Lucio

    2016-01-01

    Before 2007, Zika virus (ZIKV) was generally considered as an arbovirus of low clinical relevance, causing a mild self-limiting febrile illness in tropical Africa and Southeast Asia. Currently, a large, ongoing outbreak of ZIKV that started in Brazil in 2015 is spreading across the Americas. Virus infection during pregnancy has been potentially linked to congenital malformations, including microcephaly. In addition to congenital malformations, a temporal association between ZIKV infection and an increase in cases of Guillain-Barré syndrome is currently being observed in several countries. The mechanisms underlying these neurological complications are still unknown. Emerging evidence, mainly from in vitro studies, suggests that ZIKV may have direct effects on neuronal cells. The aim of this study was to critically review the literature available regarding the neurobiology of ZIKV and its potential neuropsychiatric manifestations.

  19. Evaluation of the GeneXpert for Human Monkeypox Diagnosis

    Science.gov (United States)

    Li, Daniel; Wilkins, Kimberly; McCollum, Andrea M.; Osadebe, Lynda; Kabamba, Joelle; Nguete, Beatrice; Likafi, Toutou; Balilo, Marcel Pie; Lushima, Robert Shongo; Malekani, Jean; Damon, Inger K.; Vickery, Michael C. L.; Pukuta, Elisabeth; Nkawa, Frida; Karhemere, Stomy; Tamfum, Jean-Jacques Muyembe; Okitolonda, Emile Wemakoy; Li, Yu; Reynolds, Mary G.

    2017-01-01

    Monkeypox virus (MPXV), a zoonotic orthopoxvirus (OPX), is endemic in the Democratic Republic of Congo (DRC). Currently, diagnostic assays for human monkeypox (MPX) focus on real-time quantitative polymerase chain reaction (PCR) assays, which are typically performed in sophisticated laboratory settings. Herein, we evaluated the accuracy and utility of a multiplex MPX assay using the GeneXpert platform, a portable rapid diagnostic device that may serve as a point-of-care test to diagnose infections in endemic areas. The multiplex MPX/OPX assay includes a MPX-specific PCR test, OPX-generic PCR test, and an internal control PCR test. In total, 164 diagnostic specimens (50 crusts and 114 vesicular swabs) were collected from suspected MPX cases in Tshuapa Province, DRC, under national surveillance guidelines. The specimens were tested with the GeneXpert MPX/OPX assay and an OPX PCR assay at the Institut National de Recherche Biomedicale (INRB) in Kinshasa. Aliquots of each specimen were tested in parallel with a MPX-specific PCR assay at the Centers for Disease Control and Prevention. The results of the MPX PCR were used as the gold standard for all analyses. The GeneXpert MPX/OPX assay performed at INRB had a sensitivity of 98.8% and specificity of 100%. The GeneXpert assay performed well with both crust and vesicle samples. The GeneXpert MPX/OPX test incorporates a simple methodology that performs well in both laboratory and field conditions, suggesting its viability as a diagnostic platform that may expand and expedite current MPX detection capabilities. PMID:27994107

  20. Zika virus challenges for neuropsychiatry

    Directory of Open Access Journals (Sweden)

    Simões e Silva AC

    2016-07-01

    Full Text Available Ana Cristina Simões e Silva,1,2 Janaina Matos Moreira,1,2 Roberta Maia Castro Romanelli,2 Antonio Lucio Teixeira1,3 1Interdisciplinary Laboratory of Medical Investigation, 2Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG, Belo Horizonte, Brazil; 3Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA Abstract: Before 2007, Zika virus (ZIKV was generally considered as an arbovirus of low clinical relevance, causing a mild self-limiting febrile illness in tropical Africa and Southeast Asia. Currently, a large, ongoing outbreak of ZIKV that started in Brazil in 2015 is spreading across the Americas. Virus infection during pregnancy has been potentially linked to congenital malformations, including microcephaly. In addition to congenital malformations, a temporal association between ZIKV infection and an increase in cases of Guillain–Barré syndrome is currently being observed in several countries. The mechanisms underlying these neurological complications are still unknown. Emerging evidence, mainly from in vitro studies, suggests that ZIKV may have direct effects on neuronal cells. The aim of this study was to critically review the literature available regarding the neurobiology of ZIKV and its potential neuropsychiatric manifestations. Keywords: Zika virus, microcephaly, Guillain–Barré syndrome, neurodevelopmental disorders

  1. Zika virus, a pathway to new challenges.

    Science.gov (United States)

    Jamil, Zubia; Waheed, Yasir; Durrani, Taimoor Zeb

    2016-07-01

    The current Zika outbreak is largest of its kind with 1.4 million cases in Brazil alone. World Health Organization declared the current outbreak as the public health emergency of international concerns. The major route of Zika virus transmission is mosquito bites. Sexual transmission and monkey bites are also observed in few cases. There is dire need to evaluate the other routes of transmission like blood transfusion, lactation and contact with body fluids. Zika virus is infecting infants, not only causing microcephaly but also creating number of complications resulting in bad outcomes of pregnancy. In Brazil alone, 4000 cases of microcephaly have observed during the current outbreak. The incidence of Guillain-Barre (GB) syndrome is also observed during the current Zika virus outbreak. GB syndrome is acute medical condition leading the patients to death due to weakness of respiratory muscles or can cause the life time disability. There is no anti-viral drug or vaccine available for Zika virus. Zika infection can be prevented by using mosquito repellents, mosquito nets, cooling rooms by air conditions and wearing full sleeves or permethrin-treated clothes. The current outbreak of Zika has not only affected the health care but also caused great economic loss. Estimated loss in Latin America and Caribbean is US$3.5 billion. United Nation's sustainable development goal 3.d stresses the strengthening of early warning, risk reduction and management of national and global health risks. The world will keep on facing new challenges in the form of Ebola or Zika; there is strong need to prepare ourselves for any disease outbreak.

  2. Zika Virus: Emergence, Phylogenetics, Challenges, and Opportunities.

    Science.gov (United States)

    Rajah, Maaran M; Pardy, Ryan D; Condotta, Stephanie A; Richer, Martin J; Sagan, Selena M

    2016-11-11

    Zika virus (ZIKV) is an emerging arthropod-borne pathogen that has recently gained notoriety due to its rapid and ongoing geographic expansion and its novel association with neurological complications. Reports of ZIKV-associated Guillain-Barré syndrome as well as fetal microcephaly place emphasis on the need to develop preventative measures and therapeutics to combat ZIKV infection. Thus, it is imperative that models to study ZIKV replication and pathogenesis and the immune response are developed in conjunction with integrated vector control strategies to mount an efficient response to the pandemic. This paper summarizes the current state of knowledge on ZIKV, including the clinical features, phylogenetic analyses, pathogenesis, and the immune response to infection. Potential challenges in developing diagnostic tools, treatment, and prevention strategies are also discussed.

  3. Modified Vaccinia Ankara Virus Vaccination Provides Long-Term Protection against Nasal Rabbitpox Virus Challenge

    Science.gov (United States)

    Jones, Dorothy I.; McGee, Charles E.; Sample, Christopher J.; Sempowski, Gregory D.; Pickup, David J.

    2016-01-01

    Modified vaccinia Ankara virus (MVA) is a smallpox vaccine candidate. This study was performed to determine if MVA vaccination provides long-term protection against rabbitpox virus (RPXV) challenge, an animal model of smallpox. Two doses of MVA provided 100% protection against a lethal intranasal RPXV challenge administered 9 months after vaccination. PMID:27146001

  4. ESwab challenges influenza virus propagation in cell cultures

    DEFF Research Database (Denmark)

    Trebbien, Ramona; Andersen, B; Rønn, Jesper

    2014-01-01

    Although the ESwab kit (Copan, Brescia, Italy) is intended for sampling bacteria for culture, this kit is increasingly also used for virus sampling. The effect of ESwab medium on influenza virus detection by real-time reverse transcription-polymerase chain reaction (RT-PCR) or virus propagation...... in Madin-Darby canine kidney (MDCK) cell culture was investigated. The ESwab medium was suitable for viral RNA detection but not for viral propagation due to cytotoxicity. Sampling influenza viruses with ESwab challenges influenza surveillance by strongly limiting the possibility of antigenic...

  5. ESwab challenges influenza virus propagation in cell cultures

    DEFF Research Database (Denmark)

    Trebbien, Ramona; Andersen, B; Rønn, Jesper

    2014-01-01

    in Madin-Darby canine kidney (MDCK) cell culture was investigated. The ESwab medium was suitable for viral RNA detection but not for viral propagation due to cytotoxicity. Sampling influenza viruses with ESwab challenges influenza surveillance by strongly limiting the possibility of antigenic......Although the ESwab kit (Copan, Brescia, Italy) is intended for sampling bacteria for culture, this kit is increasingly also used for virus sampling. The effect of ESwab medium on influenza virus detection by real-time reverse transcription-polymerase chain reaction (RT-PCR) or virus propagation...

  6. Diagnostic Options and Challenges for Dengue and Chikungunya Viruses

    Directory of Open Access Journals (Sweden)

    Stacey K. Mardekian

    2015-01-01

    Full Text Available Dengue virus (DENV and Chikungunya virus (CHIKV are arboviruses that share the same Aedes mosquito vectors and thus overlap in their endemic areas. These two viruses also cause similar clinical presentations, especially in the initial stages of infection, with neither virus possessing any specific distinguishing clinical features. Because the outcomes and management strategies for these two viruses are vastly different, early and accurate diagnosis is imperative. Diagnosis is also important for surveillance, outbreak control, and research related to vaccine and drug development. Available diagnostic tests are aimed at detection of the virus, its antigenic components, or the host immune antibody response. In this review, we describe the recent progress and continued challenges related to the diagnosis of DENV and CHIKV infections.

  7. Diagnostic Options and Challenges for Dengue and Chikungunya Viruses.

    Science.gov (United States)

    Mardekian, Stacey K; Roberts, Amity L

    2015-01-01

    Dengue virus (DENV) and Chikungunya virus (CHIKV) are arboviruses that share the same Aedes mosquito vectors and thus overlap in their endemic areas. These two viruses also cause similar clinical presentations, especially in the initial stages of infection, with neither virus possessing any specific distinguishing clinical features. Because the outcomes and management strategies for these two viruses are vastly different, early and accurate diagnosis is imperative. Diagnosis is also important for surveillance, outbreak control, and research related to vaccine and drug development. Available diagnostic tests are aimed at detection of the virus, its antigenic components, or the host immune antibody response. In this review, we describe the recent progress and continued challenges related to the diagnosis of DENV and CHIKV infections.

  8. Zika Virus: Medical Countermeasure Development Challenges

    Science.gov (United States)

    Malone, Robert W.; Homan, Jane; Callahan, Michael V.; Glasspool-Malone, Jill; Damodaran, Lambodhar; Schneider, Adriano De Bernardi; Zimler, Rebecca; Talton, James; Cobb, Ronald R.; Ruzic, Ivan; Smith-Gagen, Julie; Janies, Daniel; Wilson, James

    2016-01-01

    Introduction Reports of high rates of primary microcephaly and Guillain–Barré syndrome associated with Zika virus infection in French Polynesia and Brazil have raised concerns that the virus circulating in these regions is a rapidly developing neuropathic, teratogenic, emerging infectious public health threat. There are no licensed medical countermeasures (vaccines, therapies or preventive drugs) available for Zika virus infection and disease. The Pan American Health Organization (PAHO) predicts that Zika virus will continue to spread and eventually reach all countries and territories in the Americas with endemic Aedes mosquitoes. This paper reviews the status of the Zika virus outbreak, including medical countermeasure options, with a focus on how the epidemiology, insect vectors, neuropathology, virology and immunology inform options and strategies available for medical countermeasure development and deployment. Methods Multiple information sources were employed to support the review. These included publically available literature, patents, official communications, English and Lusophone lay press. Online surveys were distributed to physicians in the US, Mexico and Argentina and responses analyzed. Computational epitope analysis as well as infectious disease outbreak modeling and forecasting were implemented. Field observations in Brazil were compiled and interviews conducted with public health officials. PMID:26934531

  9. Zika Virus: Medical Countermeasure Development Challenges.

    Science.gov (United States)

    Malone, Robert W; Homan, Jane; Callahan, Michael V; Glasspool-Malone, Jill; Damodaran, Lambodhar; Schneider, Adriano De Bernardi; Zimler, Rebecca; Talton, James; Cobb, Ronald R; Ruzic, Ivan; Smith-Gagen, Julie; Janies, Daniel; Wilson, James

    2016-03-01

    Reports of high rates of primary microcephaly and Guillain-Barré syndrome associated with Zika virus infection in French Polynesia and Brazil have raised concerns that the virus circulating in these regions is a rapidly developing neuropathic, teratogenic, emerging infectious public health threat. There are no licensed medical countermeasures (vaccines, therapies or preventive drugs) available for Zika virus infection and disease. The Pan American Health Organization (PAHO) predicts that Zika virus will continue to spread and eventually reach all countries and territories in the Americas with endemic Aedes mosquitoes. This paper reviews the status of the Zika virus outbreak, including medical countermeasure options, with a focus on how the epidemiology, insect vectors, neuropathology, virology and immunology inform options and strategies available for medical countermeasure development and deployment. Multiple information sources were employed to support the review. These included publically available literature, patents, official communications, English and Lusophone lay press. Online surveys were distributed to physicians in the US, Mexico and Argentina and responses analyzed. Computational epitope analysis as well as infectious disease outbreak modeling and forecasting were implemented. Field observations in Brazil were compiled and interviews conducted with public health officials.

  10. Zika Virus: Medical Countermeasure Development Challenges.

    Directory of Open Access Journals (Sweden)

    Robert W Malone

    2016-03-01

    Full Text Available Reports of high rates of primary microcephaly and Guillain-Barré syndrome associated with Zika virus infection in French Polynesia and Brazil have raised concerns that the virus circulating in these regions is a rapidly developing neuropathic, teratogenic, emerging infectious public health threat. There are no licensed medical countermeasures (vaccines, therapies or preventive drugs available for Zika virus infection and disease. The Pan American Health Organization (PAHO predicts that Zika virus will continue to spread and eventually reach all countries and territories in the Americas with endemic Aedes mosquitoes. This paper reviews the status of the Zika virus outbreak, including medical countermeasure options, with a focus on how the epidemiology, insect vectors, neuropathology, virology and immunology inform options and strategies available for medical countermeasure development and deployment.Multiple information sources were employed to support the review. These included publically available literature, patents, official communications, English and Lusophone lay press. Online surveys were distributed to physicians in the US, Mexico and Argentina and responses analyzed. Computational epitope analysis as well as infectious disease outbreak modeling and forecasting were implemented. Field observations in Brazil were compiled and interviews conducted with public health officials.

  11. Immunology of Bats and Their Viruses: Challenges and Opportunities

    Directory of Open Access Journals (Sweden)

    Tony Schountz

    2014-12-01

    Full Text Available Bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including Nipah virus, Marburg virus and rabies virus. They also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including SARS and MERS coronaviruses. As is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. Despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic agents, virtually nothing is known about the host/virus relationships; principally because few colonies of bats are available for experimental infections, a lack of reagents, methods and expertise for studying bat antiviral responses and immunology, and the difficulty of conducting meaningful field work. These challenges can be addressed, in part, with new technologies that are species-independent that can provide insight into the interactions of bats and viruses, which should clarify how the viruses persist in nature, and what risk factors might facilitate transmission to humans and livestock.

  12. Immunology of bats and their viruses: challenges and opportunities.

    Science.gov (United States)

    Schountz, Tony

    2014-12-01

    Bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including Nipah virus, Marburg virus and rabies virus. They also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including SARS and MERS coronaviruses. As is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. Despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic agents, virtually nothing is known about the host/virus relationships; principally because few colonies of bats are available for experimental infections, a lack of reagents, methods and expertise for studying bat antiviral responses and immunology, and the difficulty of conducting meaningful field work. These challenges can be addressed, in part, with new technologies that are species-independent that can provide insight into the interactions of bats and viruses, which should clarify how the viruses persist in nature, and what risk factors might facilitate transmission to humans and livestock.

  13. Acquisition Challenges of a Lethal Virus

    Science.gov (United States)

    2014-10-01

    virus is insect -borne. 27 Defense AT&L: September–October 2014 Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden...product in Tekmira’s TKM-Ebola, a drug candidate based on a gene- silencing technique used by plants and animals called RNA interference ( RNAi ...In the past decade, RNAi has become one of the most im- portant innovations in the field of drug discovery and de- velopment. In fact, in 2006 the

  14. Effects of georeferencing effort on mapping monkeypox case distributions and transmission risk

    Directory of Open Access Journals (Sweden)

    Lash R

    2012-06-01

    Full Text Available Abstract Background Maps of disease occurrences and GIS-based models of disease transmission risk are increasingly common, and both rely on georeferenced diseases data. Automated methods for georeferencing disease data have been widely studied for developed countries with rich sources of geographic referenced data. However, the transferability of these methods to countries without comparable geographic reference data, particularly when working with historical disease data, has not been as widely studied. Historically, precise geographic information about where individual cases occur has been collected and stored verbally, identifying specific locations using place names. Georeferencing historic data is challenging however, because it is difficult to find appropriate geographic reference data to match the place names to. Here, we assess the degree of care and research invested in converting textual descriptions of disease occurrence locations to numerical grid coordinates (latitude and longitude. Specifically, we develop three datasets from the same, original monkeypox disease occurrence data, with varying levels of care and effort: the first based on an automated web-service, the second improving on the first by reference to additional maps and digital gazetteers, and the third improving still more based on extensive consultation of legacy surveillance records that provided considerable additional information about each case. To illustrate the implications of these seemingly subtle improvements in data quality, we develop ecological niche models and predictive maps of monkeypox transmission risk based on each of the three occurrence data sets. Results We found macrogeographic variations in ecological niche models depending on the type of georeferencing method used. Less-careful georeferencing identified much smaller areas as having potential for monkeypox transmission in the Sahel region, as well as around the rim of the Congo Basin. These

  15. Recombinant measles virus vaccine expressing the Nipah virus glycoprotein protects against lethal Nipah virus challenge.

    Directory of Open Access Journals (Sweden)

    Misako Yoneda

    Full Text Available Nipah virus (NiV is a member of the genus Henipavirus, which emerged in Malaysia in 1998. In pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. Nipah virus has continued to re-emerge in Bangladesh and India, and person-to-person transmission appeared in the outbreak. Although a number of NiV vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. In this study, we have developed a recombinant measles virus (rMV vaccine expressing NiV envelope glycoproteins (rMV-HL-G and rMV-Ed-G. Vaccinated hamsters were completely protected against NiV challenge, while the mortality of unvaccinated control hamsters was 90%. We trialed our vaccine in a non-human primate model, African green monkeys. Upon intraperitoneal infection with NiV, monkeys showed several clinical signs of disease including severe depression, reduced ability to move and decreased food ingestion and died at 7 days post infection (dpi. Intranasal and oral inoculation induced similar clinical illness in monkeys, evident around 9 dpi, and resulted in a moribund stage around 14 dpi. Two monkeys immunized subcutaneously with rMV-Ed-G showed no clinical illness prior to euthanasia after challenge with NiV. Viral RNA was not detected in any organ samples collected from vaccinated monkeys, and no pathological changes were found upon histopathological examination. From our findings, we propose that rMV-NiV-G is an appropriate NiV vaccine candidate for use in humans.

  16. Recombinant measles virus vaccine expressing the Nipah virus glycoprotein protects against lethal Nipah virus challenge.

    Science.gov (United States)

    Yoneda, Misako; Georges-Courbot, Marie-Claude; Ikeda, Fusako; Ishii, Miho; Nagata, Noriyo; Jacquot, Frederic; Raoul, Hervé; Sato, Hiroki; Kai, Chieko

    2013-01-01

    Nipah virus (NiV) is a member of the genus Henipavirus, which emerged in Malaysia in 1998. In pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. Nipah virus has continued to re-emerge in Bangladesh and India, and person-to-person transmission appeared in the outbreak. Although a number of NiV vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. In this study, we have developed a recombinant measles virus (rMV) vaccine expressing NiV envelope glycoproteins (rMV-HL-G and rMV-Ed-G). Vaccinated hamsters were completely protected against NiV challenge, while the mortality of unvaccinated control hamsters was 90%. We trialed our vaccine in a non-human primate model, African green monkeys. Upon intraperitoneal infection with NiV, monkeys showed several clinical signs of disease including severe depression, reduced ability to move and decreased food ingestion and died at 7 days post infection (dpi). Intranasal and oral inoculation induced similar clinical illness in monkeys, evident around 9 dpi, and resulted in a moribund stage around 14 dpi. Two monkeys immunized subcutaneously with rMV-Ed-G showed no clinical illness prior to euthanasia after challenge with NiV. Viral RNA was not detected in any organ samples collected from vaccinated monkeys, and no pathological changes were found upon histopathological examination. From our findings, we propose that rMV-NiV-G is an appropriate NiV vaccine candidate for use in humans.

  17. Zika Virus: An Emerging Public Health Challenge

    Directory of Open Access Journals (Sweden)

    Sumeena Basundra

    2016-07-01

    Full Text Available Emerging infectious diseases comprise a substantial proportion of global morbidity and mortality. The world has been hit by Zika virus (ZIKV after it was able to surmount an effective public health response for its control. ZIKV disease is an emerging mosquitoborne disease which occurred as large outbreaks in Yap since 2007, Polynesia in 2013 and Brazil in 2015. ZIKV infection in pregnant women has been observed to be associated with congenital microcephaly with neurological and autoimmune sequelae in general population of Brazil. The incubation period of ZIKV varies from few days to weeks. Only 20% of infected cases have symptoms like any other arboviral illness. ZIKV is diagnosed using RT-PCR (reverse transcriptase-polymerase chain reaction and virus isolation from blood samples. The treatment comprises of relief of symptoms by conservative management with no specific vaccine being available. The prevention and control of ZIKV is based on reduction of vector density by Integrated Vector Management and personal protection measures. As per Indian scenario, Ministry of Health had issued guidelines based on effective surveillance, risk communication, laboratory and travel regulations. Approaches to such a potential global health security threat should be consistent, proactive, and should involve coordinated, multi-pronged, multilateral collaborative efforts since the concern is at the highest and immediate because of Global epidemic, Rio de Janeiro Olympic Games starting from Aug 5-21, 2016 and strong association with microcephaly. Most importantly the need of the hour is the development of vaccine for protection especially the young women who are in the reproductive age groups. The research for which is ongoing as far as the current situation of global epidemic response is concerned.

  18. Crop immunity against viruses: outcomes and future challenges.

    Science.gov (United States)

    Nicaise, Valérie

    2014-01-01

    Viruses cause epidemics on all major cultures of agronomic importance, representing a serious threat to global food security. As strict intracellular pathogens, they cannot be controlled chemically and prophylactic measures consist mainly in the destruction of infected plants and excessive pesticide applications to limit the population of vector organisms. A powerful alternative frequently employed in agriculture relies on the use of crop genetic resistances, approach that depends on mechanisms governing plant-virus interactions. Hence, knowledge related to the molecular bases of viral infections and crop resistances is key to face viral attacks in fields. Over the past 80 years, great advances have been made on our understanding of plant immunity against viruses. Although most of the known natural resistance genes have long been dominant R genes (encoding NBS-LRR proteins), a vast number of crop recessive resistance genes were cloned in the last decade, emphasizing another evolutive strategy to block viruses. In addition, the discovery of RNA interference pathways highlighted a very efficient antiviral system targeting the infectious agent at the nucleic acid level. Insidiously, plant viruses evolve and often acquire the ability to overcome the resistances employed by breeders. The development of efficient and durable resistances able to withstand the extreme genetic plasticity of viruses therefore represents a major challenge for the coming years. This review aims at describing some of the most devastating diseases caused by viruses on crops and summarizes current knowledge about plant-virus interactions, focusing on resistance mechanisms that prevent or limit viral infection in plants. In addition, I will discuss the current outcomes of the actions employed to control viral diseases in fields and the future investigations that need to be undertaken to develop sustainable broad-spectrum crop resistances against viruses.

  19. Early death after feline infectious peritonitis virus challenge due to recombinant vaccinia virus immunization.

    OpenAIRE

    Vennema, H.; de Groot, R J; Harbour, D. A.; Dalderup, M.; Gruffydd-Jones, T.; Horzinek, M.C.; Spaan, W J

    1990-01-01

    The gene encoding the fusogenic spike protein of the coronavirus causing feline infectious peritonitis was recombined into the genome of vaccinia virus. The recombinant induced spike-protein-specific, in vitro neutralizing antibodies in mice. When kittens were immunized with the recombinant, low titers of neutralizing antibodies were obtained. After challenge with feline infectious peritonitis virus, these animals succumbed earlier than did the control group immunized with wild-type vaccinia ...

  20. Oral Immunization with Recombinant Listeria monocytogenes Controls Virus Load after Vaginal Challenge with Feline Immunodeficiency Virus

    OpenAIRE

    Stevens, Rosemary; Howard, Kristina E.; Nordone, Sushila; Burkhard, MaryJo; Dean, Gregg A

    2004-01-01

    Recombinant Listeria monocytogenes has many attractive characteristics as a vaccine vector against human immunodeficiency virus (HIV). Wild-type and attenuated Listeria strains expressing HIV Gag have been shown to induce long-lived mucosal and systemic T-cell responses in mice. Using the feline immunodeficiency virus (FIV) model of HIV we evaluated recombinant L. monocytogenes in a challenge system. Five cats were immunized with recombinant L. monocytogenes that expresses the FIV Gag and del...

  1. Ectromelia Virus Infections of Mice as a Model to Support the Licensure of Anti-Orthopoxvirus Therapeutics

    Directory of Open Access Journals (Sweden)

    R. Mark Buller

    2010-09-01

    Full Text Available The absence of herd immunity to orthopoxviruses and the concern that variola or monkeypox viruses could be used for bioterroristic activities has stimulated the development of therapeutics and safer prophylactics. One major limitation in this process is the lack of accessible human orthopoxvirus infections for clinical efficacy trials; however, drug licensure can be based on orthopoxvirus animal challenge models as described in the “Animal Efficacy Rule”. One such challenge model uses ectromelia virus, an orthopoxvirus, whose natural host is the mouse and is the etiological agent of mousepox. The genetic similarity of ectromelia virus to variola and monkeypox viruses, the common features of the resulting disease, and the convenience of the mouse as a laboratory animal underscores its utility in the study of orthopoxvirus pathogenesis and in the development of therapeutics and prophylactics. In this review we outline how mousepox has been used as a model for smallpox. We also discuss mousepox in the context of mouse strain, route of infection, infectious dose, disease progression, and recovery from infection.

  2. Evaluation of dengue virus strains for human challenge studies.

    Science.gov (United States)

    Mammen, M P; Lyons, A; Innis, B L; Sun, W; McKinney, D; Chung, R C Y; Eckels, K H; Putnak, R; Kanesa-thasan, N; Scherer, J M; Statler, J; Asher, L V; Thomas, S J; Vaughn, D W

    2014-03-14

    Discordance between the measured levels of dengue virus neutralizing antibody and clinical outcomes in the first-ever efficacy study of a dengue tetravalent vaccine (Lancet, Nov 2012) suggests a need to re-evaluate the process of pre-screening dengue vaccine candidates to better predict clinical benefit prior to large-scale vaccine trials. In the absence of a reliable animal model and established correlates of protection for dengue, a human dengue virus challenge model may provide an approach to down-select vaccine candidates based on their ability to reduce risk of illness following dengue virus challenge. We report here the challenge of flavivirus-naïve adults with cell culture-passaged dengue viruses (DENV) in a controlled setting that resulted in uncomplicated dengue fever (DF). This sets the stage for proof-of-concept efficacy studies that allow the evaluation of dengue vaccine candidates in healthy adult volunteers using qualified DENV challenge strains well before they reach field efficacy trials involving children. Fifteen flavivirus-naïve adult volunteers received 1 of 7 DENV challenge strains (n=12) or placebo (n=3). Of the twelve volunteers who received challenge strains, five (two DENV-1 45AZ5 and three DENV-3 CH53489 cl24/28 recipients) developed DF, prospectively defined as ≥2 typical symptoms, ≥48h of sustained fever (>100.4°F) and concurrent viremia. Based on our study and historical data, we conclude that the DENV-1 and DENV-3 strains can be advanced as human challenge strains. Both of the DENV-2 strains and one DENV-4 strain failed to meet the protocol case definition of DF. The other two DENV-4 strains require additional testing as the illness approximated but did not satisfy the case definition of DF. Three volunteers exhibited effusions (1 pleural/ascites, 2 pericardial) and 1 volunteer exhibited features of dengue (rash, lymphadenopathy, neutropenia and thrombocytopenia), though in the absence of fever and symptoms. The occurrence of

  3. Mapping monkeypox transmission risk through time and space in the Congo Basin

    Science.gov (United States)

    Nakazawa, Yoshinori J.; Lash, R. Ryan; Carroll, Darin S.; Damon, Inger K.; Karem, Kevin L.; Reynolds, Mary G.; Osorio, Jorge E.; Rocke, Tonie E.; Malekani, Jean; Muyembe, Jean-Jacques; Formenty, Pierre; Peterson, A. Townsend

    2013-01-01

    Monkeypox is a major public health concern in the Congo Basin area, with changing patterns of human case occurrences reported in recent years. Whether this trend results from better surveillance and detection methods, reduced proportions of vaccinated vs. non-vaccinated human populations, or changing environmental conditions remains unclear. Our objective is to examine potential correlations between environment and transmission of monkeypox events in the Congo Basin. We created ecological niche models based on human cases reported in the Congo Basin by the World Health Organization at the end of the smallpox eradication campaign, in relation to remotely-sensed Normalized Difference Vegetation Index datasets from the same time period. These models predicted independent spatial subsets of monkeypox occurrences with high confidence; models were then projected onto parallel environmental datasets for the 2000s to create present-day monkeypox suitability maps. Recent trends in human monkeypox infection are associated with broad environmental changes across the Congo Basin. Our results demonstrate that ecological niche models provide useful tools for identification of areas suitable for transmission, even for poorly-known diseases like monkeypox.

  4. Pathogen-host associations and predicted range shifts of human monkeypox in response to climate change in central Africa.

    Directory of Open Access Journals (Sweden)

    Henri A Thomassen

    Full Text Available Climate change is predicted to result in changes in the geographic ranges and local prevalence of infectious diseases, either through direct effects on the pathogen, or indirectly through range shifts in vector and reservoir species. To better understand the occurrence of monkeypox virus (MPXV, an emerging Orthopoxvirus in humans, under contemporary and future climate conditions, we used ecological niche modeling techniques in conjunction with climate and remote-sensing variables. We first created spatially explicit probability distributions of its candidate reservoir species in Africa's Congo Basin. Reservoir species distributions were subsequently used to model current and projected future distributions of human monkeypox (MPX. Results indicate that forest clearing and climate are significant driving factors of the transmission of MPX from wildlife to humans under current climate conditions. Models under contemporary climate conditions performed well, as indicated by high values for the area under the receiver operator curve (AUC, and tests on spatially randomly and non-randomly omitted test data. Future projections were made on IPCC 4(th Assessment climate change scenarios for 2050 and 2080, ranging from more conservative to more aggressive, and representing the potential variation within which range shifts can be expected to occur. Future projections showed range shifts into regions where MPX has not been recorded previously. Increased suitability for MPX was predicted in eastern Democratic Republic of Congo. Models developed here are useful for identifying areas where environmental conditions may become more suitable for human MPX; targeting candidate reservoir species for future screening efforts; and prioritizing regions for future MPX surveillance efforts.

  5. Oral immunization with recombinant listeria monocytogenes controls virus load after vaginal challenge with feline immunodeficiency virus.

    Science.gov (United States)

    Stevens, Rosemary; Howard, Kristina E; Nordone, Sushila; Burkhard, MaryJo; Dean, Gregg A

    2004-08-01

    Recombinant Listeria monocytogenes has many attractive characteristics as a vaccine vector against human immunodeficiency virus (HIV). Wild-type and attenuated Listeria strains expressing HIV Gag have been shown to induce long-lived mucosal and systemic T-cell responses in mice. Using the feline immunodeficiency virus (FIV) model of HIV we evaluated recombinant L. monocytogenes in a challenge system. Five cats were immunized with recombinant L. monocytogenes that expresses the FIV Gag and delivers an FIV Env-expressing DNA vaccine (LMgag/pND14-Lc-env). Control cats were either sham immunized or immunized with wild-type L. monocytogenes (LM-wt). At 1 year after vaginal challenge, provirus could not be detected in any of the nine tissues evaluated from cats immunized with the recombinant bacteria but was detected in at least one tissue in 8 of 10 control animals. Virus was isolated from bone marrow of four of five LMgag/pND14-Lc-env-immunized cats by use of a stringent coculture system but required CD8(+) T-cell depletion, indicating CD8(+) T-cell suppression of virus replication. Control animals had an inverted CD4:CD8 ratio in mesenteric lymph node and were depleted of both CD4(+) and CD8(+) intestinal epithelial T cells, while LMgag/pND14-Lc-env-immunized animals showed no such abnormalities. Vaginal FIV-specific immunoglobulin A was present at high titer in three LMgag/pND14-Lc-env-immunized cats before challenge and in all five at 1 year postchallenge. This study demonstrates that recombinant L. monocytogenes conferred some control of viral load after vaginal challenge with FIV.

  6. Recombinant Measles Virus Vaccine Expressing the Nipah Virus Glycoprotein Protects against Lethal Nipah Virus Challenge

    OpenAIRE

    Misako Yoneda; Marie-Claude Georges-Courbot; Fusako Ikeda; Miho Ishii; Noriyo Nagata; Frederic Jacquot; Hervé Raoul; Hiroki Sato; Chieko Kai

    2013-01-01

    Nipah virus (NiV) is a member of the genus Henipavirus, which emerged in Malaysia in 1998. In pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. Nipah virus has continued to re-emerge in Bangladesh and India, and person-to-person transmission appeared in the outbreak. Although a number of NiV vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. In this study,...

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

    Directory of Open Access Journals (Sweden)

    Matthew T Aliota

    2016-12-01

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

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

    Science.gov (United States)

    Newman, Christina M.; Mohr, Emma L.; Gellerup, Dane D.; Breitbach, Meghan E.; Buechler, Connor R.; Rasheed, Mustafa N.; Mohns, Mariel S.; Weiler, Andrea M.; Barry, Gabrielle L.; Weisgrau, Kim L.; Eudailey, Josh A.; Rakasz, Eva G.; Vosler, Logan J.; Post, Jennifer; Capuano, Saverio; Golos, Thaddeus G.; Permar, Sallie R.; Osorio, Jorge E.; Friedrich, Thomas C.; O’Connor, Shelby L.; O’Connor, David H.

    2016-01-01

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

  9. One health, multiple challenges: The inter-species transmission of influenza A virus

    NARCIS (Netherlands)

    K.R. Short (Kirsty); M. Richard (Mathilde); J.H. Verhagen (Josanne); D.A.J. van Riel (Debby); E.J.A. Schrauwen (Eefje); J.M.A. van den Brand (Judith); B. Mänz (Benjamin); R. Bodewes (Rogier); S. Herfst (Sander)

    2015-01-01

    textabstractInfluenza A viruses are amongst the most challenging viruses that threaten both human and animal health. Influenza A viruses are unique in many ways. Firstly, they are unique in the diversity of host species that they infect. This includes waterfowl (the original reservoir), terrestrial

  10. One health, multiple challenges : The inter-species transmission of influenza A virus

    NARCIS (Netherlands)

    Short, Kirsty R; Richard, Mathilde; Verhagen, Josanne H; van Riel, Debby; Schrauwen, Eefje J A; van den Brand, Judith M A; Mänz, Benjamin; Bodewes, Rogier; Herfst, Sander

    2015-01-01

    Influenza A viruses are amongst the most challenging viruses that threaten both human and animal health. Influenza A viruses are unique in many ways. Firstly, they are unique in the diversity of host species that they infect. This includes waterfowl (the original reservoir), terrestrial and aquatic

  11. Effects of Newcastle disease virus vaccine antibodies on the shedding and transmission of challenge viruses.

    Science.gov (United States)

    Miller, Patti J; Afonso, Claudio L; El Attrache, John; Dorsey, Kristi M; Courtney, Sean C; Guo, Zijing; Kapczynski, Darrell R

    2013-12-01

    Different genotypes of avian paramyxovirus serotype-1 virus (APMV-1) circulate in many parts of the world. Traditionally, Newcastle disease virus (NDV) is recognized as having two major divisions represented by classes I and II, with class II being further divided into sixteen genotypes. Although all NDV are members of APMV-1 and are of one serotype, antigenic and genetic diversity is observed between the different genotypes. Reports of vaccine failure from many countries and reports by our lab on the reduced ability of classical vaccines to significantly decrease viral replication and shedding have created renewed interest in developing vaccines formulated with genotypes homologous to the virulent NDV (vNDV) circulating in the field. We assessed how the amount and specificity of humoral antibodies induced by inactivated vaccines affected viral replication, clinical protection and evaluated how non-homologous (heterologous) antibody levels induced by live NDV vaccines relate to transmission of vNDV. In an experimental setting, all inactivated NDV vaccines protected birds from morbidity and mortality, but higher and more specific levels of antibodies were required to significantly decrease viral replication. It was possible to significantly decrease viral replication and shedding with high levels of antibodies and those levels could be more easily reached with vaccines formulated with NDV of the same genotype as the challenge viruses. However, when the levels of heterologous antibodies were sufficiently high, it was possible to prevent transmission. As the level of humoral antibodies increase in vaccinated birds, the number of infected birds and the amount of vNDV shed decreased. Thus, in an experimental setting the effective levels of humoral antibodies could be increased by (1) increasing the homology of the vaccine to the challenge virus, or (2) allowing optimal time for the development of the immune response.

  12. Challenges in managing hepatitis C virus infection in cancer patients.

    Science.gov (United States)

    Borchardt, Roy A; Torres, Harrys A

    2014-03-21

    Cancer patients have unique problems associated with hepatitis C virus (HCV) infection and treatment not seen in the general population. HCV infection poses additional challenges and considerations for the management of cancer, and vice versa. HCV infection also can lead to the development of cancer, particularly hepatocellular carcinoma and non-Hodgkin lymphoma. In severely immunocompromised cancer patients, diagnosis of HCV infection requires increased reliance on RNA detection techniques. HCV infection can affect chemotherapy, and delay of HCV infection treatment until completion of chemotherapy and achievement of cancer remission may be required to decrease the potential for drug-drug interactions between antineoplastic agents and HCV therapeutics and potentiation of side effects of these agents. In addition, hematopoietic stem cell transplant (HSCT) recipients have an increased risk of early development of cirrhosis and fibrosis. Whether this increased risk applies to all patients regardless of cancer treatment is unknown. Furthermore, patients with cancer may have poorer sustained virological responses to HCV infection treatment than do those without cancer. Unfortunately, not all cancer patients are candidates for HCV infection therapy. In this article, we review the challenges in managing HCV infection in cancer patients and HSCT recipients.

  13. Low dose influenza virus challenge in the ferret leads to increased virus shedding and greater sensitivity to oseltamivir.

    Directory of Open Access Journals (Sweden)

    Anthony C Marriott

    Full Text Available Ferrets are widely used to study human influenza virus infection. Their airway physiology and cell receptor distribution makes them ideal for the analysis of pathogenesis and virus transmission, and for testing the efficacy of anti-influenza interventions and vaccines. The 2009 pandemic influenza virus (H1N1pdm09 induces mild to moderate respiratory disease in infected ferrets, following inoculation with 106 plaque-forming units (pfu of virus. We have demonstrated that reducing the challenge dose to 102 pfu delays the onset of clinical signs by 1 day, and results in a modest reduction in clinical signs, and a less rapid nasal cavity innate immune response. There was also a delay in virus production in the upper respiratory tract, this was up to 9-fold greater and virus shedding was prolonged. Progression of infection to the lower respiratory tract was not noticeably delayed by the reduction in virus challenge. A dose of 104 pfu gave an infection that was intermediate between those of the 106 pfu and 102 pfu doses. To address the hypothesis that using a more authentic low challenge dose would facilitate a more sensitive model for antiviral efficacy, we used the well-known neuraminidase inhibitor, oseltamivir. Oseltamivir-treated and untreated ferrets were challenged with high (106 pfu and low (102 pfu doses of influenza H1N1pdm09 virus. The low dose treated ferrets showed significant delays in innate immune response and virus shedding, delayed onset of pathological changes in the nasal cavity, and reduced pathological changes and viral RNA load in the lung, relative to untreated ferrets. Importantly, these observations were not seen in treated animals when the high dose challenge was used. In summary, low dose challenge gives a disease that more closely parallels the disease parameters of human influenza infection, and provides an improved pre-clinical model for the assessment of influenza therapeutics, and potentially, influenza vaccines.

  14. Recombinant rabies virus expressing the H protein of canine distemper virus protects dogs from the lethal distemper challenge.

    Science.gov (United States)

    Wang, Feng-Xue; Zhang, Shu-Qin; Zhu, Hong-Wei; Yang, Yong; Sun, Na; Tan, Bin; Li, Zhen-Guang; Cheng, Shi-Peng; Fu, Zhen F; Wen, Yong-Jun

    2014-12-05

    The rabies virus (RV) vector LBNSE expressing foreign antigens have shown considerable promise as vaccines against viral and bacteria diseases, which is effective and safe. We produced a new RV-based vaccine vehicle expressing 1.824 kb hemagglutinin (H) gene of the canine distemper virus (CDV) by reverse genetics technology. The recombinant virus LBNSE-CDV-H retained growth properties similar to those of vector LBNSE both in BSR and mNA cell culture. The H gene of CDV was expressed and detected by immunostaining. To compare the immunogenicity of LBNSE-CDV-H, dogs were immunized with each of these recombinant viruses by intramuscular (i.m.). The dogs were bled at third weeks after the immunization for the measurement of virus neutralizing antibody (VNA) and then challenged with virulent virus (ZJ 7) at fourth weeks. The parent virus (LBNSE) without expression of any foreign molecules was included for comparison. Dogs inoculated with LBNSE-CDV-H showed no any signs of disease and exhibited seroconversion against both RV and CDV H protein. The LBNSE-CDV-H did not cause disease in dogs and conferred protection from challenge with a lethal wild type CDV strain, demonstrating its potential value for wildlife conservation efforts. Together, these studies suggest that recombinant RV expressing H protein from CDV stimulated high levels of adaptive immune responses (VNA), and protected all dogs challenge infection.

  15. Acute infection with venezuelan equine encephalitis virus replicon particles catalyzes a systemic antiviral state and protects from lethal virus challenge.

    Science.gov (United States)

    Konopka, Jennifer L; Thompson, Joseph M; Whitmore, Alan C; Webb, Drue L; Johnston, Robert E

    2009-12-01

    The host innate immune response provides a critical first line of defense against invading pathogens, inducing an antiviral state to impede the spread of infection. While numerous studies have documented antiviral responses within actively infected tissues, few have described the earliest innate response induced systemically by infection. Here, utilizing Venezuelan equine encephalitis virus (VEE) replicon particles (VRP) to limit infection to the initially infected cells in vivo, a rapid activation of the antiviral response was demonstrated not only within the murine draining lymph node, where replication was confined, but also within distal tissues. In the liver and brain, expression of interferon-stimulated genes was detected by 1 to 3 h following VRP footpad inoculation, reaching peak expression of >100-fold over that in mock-infected animals. Moreover, mice receiving a VRP footpad inoculation 6, 12, or 24 h prior to an otherwise lethal VEE footpad challenge were completely protected from death, including a drastic reduction in challenge virus titers. VRP pretreatment also provided protection from intranasal VEE challenge and extended the average survival time following intracranial challenge. Signaling through the interferon receptor was necessary for antiviral gene induction and protection from VEE challenge. However, VRP pretreatment failed to protect mice from a heterologous, lethal challenge with vesicular stomatitis virus, yet conferred protection following challenge with influenza virus. Collectively, these results document a rapid modulation of the host innate response within hours of infection, capable of rapidly alerting the entire animal to pathogen invasion and leading to protection from viral disease.

  16. An inactivated whole-virus porcine parvovirus vaccine protects pigs against disease but does not prevent virus shedding even after homologous virus challenge.

    Science.gov (United States)

    Foerster, Tessa; Streck, André Felipe; Speck, Stephanie; Selbitz, Hans-Joachim; Lindner, Thomas; Truyen, Uwe

    2016-06-01

    Inactivated whole-virus vaccines against porcine parvovirus (PPV) can prevent disease but not infection and virus shedding after heterologous virus challenge. Here, we showed that the same is true for a homologous challenge. Pregnant sows were vaccinated with an experimental inactivated vaccine based on PPV strain 27a. They were challenged on day 40 of gestation with the virulent porcine parvovirus PPV-27a from which the vaccine was prepared (homologous challenge). On day 90 of gestation, the fetuses from vaccinated sows were protected against disease, while the fetuses of the non-vaccinated sows (control group) exhibited signs of parvovirus disease. All gilts, whether vaccinated or not vaccinated, showed a boost of PPV-specific antibodies indicative of virus infection and replication. Low DNA copy numbers, but not infectious virus, could be demonstrated in nasal or rectal swabs of immunized sows, but high copy numbers of challenge virus DNA as well as infectious virus could both be demonstrated in non-vaccinated sows.

  17. The challenges of avian influenza virus: mechanism, epidemiology and control

    Institute of Scientific and Technical Information of China (English)

    George F. GAO; Pang-Chui SHAW

    2009-01-01

    @@ Early 2009, eight human infection cases of H5N1 highly pathogenic avian influenza (HPAI) virus, with 5 death cases, were reported in China. This again made the world alert on a possible pandemic worldwide, probably caused by avian-origin influenza virus. Again H5N1 is in the spotlight of the world, not only for the scientists but also for the ordinary people. How much do we know about this virus? Where will this virus go and where did it come? Can we avoid a possible pandemic of influenza? Will the human beings conquer this devastating agent? Obviously we can list more questions than we know the answers.

  18. 'ANOTHER VECTOR BORNE CHALLENGE TO COMBAT- ZIKA VIRUS OUTBREAKS'.

    Science.gov (United States)

    Shoaib, Maria; Faraz, Ahmad; Ahmed, Syed Ahsanuddin

    2016-01-01

    Zika virus is a single-stranded RNA virus of the Flaviviridae family. It is known to transmit to humans primarily through the bite of an infected Aedes species mosquito which is also known to carry dengue, chikungunya & yellow fever virus. Transmission is anthroponotic (human-to-vector-to-human) during outbreaks, Perinatally in utero, sexually and via infected blood transfusion. It is mild and self-limiting infection lasting for several days to a week. However, it is suspected as a cause of Guillain Barre Syndrome. There is a teratogenic association of Zika virus causing congenital birth defects like microcephaly and neurologic abnormalities. Treatment is generally supportive and for symptomatic relief. No specific antiviral treatment or vaccine is yet available for Zika virus disease. It highlights importance of preventive public health measures at the community level and avoids travelling to the endemic areas.

  19. Apparent lack of effect of vaccination against mink enteritis virus (MEV). A challenge study

    DEFF Research Database (Denmark)

    Uttenthal, Åse

    1988-01-01

    The mink enteritis virus part of a triple vaccine was tested in mink. No raise in antibody response was measured after vaccination. Subsequent challenge of groups of vaccinated or not-vaccinated animals revealed no differences in virus excretion or antibody response in the different animals....

  20. Response of ponies to adjuvanted EHV-1 whole virus vaccine and challenge with virus of the homologous strain.

    Science.gov (United States)

    Dolby, C A; Hannant, D; Mumford, J A

    1995-01-01

    Five yearling ponies were vaccinated with inactivated Equid herpesvirus type 1 (EHV-1) in Freund's complete adjuvant as a double emulsion and revaccinated 6 weeks later with EHV-1 in Freund's incomplete adjuvant. These ponies and three age-matched controls were challenged intra-nasally after a further 6 weeks with homologous live virus and monitored clinically, biologically and serologically. After challenge, clinical signs were mild in both groups. No cell-associated viraemias were detected in vaccinated ponies. Vaccination induced high levels of complement-fixing (CF) and virus-neutralizing (VN) antibody, and elicited a response to all major viral glycoproteins as shown by western blot analysis.

  1. Schmallenberg virus infection of ruminants: challenges and opportunities for veterinarians

    Directory of Open Access Journals (Sweden)

    Claine F

    2015-06-01

    Full Text Available François Claine, Damien Coupeau, Laetitia Wiggers, Benoît Muylkens, Nathalie Kirschvink Veterinary Department, Faculty of Sciences, Namur Research Institute for Life Sciences (NARILIS, University of Namur (UNamur, Namur, Belgium Abstract: In 2011, European ruminant flocks were infected by Schmallenberg virus (SBV leading to transient disease in adult cattle but abortions and congenital deformities in calves, lambs, and goat kids. SBV belonging to the Simbu serogroup (family Bunyaviridae and genus Orthobunyavirus was first discovered in the same region where bluetongue virus serotype 8 (BTV-8 emerged 5 years before. Both viruses are transmitted by biting midges (Culicoides spp. and share several similarities. This paper describes the current knowledge of temporal and geographical spread, molecular virology, transmission and susceptible species, clinical signs, diagnosis, prevention and control, impact on ruminant health, and productivity of SBV infection in Europe, and compares SBV infection with BTV-8 infection in ruminants. Keywords: Schmallenberg virus, Europe, ruminants, review

  2. Mosquito-transmitted viruses - the great Brazilian challenge

    Directory of Open Access Journals (Sweden)

    Mânlio Tasso de Oliveira Mota

    Full Text Available ABSTRACT Arboviruses pose a serious threat to public health worldwide, overloading the healthcare system and causing economic losses. These viruses form a very diverse group, and in Brazil, arboviruses belonging to the families Flaviviridae and Togaviridae are predominant. Unfortunately, the number of arboviruses increases in proportion with factors such as deforestation, poor sanitation, climate changes, and introduction of new viruses like Chikungunya virus and Zika virus. In Brazil, dengue is endemic, along with the presence of other arboviruses. The situation is complicated by the scarcity of diagnostic infrastructure and the absence of approved vaccines for these diseases. Disease control, thus, relies solely on vector control. Therefore, enhanced clinical knowledge and improved general awareness about these arboviruses are indispensable to tackle diagnostic inadequacies.

  3. Possibility and Challenges of Conversion of Current Virus Species Names to Linnaean Binomials

    Energy Technology Data Exchange (ETDEWEB)

    Postler, Thomas S.; Clawson, Anna N.; Amarasinghe, Gaya K.; Basler, Christopher F.; Bavari, Sbina; Benkő, Mária; Blasdell, Kim R.; Briese, Thomas; Buchmeier, Michael J.; Bukreyev, Alexander; Calisher, Charles H.; Chandran, Kartik; Charrel, Rémi; Clegg, Christopher S.; Collins, Peter L.; Juan Carlos, De La Torre; Derisi, Joseph L.; Dietzgen, Ralf G.; Dolnik, Olga; Dürrwald, Ralf; Dye, John M.; Easton, Andrew J.; Emonet, Sébastian; Formenty, Pierre; Fouchier, Ron A. M.; Ghedin, Elodie; Gonzalez, Jean-Paul; Harrach, Balázs; Hewson, Roger; Horie, Masayuki; Jiāng, Dàohóng; Kobinger, Gary; Kondo, Hideki; Kropinski, Andrew M.; Krupovic, Mart; Kurath, Gael; Lamb, Robert A.; Leroy, Eric M.; Lukashevich, Igor S.; Maisner, Andrea; Mushegian, Arcady R.; Netesov, Sergey V.; Nowotny, Norbert; Patterson, Jean L.; Payne, Susan L.; PaWeska, Janusz T.; Peters, Clarence J.; Radoshitzky, Sheli R.; Rima, Bertus K.; Romanowski, Victor; Rubbenstroth, Dennis; Sabanadzovic, Sead; Sanfaçon, Hélène; Salvato, Maria S.; Schwemmle, Martin; Smither, Sophie J.; Stenglein, Mark D.; Stone, David M.; Takada, Ayato; Tesh, Robert B.; Tomonaga, Keizo; Tordo, Noël; Towner, Jonathan S.; Vasilakis, Nikos; Volchkov, Viktor E.; Wahl-Jensen, Victoria; Walker, Peter J.; Wang, Lin-Fa; Varsani, Arvind; Whitfield, Anna E.; Zerbini, F. Murilo; Kuhn, Jens H.

    2016-10-22

    Botanical, mycological, zoological, and prokaryotic species names follow the Linnaean format, consisting of an italicized Latinized binomen with a capitalized genus name and a lower case species epithet (e.g., Homo sapiens). Virus species names, however, do not follow a uniform format, and, even when binomial, are not Linnaean in style. In this thought exercise, we attempted to convert all currently official names of species included in the virus family Arenaviridae and the virus order Mononegavirales to Linnaean binomials, and to identify and address associated challenges and concerns. Surprisingly, this endeavor was not as complicated or time-consuming as even the authors of this article expected when conceiving the experiment. [Arenaviridae; binomials; ICTV; International Committee on Taxonomy of Viruses; Mononegavirales; virus nomenclature; virus taxonomy.

  4. Repeated challenge with virulent Newcastle Disease Virus does not decrease the efficacy of vaccines

    Science.gov (United States)

    In the field, well-vaccinated birds may be repeatedly exposed to challenges with virulent strains of Newcastle disease virus (vNDV), which may infect macrophages and cause damage to the immune system. In this study, we evaluated the hypothesis that daily challenges with high doses of vNDV may overwh...

  5. Genetic susceptibility to and presence of endogenous avian leukosis viruses impose no significant impact on survival days of chickens challenged with very virulent plus Marek's disease virus

    Science.gov (United States)

    Chicks of distinct genotypes at the tumor virus B locus (TVB) in combination with presence or absence of endogenous avian leukosis virus ev21 gene in their genomes were examined for survival day patterns after challenge with very virulent plus Marek’s disease virus (vv+MDV) in three consecutive tria...

  6. Infectious bronchitis virus S2 expressed from recombinant virus confers broad protection against challenge

    Science.gov (United States)

    We developed recombinant Newcastle disease virus (NDV) LaSota (rLS) expressing the IBV S2 gene (rLS/IBV.S2). The recombinant virus showed reduced pathogenicity compared to the parental LaSota strain but effectively elicited hemagglutination inhibition antibodies and protected chickens against lethal...

  7. Smallpox virus resequencing GeneChips can also rapidly ascertain species status for some zoonotic non-variola orthopoxviruses.

    Science.gov (United States)

    Sulaiman, Irshad M; Sammons, Scott A; Wohlhueter, Robert M

    2008-04-01

    We recently developed a set of seven resequencing GeneChips for the rapid sequencing of Variola virus strains in the WHO Repository of the Centers for Disease Control and Prevention. In this study, we attempted to hybridize these GeneChips with some known non-Variola orthopoxvirus isolates, including monkeypox, cowpox, and vaccinia viruses, for rapid detection.

  8. Zika virus: Global health challenge, threat and current situation.

    Science.gov (United States)

    Aziz, Hafsa; Zia, Aadarash; Anwer, Amania; Aziz, Muneeba; Fatima, Shazia; Faheem, Muhammad

    2017-06-01

    ZIKV has emerged as grave global health issue in the past few years. ZIKV was firstly isolated in 1947 from a rhesus sentinel monkey in the Zika forest in Uganda. It is usually transmitted by the bite of infected mosquitoes and infects skin fibroblasts, skin keratinocytes, etc. ZIKV until now was under reported because of its clinical similarity with the dengue and chikungunya. It is usually spread through the course of the sylvatic cycle. In this cycle, the virus or pathogen lifespan is spent between the wild animal and vectors. The intrinsic incubation period is not yet fully known but it is observed that the very first symptoms of ZIKV infection can appear or develop within 3-12 days of time period and usually subside within 7 days of time. There is a strong relationship between prenatal Zika virus infection and microcephaly; other serious brain anomalies to the infant or newborn are Guillain-Barré syndrome. To date no vaccines are available for ZIKV prevention hence only symptomatic treatment is recommended in infected patients. Usually ZIKV is detected by serologic (IgM ELISA), plaque reduction neutralization test (PRNT) along with in-house" molecular techniques (RT-PCR). ZIKV infection being imminent global health issue warrants strong protective measures to prevent it from becoming an epidemic. Early detection and prevention is the key to tackle this grave potential health hazard. J. Med. Virol. 89:943-951, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Vaccination with Venezuelan equine encephalitis replicons encoding cowpox virus structural proteins protects mice from intranasal cowpox virus challenge.

    Science.gov (United States)

    Thornburg, Natalie J; Ray, Caroline A; Collier, Martha L; Liao, Hua-Xin; Pickup, David J; Johnston, Robert E

    2007-06-05

    An anti-poxvirus vaccine based on replicon particles of Venezuelan equine encephalitis virus (VRP) is being developed. The cowpox virus genes encoding structural proteins corresponding to vaccinia virus proteins A33, B5, and A27 were each expressed from VRP. High serum IgG titers against these proteins were generated in BALB/c mice vaccinated with each of these VRP. VRP induced both IgG1 and IgG2a with a strong predominance of IgG2a production. The response is long-lasting, as evidenced by the retention of high anti-B5 serum IgG titers through at least 50 weeks after priming immunization. Mice vaccinated with B5-, A33- or A27-VRP individually or together survived intranasal challenge with cowpox virus, with the multivalent vaccine formulation providing more effective protection from weight loss and clinical signs of illness than the monovalent vaccines. These results demonstrate that VRP may provide an effective alternative to vaccinia virus vaccines against poxvirus infection.

  10. Simultaneous outbreaks of dengue, chikungunya and Zika virus infections: diagnosis challenge in a returning traveller with nonspecific febrile illness

    Directory of Open Access Journals (Sweden)

    E. Moulin

    2016-05-01

    Full Text Available Zika virus is an emerging flavivirus that is following the path of dengue and chikungunya. The three Aedes-borne viruses cause simultaneous outbreaks with similar clinical manifestations which represents a diagnostic challenge in ill returning travellers. We report the first Zika virus infection case imported to Switzerland and present a diagnostic algorithm.

  11. Vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses.

    Science.gov (United States)

    Geisbert, Thomas W; Daddario-Dicaprio, Kathleen M; Geisbert, Joan B; Reed, Douglas S; Feldmann, Friederike; Grolla, Allen; Ströher, Ute; Fritz, Elizabeth A; Hensley, Lisa E; Jones, Steven M; Feldmann, Heinz

    2008-12-09

    Considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against Ebola and Marburg viruses. A vaccine based on recombinant vesicular stomatitis virus (VSV) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. While filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of a bioterrorist event. At present, all candidate filoviral vaccines have been evaluated against parenteral challenges but none have been tested against an aerosol exposure. Here, we evaluated our recombinant VSV-based Zaire ebolavirus (ZEBOV) and Marburg virus (MARV) vaccines against aerosol challenge in cynomolgus macaques. All monkeys vaccinated with a VSV vector expressing the glycoprotein of ZEBOV were completely protected against an aerosol exposure of ZEBOV. Likewise, all monkeys vaccinated with a VSV vector expressing the glycoprotein of MARV were completely protected against an aerosol exposure of MARV. All control animals challenged by the aerosol route with either ZEBOV or MARV succumbed. Interestingly, disease in control animals appeared to progress slower than previously seen in macaques exposed to comparable doses by intramuscular injection.

  12. Challenges and Opportunities in Developing Respiratory Syncytial Virus Therapeutics

    NARCIS (Netherlands)

    Simoes, Eric A. F.; DeVincenzo, John P.; Boeckh, Michael; Bont, LJ; Crowe, James E.; Griffiths, Paul; Hayden, Frederick G.; Hodinka, Richard L.; Smyth, Rosalind L.; Spencer, Keith; Thirstrup, Steffen; Walsh, Edward E.; Whitley, Richard J.

    2015-01-01

    Two meetings, one sponsored by the Wellcome Trust in 2012 and the other by the Global Virology Foundation in 2013, assembled academic, public health and pharmaceutical industry experts to assess the challenges and opportunities for developing antivirals for the treatment of respiratory syncytial vir

  13. Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Highly Protective, Non-infectious Vaccine Against Ebola Virus Challenge

    Science.gov (United States)

    2016-07-01

    challenge 2 Nicholas J. Lennemann1, #, Andrew S. Herbert2, Rachel Brouillette1, Bethany Rhein1, Russell A. 3 Bakken2, Katherine J. Perschbacher1...vaccination regime protected mice against lethal challenge with mouse-adapted 27 Ebola virus (MA-EBOV) in a dose-dependent manner. As N-linked glycans are...effective immunity. High doses of GP/VSV partially or fully 30 denuded of N-linked glycans on GP1 protected mice against MA-EBOV challenge . However, 31

  14. H7N9 avian influenza A virus and the perpetual challenge of potential human pandemicity.

    Science.gov (United States)

    Morens, David M; Taubenberger, Jeffery K; Fauci, Anthony S

    2013-07-09

    ABSTRACT The ongoing H7N9 influenza epizootic in China once again presents us questions about the origin of pandemics and how to recognize them in early stages of development. Over the past ~135 years, H7 influenza viruses have neither caused pandemics nor been recognized as having undergone human adaptation. Yet several unusual properties of these viruses, including their poultry epizootic potential, mammalian adaptation, and atypical clinical syndromes in rarely infected humans, suggest that they may be different from other avian influenza viruses, thus questioning any assurance that the likelihood of human adaptation is low. At the same time, the H7N9 epizootic provides an opportunity to learn more about the mammalian/human adaptational capabilities of avian influenza viruses and challenges us to integrate virologic and public health research and surveillance at the animal-human interface.

  15. Addressing the next challenges: A summary of the 22nd international symposium on hepatitis C virus and related viruses.

    Science.gov (United States)

    Baumert, Thomas F; Schuster, Catherine; Cosset, François-Loïc; Dubuisson, Jean; Hofmann, Maike; Tautz, Norbert; Zeisel, Mirjam B; Thimme, Robert

    2016-04-01

    Following the discovery of the hepatitis C virus (HCV) more than 25 years ago the field has succeeded to develop methods that have changed the safety of blood products, understand the molecular virology, epidemiology and clinical disease of HCV, and identify specific targets for the development of direct-acting antivirals for HCV cure. Nevertheless, major clinical and scientific challenges remain: therapy is still only available to a fraction of infected patients worldwide and many patients remain undiagnosed and/or live in countries where therapy is unattainable. An urgently needed HCV vaccine to eradicate infection remains still elusive. Scientifically, major questions remain regarding the life cycle, pathogenesis and mechanisms of viral clearance and persistence. Addressing these challenges, this meeting report reviews key findings of the 22nd International Symposium on Hepatitis C Virus and Related Viruses in Strasbourg, France from October 9 to 13, 2015. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  16. Vaccination of hens decreases virus contamination in eggs after challenge with the virulent Newcastle disease virus

    Science.gov (United States)

    Newcastle disease is an important infectious disease of poultry causing economic losses worldwide. The control is routinely performed by vaccination, however vaccinated birds can shed virus, creating a barrier for trade exports. To determine if vaccination could mitigate these negative outcomes, h...

  17. Oncolytic viruses as immunotherapy: progress and remaining challenges

    Directory of Open Access Journals (Sweden)

    Aurelian L

    2016-05-01

    Full Text Available Laure Aurelian Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA Abstract: Oncolytic viruses (OVs comprise an emerging cancer therapeutic modality whose activity involves both direct tumor cell lysis and the induction of immunogenic cell death (ICD. Cellular proteins released from the OV-lysed tumor cells, known as damage-associated molecular patterns and tumor-associated antigens, activate dendritic cells and elicit adaptive antitumor immunity. Interaction with the innate immune system and the development of long-lasting immune memory also contribute to OV-induced cell death. The degree to which the ICD component contributes to the clinical efficacy of OV therapy is still unclear. Modulation of a range of immune interactions may be beneficial or detrimental in nature and the interactions depend on the specific tumor, the site and extent of the disease, the immunosuppressive tumor microenvironment, the OV platform, the dose, time, and delivery conditions, as well as individual patient responses. To enhance the contribution of ICD, OVs have been engineered to express immunostimulatory genes and strategies have been developed to combine OV therapy with chemo- and immune-based therapeutic regimens. However, these approaches carry the risk that they may also be tolerogenic depending on their levels and the presence of other cytokines, their direct antiviral effects, and the timing and conditions of their expression. The contribution of autophagy to adaptive immunity, the ability of the OVs to kill cancer stem cells, and the patient’s baseline immune status are additional considerations. This review focuses on the complex and as yet poorly understood balancing act that dictates the outcome of OV therapy. We summarize current understanding of the OVs’ function in eliciting antitumor immunity and its relationship to therapeutic efficacy. Also discussed are the criteria involved in restraining antiviral

  18. Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection.

    Directory of Open Access Journals (Sweden)

    Anthony C Marriott

    Full Text Available Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units. This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation and low to moderate doses (103 to 106 plaque forming units of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common influenza

  19. Preclinical assessment of HIV vaccines and microbicides by repeated low-dose virus challenges.

    Directory of Open Access Journals (Sweden)

    Roland R Regoes

    2005-08-01

    Full Text Available BACKGROUND: Trials in macaque models play an essential role in the evaluation of biomedical interventions that aim to prevent HIV infection, such as vaccines, microbicides, and systemic chemoprophylaxis. These trials are usually conducted with very high virus challenge doses that result in infection with certainty. However, these high challenge doses do not realistically reflect the low probability of HIV transmission in humans, and thus may rule out preventive interventions that could protect against "real life" exposures. The belief that experiments involving realistically low challenge doses require large numbers of animals has so far prevented the development of alternatives to using high challenge doses. METHODS AND FINDINGS: Using statistical power analysis, we investigate how many animals would be needed to conduct preclinical trials using low virus challenge doses. We show that experimental designs in which animals are repeatedly challenged with low doses do not require unfeasibly large numbers of animals to assess vaccine or microbicide success. CONCLUSION: Preclinical trials using repeated low-dose challenges represent a promising alternative approach to identify potential preventive interventions.

  20. A recombinant Hendra virus G glycoprotein-based subunit vaccine protects ferrets from lethal Hendra virus challenge.

    Science.gov (United States)

    Pallister, Jackie; Middleton, Deborah; Wang, Lin-Fa; Klein, Reuben; Haining, Jessica; Robinson, Rachel; Yamada, Manabu; White, John; Payne, Jean; Feng, Yan-Ru; Chan, Yee-Peng; Broder, Christopher C

    2011-08-01

    The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirrors the disease seen in humans and horses with induction of systemic vasculitis, including involvement of the pulmonary and central nervous systems. This model of HeV infection in the ferret was used to assess the immunogenicity and protective efficacy of a subunit vaccine based on a recombinant soluble version of the HeV attachment glycoprotein G (HeVsG), adjuvanted with CpG. We report that ferrets vaccinated with a 100 μg, 20 μg or 4 μg dose of HeVsG remained free of clinical signs of HeV infection following a challenge with 5000 TCID₅₀ of HeV. In addition, and of considerable importance, no evidence of virus or viral genome was detected in any tissues or body fluids in any ferret in the 100 and 20 μg groups, while genome was detected in the nasal washes only of one animal in the 4 μg group. Together, our findings indicate that 100 μg or 20 μg doses of HeVsG vaccine can completely prevent a productive HeV infection in the ferret, suggesting that vaccination to prevent the infection and shedding of HeV is possible.

  1. Deletion of virulence associated genes from attenuated African swine fever virus isolate OUR T88/3 decreases its ability to protect against challenge with virulent virus.

    Science.gov (United States)

    Abrams, Charles C; Goatley, Lynnette; Fishbourne, Emma; Chapman, David; Cooke, Lyndsay; Oura, Christopher A; Netherton, Christopher L; Takamatsu, Haru-Hisa; Dixon, Linda K

    2013-08-15

    African swine fever virus (ASFV) causes an acute haemorrhagic disease of domestic pigs against which there is no effective vaccine. The attenuated ASFV strain OUR T88/3 has been shown previously to protect vaccinated pigs against challenge with some virulent strains including OUR T88/1. Two genes, DP71L and DP96R were deleted from the OUR T88/3 genome to create recombinant virus OUR T88/3ΔDP2. Deletion of these genes from virulent viruses has previously been shown to reduce ASFV virulence in domestic pigs. Groups of 6 pigs were immunised with deletion virus OUR T88/3ΔDP2 or parental virus OUR T88/3 and challenged with virulent OUR T88/1 virus. Four pigs (66%) were protected by inoculation with the deletion virus OUR T88/3ΔDP2 compared to 100% protection with the parental virus OUR T88/3. Thus the deletion of the two genes DP71L and DP96R from OUR T88/3 strain reduced its ability to protect pigs against challenge with virulent virus.

  2. Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys.

    Science.gov (United States)

    Abbink, Peter; Larocca, Rafael A; De La Barrera, Rafael A; Bricault, Christine A; Moseley, Edward T; Boyd, Michael; Kirilova, Marinela; Li, Zhenfeng; Ng'ang'a, David; Nanayakkara, Ovini; Nityanandam, Ramya; Mercado, Noe B; Borducchi, Erica N; Agarwal, Arshi; Brinkman, Amanda L; Cabral, Crystal; Chandrashekar, Abishek; Giglio, Patricia B; Jetton, David; Jimenez, Jessica; Lee, Benjamin C; Mojta, Shanell; Molloy, Katherine; Shetty, Mayuri; Neubauer, George H; Stephenson, Kathryn E; Peron, Jean Pierre S; Zanotto, Paolo M de A; Misamore, Johnathan; Finneyfrock, Brad; Lewis, Mark G; Alter, Galit; Modjarrad, Kayvon; Jarman, Richard G; Eckels, Kenneth H; Michael, Nelson L; Thomas, Stephen J; Barouch, Dan H

    2016-09-09

    Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and has been causally associated with fetal microcephaly. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Here we demonstrate that three different vaccine platforms protect against ZIKV challenge in rhesus monkeys. A purified inactivated virus vaccine induced ZIKV-specific neutralizing antibodies and completely protected monkeys against ZIKV strains from both Brazil and Puerto Rico. Purified immunoglobulin from vaccinated monkeys also conferred passive protection in adoptive transfer studies. A plasmid DNA vaccine and a single-shot recombinant rhesus adenovirus serotype 52 vector vaccine, both expressing ZIKV premembrane and envelope, also elicited neutralizing antibodies and completely protected monkeys against ZIKV challenge. These data support the rapid clinical development of ZIKV vaccines for humans.

  3. Pre-Ebola virus disease laboratory system and related challenges in Liberia

    Directory of Open Access Journals (Sweden)

    Stephen B. Kennedy

    2016-10-01

    Full Text Available Prior to the Ebola virus disease outbreak in Liberia, the laboratory system was duplicativefragmented and minimally coordinated. The National Reference Laboratory was conceptualisedto address the existing challenges by promoting the implementation of effective and sustainablelaboratory services in Liberia. However, in a resource-limited environment such as Liberiaprogress regarding the rebuilding of the health system can be relatively slow, while efforts tosustain the transient gains remain a key challenge for the Ministry of Health. In this paper, wedescribe the pre-Ebola virus disease laboratory system in Liberia and its prevailing efforts toaddress future emerging infectious diseases, as well as current Infectious diseases, all of whichare exacerbated by poverty. We conclude that laboratory and diagnostic services in Liberiahave encountered numerous challenges regarding its efforts to strengthen the healthcaredelivery system. These challenges include limited trained human resource capacity, inadequateinfrastructure, and a lack of coordination. As with most countries in sub-Saharan Africa, whencomparing urban and rural settings, diagnostic and clinical services are generally skewedtoward urban health facilities and private, faith-based health facilities. We recommend thatstructured policy be directed at these challenges for national institutions to develop guidelinesto improve, strengthen and sustain diagnostic and curative laboratory services to effectivelyaddress current infectious diseases and prepare for future emerging and re-emerging infectiousdiseases.

  4. The VG/GA strain of Newcastle disease virus: Mucosal immunity, protection against lethal challenge and molecular analysis

    Science.gov (United States)

    The VG/GA strain of Newcastle disease virus (NDV) isolated from the intestine of healthy turkeys has been proposed to replicate in the respiratory and intestinal tract of chickens. In this study, the virus distribution, the mucosal and systemic immune response, the efficacy against lethal challenge...

  5. Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges.

    Science.gov (United States)

    Grant-Klein, Rebecca J; Altamura, Louis A; Badger, Catherine V; Bounds, Callie E; Van Deusen, Nicole M; Kwilas, Steven A; Vu, Hong A; Warfield, Kelly L; Hooper, Jay W; Hannaman, Drew; Dupuy, Lesley C; Schmaljohn, Connie S

    2015-01-01

    Cynomolgus macaques were vaccinated by intramuscular electroporation with DNA plasmids expressing codon-optimized glycoprotein (GP) genes of Ebola virus (EBOV) or Marburg virus (MARV) or a combination of codon-optimized GP DNA vaccines for EBOV, MARV, Sudan virus and Ravn virus. When measured by ELISA, the individual vaccines elicited slightly higher IgG responses to EBOV or MARV than did the combination vaccines. No significant differences in immune responses of macaques given the individual or combination vaccines were measured by pseudovirion neutralization or IFN-γ ELISpot assays. Both the MARV and mixed vaccines were able to protect macaques from lethal MARV challenge (5/6 vs. 6/6). In contrast, a greater proportion of macaques vaccinated with the EBOV vaccine survived lethal EBOV challenge in comparison to those that received the mixed vaccine (5/6 vs. 1/6). EBOV challenge survivors had significantly higher pre-challenge neutralizing antibody titers than those that succumbed.

  6. BacMam immunization partially protects pigs against sublethal challenge with African swine fever virus.

    Science.gov (United States)

    Argilaguet, Jordi M; Pérez-Martín, Eva; López, Sergio; Goethe, Martin; Escribano, J M; Giesow, Katrin; Keil, Günther M; Rodríguez, Fernando

    2013-04-01

    Lack of vaccines and efficient control measures complicate the control and eradication of African swine fever (ASF). Limitations of conventional inactivated and attenuated virus-based vaccines against African swine fever virus (ASFV) highlight the need to use new technologies to develop efficient and safe vaccines against this virus. With this aim in mind, in this study we have constructed BacMam-sHAPQ, a baculovirus based vector for gene transfer into mammalian cells, expressing a fusion protein comprising three in tandem ASFV antigens: p54, p30 and the extracellular domain of the viral hemagglutinin (secretory hemagglutinin, sHA), under the control of the human cytomegalovirus immediate early promoter (CMVie). Confirming its correct in vitro expression, BacMam-sHAPQ induced specific T-cell responses directly after in vivo immunization. Conversely, no specific antibody responses were detectable prior to ASFV challenge. The protective potential of this recombinant vaccine candidate was tested by a homologous sublethal challenge with ASFV following immunization. Four out of six immunized pigs remained viremia-free after ASFV infection, while the other two pigs showed similar viremic titres to control animals. The protection afforded correlated with the presence of a large number of virus-specific IFNγ-secreting T-cells in blood at 17 days post-infection. In contrast, the specific antibody levels observed after ASFV challenge in sera from BacMam-sHAPQ immunized pigs were indistinguishable from those found in control pigs. These results highlight the importance of the cellular responses in protection against ASFV and point towards BacMam vectors as potential tools for future vaccine development.

  7. Oral Immunization with Recombinant Vaccinia Virus Prime and Intramuscular Protein Boost Provides Protection against Intrarectal Simian-Human Immunodeficiency Virus Challenge in Macaques.

    Science.gov (United States)

    Thippeshappa, Rajesh; Tian, Baoping; Cleveland, Brad; Guo, Wenjin; Polacino, Patricia; Hu, Shiu-Lok

    2015-12-30

    Human immunodeficiency virus type 1 (HIV-1) acquisition occurs predominantly through mucosal transmission. We hypothesized that greater mucosal immune responses and protective efficacy against mucosal HIV-1 infection may be achieved by prime-boost immunization at mucosal sites. We used a macaque model to determine the safety, immunogenicity, and protective efficacy of orally delivered, replication-competent but attenuated recombinant vaccinia viruses expressing full-length HIV-1 SF162 envelope (Env) or simian immunodeficiency virus (SIV) Gag-Pol proteins. We examined the dose and route that are suitable for oral immunization with recombinant vaccinia viruses. We showed that sublingual inoculation of two vaccinia virus-naive pigtailed macaques with 5 × 10(8) PFU of recombinant vaccinia viruses was safe. However, sublingual inoculation with a higher dose or tonsillar inoculation resulted in secondary oral lesions, indicating the need to optimize the dose and route for oral immunization with replication-competent vaccinia virus vectors. Oral priming alone elicited antibody responses to vaccinia virus and to the SF162 Env protein. Intramuscular immunization with the SF162 gp120 protein at either 20 or 21 weeks postpriming resulted in a significant boost in antibody responses in both systemic and mucosal compartments. Furthermore, we showed that immune responses induced by recombinant vaccinia virus priming and intramuscular protein boosting provided protection against intrarectal challenge with the simian-human immunodeficiency virus SHIV-SF162-P4.

  8. Lung Irradiation Increases Mortality After Influenza A Virus Challenge Occurring Late After Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Manning, Casey M. [Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York (United States); Johnston, Carl J. [Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York (United States); Department of Pediatrics, University of Rochester Medical Center, Rochester, New York (United States); Reed, Christina K. [Department of Pediatrics, University of Rochester Medical Center, Rochester, New York (United States); Lawrence, B. Paige [Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York (United States); Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York (United States); Williams, Jacqueline P. [Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York (United States); Finkelstein, Jacob N., E-mail: Jacob_Finkelstein@urmc.rochester.edu [Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York (United States); Department of Pediatrics, University of Rochester Medical Center, Rochester, New York (United States); Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York (United States)

    2013-05-01

    Purpose: To address whether irradiation-induced changes in the lung environment alter responses to a viral challenge delivered late after exposure but before the appearance of late lung radiation injury. Methods and Materials: C57BL/6J mice received either lung alone or combined lung and whole-body irradiation (0-15 Gy). At 10 weeks after irradiation, animals were infected with 120 HAU influenza virus strain A/HKx31. Innate and adaptive immune cell recruitment was determined using flow cytometry. Cytokine and chemokine production and protein leakage into the lung after infection were assessed. Results: Prior irradiation led to a dose-dependent failure to regain body weight after infection and exacerbated mortality, but it did not affect virus-specific immune responses or virus clearance. Surviving irradiated animals displayed a persistent increase in total protein in bronchoalveolar lavage fluid and edema. Conclusions: Lung irradiation increased susceptibility to death after infection with influenza virus and impaired the ability to complete recovery. This altered response does not seem to be due to a radiation effect on the immune response, but it may possibly be an effect on epithelial repair.

  9. Addressing the Challenges of Hepatitis C Virus Resistance and Treatment Failure

    Directory of Open Access Journals (Sweden)

    Che C. Colpitts

    2016-08-01

    Full Text Available Chronic hepatitis C is a major cause of chronic liver disease, including liver cirrhosis and hepatocellular carcinoma. The development of direct-acting antivirals (DAAs revolutionized hepatitis C virus (HCV treatment by offering genuine prospects for the first comprehensive cure of a chronic viral infection in humans. While antiviral resistance is a significant limitation for interferon-based therapies, resistance and treatment failure still appear to be present in a small fraction of patients even in state-of-the-art DAA combination therapies. Therefore, treatment failure and resistance still remain a clinical challenge for the management of patients not responding to DAAs. In this special issue of Viruses on HCV drug resistance, mechanisms of antiviral resistance for different classes of antiviral drugs are described. Furthermore, the detection and monitoring of resistance in clinical practice, the clinical impact of resistance in different patient groups and strategies to prevent and address resistance and treatment failure using complementary antiviral strategies are reviewed.

  10. Neutrophils recruited to sites of infection protect from virus challenge by releasing neutrophil extracellular traps.

    Science.gov (United States)

    Jenne, Craig N; Wong, Connie H Y; Zemp, Franz J; McDonald, Braedon; Rahman, Masmudur M; Forsyth, Peter A; McFadden, Grant; Kubes, Paul

    2013-02-13

    Neutrophils mediate bacterial clearance through various mechanisms, including the release of mesh-like DNA structures or neutrophil extracellular traps (NETs) that capture bacteria. Although neutrophils are also recruited to sites of viral infection, their role in antiviral innate immunity is less clear. We show that systemic administration of virus analogs or poxvirus infection induces neutrophil recruitment to the liver microvasculature and the release of NETs that protect host cells from virus infection. After systemic intravenous poxvirus challenge, mice exhibit thrombocytopenia and the recruitment of both neutrophils and platelets to the liver vasculature. Circulating platelets interact with, roll along, and adhere to the surface of adherent neutrophils, forming large, dynamic aggregates. These interactions facilitate the release of NETs within the liver vasculature that are able to protect host cells from poxvirus infection. These findings highlight the role of NETs and early tissue-wide responses in preventing viral infection.

  11. Addressing the Challenges of Hepatitis C Virus Resistance and Treatment Failure.

    Science.gov (United States)

    Colpitts, Che C; Baumert, Thomas F

    2016-08-16

    Chronic hepatitis C is a major cause of chronic liver disease, including liver cirrhosis and hepatocellular carcinoma. The development of direct-acting antivirals (DAAs) revolutionized hepatitis C virus (HCV) treatment by offering genuine prospects for the first comprehensive cure of a chronic viral infection in humans. While antiviral resistance is a significant limitation for interferon-based therapies, resistance and treatment failure still appear to be present in a small fraction of patients even in state-of-the-art DAA combination therapies. Therefore, treatment failure and resistance still remain a clinical challenge for the management of patients not responding to DAAs. In this special issue of Viruses on HCV drug resistance, mechanisms of antiviral resistance for different classes of antiviral drugs are described. Furthermore, the detection and monitoring of resistance in clinical practice, the clinical impact of resistance in different patient groups and strategies to prevent and address resistance and treatment failure using complementary antiviral strategies are reviewed.

  12. Single-dose immunization with virus replicon particles confers rapid robust protection against Rift Valley fever virus challenge.

    Science.gov (United States)

    Dodd, Kimberly A; Bird, Brian H; Metcalfe, Maureen G; Nichol, Stuart T; Albariño, César G

    2012-04-01

    Rift Valley fever virus (RVFV) causes outbreaks of severe disease in people and livestock throughout Africa and the Arabian Peninsula. The potential for RVFV introduction outside the area of endemicity highlights the need for fast-acting, safe, and efficacious vaccines. Here, we demonstrate a robust system for the reverse genetics generation of a RVF virus replicon particle (VRP(RVF)) vaccine candidate. Using a mouse model, we show that VRP(RVF) immunization provides the optimal balance of safety and single-dose robust efficacy. VRP(RVF) can actively synthesize viral RNA and proteins but lacks structural glycoprotein genes, preventing spread within immunized individuals and reducing the risk of vaccine-induced pathogenicity. VRP(RVF) proved to be completely safe following intracranial inoculation of suckling mice, a stringent test of vaccine safety. Single-dose subcutaneous immunization with VRP(RVF), although it is highly attenuated, completely protected mice against a virulent RVFV challenge dose which was 100,000-fold greater than the 50% lethal dose (LD(50)). Robust protection from lethal challenge was observed by 24 h postvaccination, with 100% protection induced in as little as 96 h. We show that a single subcutaneous VRP(RVF) immunization initiated a systemic antiviral state followed by an enhanced adaptive response. These data contrast sharply with the much-reduced survivability and immune responses observed among animals immunized with nonreplicating viral particles, indicating that replication, even if confined to the initially infected cells, contributes substantially to protective efficacy at early and late time points postimmunization. These data demonstrate that replicon vaccines successfully bridge the gap between safety and efficacy and provide insights into the kinetics of antiviral protection from RVFV infection.

  13. Toll receptor response to white spot syndrome virus challenge in giant freshwater prawns (Macrobrachium rosenbergii).

    Science.gov (United States)

    Feng, Jinling; Zhao, Lingling; Jin, Min; Li, Tingting; Wu, Lei; Chen, Yihong; Ren, Qian

    2016-10-01

    Toll receptors are evolutionary ancient families of pattern recognition receptors with crucial roles in invertebrate innate immune response. In this study, we identified a Toll receptor (MrToll) from giant freshwater prawns (Macrobrachium rosenbergii). The full-length cDNA of MrToll is 4257 bp, which encodes a putative protein of 1367 amino acids. MrToll contains 17 LRR domains, a transmembrane domain, and a TIR domain. Phylogenetic analysis showed that MrToll was grouped with Drosophila Toll7 and other arthropod Tolls. The transcripts of MrToll are mainly distributed in the heart, hepatopancreas, gills, stomach, and intestine. A low level of MrToll expression can be detected in hemocytes and the lymphoid organ. MrToll expression in gills was gradually upregulated to the highest level from 24 h to 48 h during the white spot syndrome virus (WSSV) challenge. The expression levels of the crustin (Cru) genes Cru3 and Cru7 in gills were relatively lower than those of Cru2 and Cru4. The expression levels of Cru3 and Cru7 were inhibited after the RNA interference of MrToll in gills during the WSSV challenge. The anti-lipopolysaccharide factor (ALF) genes ALF2, ALF3, ALF4, and ALF5 were also regulated by MrToll in gills during the virus challenge. These findings suggest that MrToll may contribute to the innate immune defense of M. rosenbergii against WSSV.

  14. Deletion of virulence associated genes from attenuated African swine fever virus isolate OUR T88/3 decreases its ability to protect against challenge with virulent virus

    OpenAIRE

    Abrams, Charles C.; Goatley, Lynnette; Fishbourne, Emma; CHAPMAN, DAVID; Cooke, Lyndsay; Oura, Christopher A.; Netherton, Christopher L.; Takamatsu, Haru-Hisa; Dixon, Linda K.

    2013-01-01

    African swine fever virus (ASFV) causes an acute haemorrhagic disease of domestic pigs against which there is no effective vaccine. The attenuated ASFV strain OUR T88/3 has been shown previously to protect vaccinated pigs against challenge with some virulent strains including OUR T88/1. Two genes, DP71L and DP96R were deleted from the OUR T88/3 genome to create recombinant virus OUR T88/3ΔDP2. Deletion of these genes from virulent viruses has previously been shown to reduce ASFV virulence in ...

  15. Effect of phylogenetic diversity of velogenic Newcastle disease virus challenge on virus shedding post homologous and heterologous DNA vaccination in chickens.

    Science.gov (United States)

    Mohamed, Mahmoud H A; Abdelaziz, Adel M; Kumar, Sachin; Al-Habib, Malik A; Megahed, Mohamed M

    2016-01-01

    Newcastle disease (ND) is a highly devastating disease for the poultry industry as it causes high economic losses. In this present study, a DNA vaccine containing the F and HN surface antigens of a highly virulent Newcastle disease virus (NDV), NDV/1/Chicken/2005 (FJ939313), was successfully generated. Cell transfection test indicated that the vaccine expressed the F and HN genes in Hep-2 cells. The main objective of this study was to compare the extent of protection induced by DNA vaccination after homologous and heterologous NDV-challenge as determined by the amount of NDV shedding after challenge. NDV-antibody-negative chickens were vaccinated either once, twice or thrice intramuscularly at 7, 14 and 21 days old and were challenged 14 days post vaccination with either homologous virus (vaccine-matched velogenic viscerotropic Newcastle disease virus (vvNDV) strain, FJ939313), phylogenetically related to group VII, or a phylogenetically divergent heterologous virus (unmatched vvNDV strain, AY968809), which belongs to genogroup VI and shows 84.1% nucleotide similarity to the NDV-sequences of the DNA vaccine. Our data indicate that birds, which received a single dose of the DNA vaccine were poorly protected, and only 30-40% of these birds survived after challenge with high virus shedding titre. Multiple administration of the DNA vaccine induced high protection rates of 70-90% with reduced virus shedding compared to the non-vaccinated and challenged birds. Generally, homologous challenge led to reduced tracheal and cloacal shedding compared to the heterologous vvNDV strain. This study provides a promising approach for the control of ND in chickens using DNA vaccines, which are phylogenetically closely related to the circulating field strains.

  16. HoBi-Like Virus RNA Detected in Foetuses Following Challenge of Pregnant Cows that had Previously Given Birth to Calves Persistently Infected with Bovine Viral Diarrhoea Virus.

    Science.gov (United States)

    Bauermann, F V; Falkenberg, S M; Ridpath, J F

    2016-09-11

    The ability of ruminant pestivirus including bovine viral diarrhoea virus (BVDV) and the related emerging pestivirus, HoBi-like virus, to establish persistent infection (PI) following foetal infection is central to keeping these viruses in circulation. Non-PI dams carrying BVDV PI calves develop high levels of immunity due constantly viral exposure. A study to determine whether the immunity developed following the generation of a BVDV PI is enough to prevent HoBi-like virus infection of a subsequent foetus was performed. This study consisted of nine pregnant cows, four had birthed BVDV-1 PI calves in a previous pregnancy, three cows had birthed BVDV-2 PIs and two had birthed pestivirus negative calves. From this, six pregnant cows were challenged with HoBi-like virus about day 85 of gestation (four BVDV-1 and two BVDV-2 cows) and three non-challenged cows (negative control). At the day of challenge, the serum neutralizing titres against the homologous BVDV strains of the first inoculation ranged from 1148 to 5793. At day 6 post-challenge, HoBi-like RNA was detected in the serum of all four BVDV-1 cows but not in the two BVDV-2 cows. The foetuses harvested from five of the exposed dams (three BVDV-1 and two BVDV-2 cows) at day 30 post-challenge were positive for HoBi-like virus RNA. The sixth cow, BVDV-1 cow #541, while pregnant at the time of exposure, had no foetus 30 days after exposure. Foetuses from HoBi-like virus exposed dams were significantly smaller and lighter than control foetuses. HoBi-like RNA was detected in samples of all challenged foetuses. The identification of viral RNA in the serum of 4 cows at day 6 post-challenge, as well viral RNA detection in all foetuses 30 days post-inoculation, indicates that the foetuses of dams with high antibodies titres against BVDV-1 or BVDV-2 would not be protected from challenge with a HoBi-like virus.

  17. Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Aerosolized Monkeypox Virus

    Science.gov (United States)

    2010-09-01

    appearance of very few pox lesions and the appearance of observable clinical disease of short duration just prior to death. Finally, perhaps because of...the small size of the marmosets, blood was not drawn with great frequency and serum chemistries and CBCs were not performed, thus leaving many

  18. 42 CFR 71.56 - African rodents and other animals that may carry the monkeypox virus.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false African rodents and other animals that may carry... HUMAN SERVICES QUARANTINE, INSPECTION, LICENSING FOREIGN QUARANTINE Importations § 71.56 African rodents... import or attempt to import any rodents, whether dead or alive, that were obtained, directly...

  19. Newcastle disease virus (NDV) recombinants expressing infectious laryngotracheitis virus (ILTV) glycoproteins gB and gD protect chickens against ILTV and NDV challenges.

    Science.gov (United States)

    Zhao, Wei; Spatz, Stephen; Zhang, Zhenyu; Wen, Guoyuan; Garcia, Maricarmen; Zsak, Laszlo; Yu, Qingzhong

    2014-08-01

    Infectious laryngotracheitis (ILT) is a highly contagious acute respiratory disease of chickens caused by infectious laryngotracheitis virus (ILTV). The disease is controlled mainly through biosecurity and vaccination with live attenuated strains of ILTV and vectored vaccines based on turkey herpesvirus (HVT) and fowlpox virus (FPV). The current live attenuated vaccines (chicken embryo origin [CEO] and tissue culture origin [TCO]), although effective, can regain virulence, whereas HVT- and FPV-vectored ILTV vaccines are less efficacious than live attenuated vaccines. Therefore, there is a pressing need to develop safer and more efficacious ILTV vaccines. In the present study, we generated Newcastle disease virus (NDV) recombinants, based on the LaSota vaccine strain, expressing glycoproteins B (gB) and D (gD) of ILTV using reverse genetics technology. These recombinant viruses, rLS/ILTV-gB and rLS/ILTV-gD, were slightly attenuated in vivo yet retained growth dynamics, stability, and virus titers in vitro that were similar to those of the parental LaSota virus. Expression of ILTV gB and gD proteins in the recombinant virus-infected cells was detected by immunofluorescence assay. Vaccination of specific-pathogen-free chickens with these recombinant viruses conferred significant protection against virulent ILTV and velogenic NDV challenges. Immunization of commercial broilers with rLS/ILTV-gB provided a level of protection against clinical disease similar to that provided by the live attenuated commercial vaccines, with no decrease in body weight gains. The results of the study suggested that the rLS/ILTV-gB and -gD viruses are safe, stable, and effective bivalent vaccines that can be mass administered via aerosol or drinking water to large chicken populations. This paper describes the development and evaluation of novel bivalent vaccines against chicken infectious laryngotracheitis (ILT) and Newcastle disease (ND), two of the most economically important infectious

  20. Vaccination of horses with a recombinant modified vaccinia Ankara virus (MVA) expressing African horse sickness (AHS) virus major capsid protein VP2 provides complete clinical protection against challenge.

    Science.gov (United States)

    Alberca, Berta; Bachanek-Bankowska, Katarzyna; Cabana, Marta; Calvo-Pinilla, Eva; Viaplana, Elisenda; Frost, Lorraine; Gubbins, Simon; Urniza, Alicia; Mertens, Peter; Castillo-Olivares, Javier

    2014-06-17

    African horse sickness virus (AHSV) is an arthropod-borne pathogen that infects all species of equidae and causes high mortality in horses. Previously, a recombinant modified vaccinia Ankara (MVA) virus expressing the protein VP2 of AHSV serotype 4 was shown to induce virus neutralising antibodies in horses and protected interferon alpha receptor gene knock-out mice (IFNAR -/-) against virulent AHSV challenge. This study builds on the previous work, examining the protective efficacy of MVA-VP2 vaccination in the natural host of AHSV infection. A study group of 4 horses was vaccinated twice with a recombinant MVA virus expressing the major capsid protein (VP2) of AHSV serotype 9. Vaccinated animals and a control group of unvaccinated horses were then challenged with a virulent strain of AHSV-9. The vaccinated animals were completely protected against clinical disease and also against viraemia as measured by standard end-point dilution assays. In contrast, all control horses presented viraemia after challenge and succumbed to the infection. These results demonstrate the potential of recombinant MVA viruses expressing the outer capsid VP2 of AHSV as a protective vaccine against AHSV infection in the field.

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

    Science.gov (United States)

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

    2013-05-01

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

  2. A recombinant measles vaccine expressing chikungunya virus-like particles is strongly immunogenic and protects mice from lethal challenge with chikungunya virus.

    Science.gov (United States)

    Brandler, Samantha; Ruffié, Claude; Combredet, Chantal; Brault, Jean-Baptiste; Najburg, Valérie; Prevost, Marie-Christine; Habel, André; Tauber, Erich; Desprès, Philippe; Tangy, Frédéric

    2013-08-12

    Chikungunya virus (CHIKV), a mosquito-transmitted alphavirus, recently reemerged in the Indian Ocean, India and Southeast Asia, causing millions of cases of severe polyarthralgia. No specific treatment to prevent disease or vaccine to limit epidemics is currently available. Here we describe a recombinant live-attenuated measles vaccine (MV) expressing CHIKV virus-like particles comprising capsid and envelope structural proteins from the recent CHIKV strain La Reunion. Immunization of mice susceptible to measles virus induced high titers of CHIKV antibodies that neutralized several primary isolates. Specific cellular immune responses were also elicited. A single immunization with this vaccine candidate protected all mice from a lethal CHIKV challenge, and passive transfer of immune sera conferred protection to naïve mice. Measles vaccine is one of the safest and most effective human vaccines. A recombinant MV-CHIKV virus could make a safe and effective vaccine against chikungunya that deserves to be further tested in human trials.

  3. A recombinant vesicular stomatitis virus-based Lassa fever vaccine protects guinea pigs and macaques against challenge with geographically and genetically distinct Lassa viruses.

    Directory of Open Access Journals (Sweden)

    David Safronetz

    2015-04-01

    Full Text Available Lassa virus (LASV is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a "universal" LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models.Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever.Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever.

  4. Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge.

    Directory of Open Access Journals (Sweden)

    Petra van den Doel

    2014-09-01

    Full Text Available Chikungunya virus (CHIKV infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been documented, although at low incidences. The CHIKV RNA genome encodes five structural proteins (C, E1, E2, E3 and 6K. The E1 spike protein drives the fusion process within the cytoplasm, while the E2 protein is believed to interact with cellular receptors and therefore most probably constitutes the target of neutralizing antibodies. We have constructed recombinant Modified Vaccinia Ankara (MVA expressing E3E2, 6KE1, or the entire CHIKV envelope polyprotein cassette E3E26KE1. MVA is an appropriate platform because of its demonstrated clinical safety and its suitability for expression of various heterologous proteins. After completing the immunization scheme, animals were challenged with CHIV-S27. Immunization of AG129 mice with MVAs expressing E2 or E3E26KE1 elicited neutralizing antibodies in all animals and provided 100% protection against lethal disease. In contrast, 75% of the animals immunized with 6KE1 were protected against lethal infection. In conclusion, MVA expressing the glycoprotein E2 of CHIKV represents as an immunogenic and effective candidate vaccine against CHIKV infections.

  5. Susceptibility of goldsinny wrasse, Ctenolabrus rupestris L. (Labridae), to viral haemorrhagic septicaemia virus (VHSV) genotype III: Experimental challenge and pathology.

    Science.gov (United States)

    Matejusova, I; Noguera, P A; Hall, M; McBeath, A J A; Urquhart, K; Simons, J; Fordyce, M J; Lester, K; Ho, Y-M; Murray, W; Bruno, D W

    2016-04-15

    Cleaner fish, such as wrasse, are being increasingly used to combat the sea lice infestation of Atlantic salmon (Salmo salar L.) in many European countries. To determine susceptibility of the goldsinny wrasse (Ctenolabrus rupestris L.) and pathogenesis of the viral haemorrhagic septicaemia virus (VHSV) genotype III isolate 12-654, previously associated with VHSV infection in the Shetland Islands in 2012, fish were experimentally challenged by intraperitoneal injection (IP), bath immersion and cohabitation routes. Cumulative proportion of moribund wrasse reached 17% following the virus immersion challenge while by the IP-route moribunds exceeded 50% within 14days post-challenge. Typical signs of VHS as reported in rainbow trout (Oncorhynchus mykiss), were not observed in moribund goldsinny wrasse. The most pronounced histopathological changes, consistent regardless of the route of infection, were observed within the heart and included atrium myofibril degeneration, focal infiltration and multifocal necrosis, with prominent swelling of the endocardium and occasional detachment. Pathological changes in the atrium were associated with presence of the viral antigen as confirmed by a positive immunohistochemical staining. Virus clearance and heart tissue recovery were noted although further experiments are required to confirm these observations. The results of a cohabitation experiment confirmed that goldsinny wrasse shed viable virus and therefore represent a risk of virus transmission to other VHSV susceptible species. Similarities between the pathology in goldsinny wrasse induced through the controlled experimental challenges and that of wrasse spp. from an infection occurrence in Shetland are discussed.

  6. Intranasal immunisation with recombinant adenovirus vaccines protects against a lethal challenge with pneumonia virus of mice.

    Science.gov (United States)

    Maunder, Helen E; Taylor, Geraldine; Leppard, Keith N; Easton, Andrew J

    2015-11-27

    Pneumonia virus of mice (PVM) infection of BALB/c mice induces bronchiolitis leading to a fatal pneumonia in a dose-dependent manner, closely paralleling the development of severe disease during human respiratory syncytial virus infection in man, and is thus a recognised model in which to study the pathogenesis of pneumoviruses. This model system was used to investigate delivery of the internal structural proteins of PVM as a potential vaccination strategy to protect against pneumovirus disease. Replication-deficient recombinant human adenovirus serotype 5 (rAd5) vectors were constructed that expressed the M or N gene of PVM pathogenic strain J3666. Intranasal delivery of these rAd5 vectors gave protection against a lethal challenge dose of PVM in three different mouse strains, and protection lasted for at least 20 weeks post-immunisation. Whilst the PVM-specific antibody response in such animals was weak and inconsistent, rAd5N primed a strong PVM-specific CD8(+) T cell response and, to a lesser extent, a CD4(+) T cell response. These findings suggest that T-cell responses may be more important than serum IgG in the observed protection induced by rAd5N.

  7. Characterization of Immune Responses Induced by Ebola Virus Glycoprotein (GP) and Truncated GP Isoform DNA Vaccines and Protection Against Lethal Ebola Virus Challenge in Mice

    Science.gov (United States)

    Li, Wenfang; Ye, Ling; Carrion, Ricardo; Mohan, Gopi S.; Nunneley, Jerritt; Staples, Hilary; Ticer, Anysha; Patterson, Jean L.; Compans, Richard W.; Yang, Chinglai

    2015-01-01

    In addition to its surface glycoprotein (GP), Ebola virus directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. We recently reported that sGP actively diverts host antibody responses against the epitopes that it shares with GP and thereby allows itself to absorb anti-GP antibodies, a phenomenon we termed “antigenic subversion.” To investigate the effect of antigenic subversion by sGP on protection against virus infection, we compared immune responses induced by different prime-boost immunization regimens with GP and sGP DNA vaccines in mice and their efficacy against lethal Ebola virus challenge. Similar levels of anti-GP antibodies were induced by 2 immunizations with sGP and GP DNA vaccines. However, 2 immunizations with GP but not sGP DNA vaccine fully protected mice from lethal challenge. Boosting with sGP or GP DNA vaccine in mice that had been primed by GP or sGP DNA vaccine augmented the levels of anti-GP antibody responses and further improved protective efficacy against Ebola virus infection. These results show that both the quality and the levels of anti-GP antibody responses affect the efficacy of protection against Ebola virus infection. PMID:25877553

  8. DNA vaccination partially protects against African swine fever virus lethal challenge in the absence of antibodies.

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    Jordi M Argilaguet

    Full Text Available The lack of available vaccines against African swine fever virus (ASFV means that the evaluation of new immunization strategies is required. Here we show that fusion of the extracellular domain of the ASFV Hemagglutinin (sHA to p54 and p30, two immunodominant structural viral antigens, exponentially improved both the humoral and the cellular responses induced in pigs after DNA immunization. However, immunization with the resulting plasmid (pCMV-sHAPQ did not confer protection against lethal challenge with the virulent E75 ASFV-strain. Due to the fact that CD8(+ T-cell responses are emerging as key components for ASFV protection, we designed a new plasmid construct, pCMV-UbsHAPQ, encoding the three viral determinants above mentioned (sHA, p54 and p30 fused to ubiquitin, aiming to improve Class I antigen presentation and to enhance the CTL responses induced. As expected, immunization with pCMV-UbsHAPQ induced specific T-cell responses in the absence of antibodies and, more important, protected a proportion of immunized-pigs from lethal challenge with ASFV. In contrast with control pigs, survivor animals showed a peak of CD8(+ T-cells at day 3 post-infection, coinciding with the absence of viremia at this time point. Finally, an in silico prediction of CTL peptides has allowed the identification of two SLA I-restricted 9-mer peptides within the hemagglutinin of the virus, capable of in vitro stimulating the specific secretion of IFNγ when using PBMCs from survivor pigs. Our results confirm the relevance of T-cell responses in protection against ASF and open new expectations for the future development of more efficient recombinant vaccines against this disease.

  9. DNA vaccination partially protects against African swine fever virus lethal challenge in the absence of antibodies.

    Science.gov (United States)

    Argilaguet, Jordi M; Pérez-Martín, Eva; Nofrarías, Miquel; Gallardo, Carmina; Accensi, Francesc; Lacasta, Anna; Mora, Mercedes; Ballester, Maria; Galindo-Cardiel, Ivan; López-Soria, Sergio; Escribano, José M; Reche, Pedro A; Rodríguez, Fernando

    2012-01-01

    The lack of available vaccines against African swine fever virus (ASFV) means that the evaluation of new immunization strategies is required. Here we show that fusion of the extracellular domain of the ASFV Hemagglutinin (sHA) to p54 and p30, two immunodominant structural viral antigens, exponentially improved both the humoral and the cellular responses induced in pigs after DNA immunization. However, immunization with the resulting plasmid (pCMV-sHAPQ) did not confer protection against lethal challenge with the virulent E75 ASFV-strain. Due to the fact that CD8(+) T-cell responses are emerging as key components for ASFV protection, we designed a new plasmid construct, pCMV-UbsHAPQ, encoding the three viral determinants above mentioned (sHA, p54 and p30) fused to ubiquitin, aiming to improve Class I antigen presentation and to enhance the CTL responses induced. As expected, immunization with pCMV-UbsHAPQ induced specific T-cell responses in the absence of antibodies and, more important, protected a proportion of immunized-pigs from lethal challenge with ASFV. In contrast with control pigs, survivor animals showed a peak of CD8(+) T-cells at day 3 post-infection, coinciding with the absence of viremia at this time point. Finally, an in silico prediction of CTL peptides has allowed the identification of two SLA I-restricted 9-mer peptides within the hemagglutinin of the virus, capable of in vitro stimulating the specific secretion of IFNγ when using PBMCs from survivor pigs. Our results confirm the relevance of T-cell responses in protection against ASF and open new expectations for the future development of more efficient recombinant vaccines against this disease.

  10. A heterologous DNA prime-Venezuelan equine encephalitis virus replicon particle boost dengue vaccine regimen affords complete protection from virus challenge in cynomolgus macaques.

    Science.gov (United States)

    Chen, Lan; Ewing, Dan; Subramanian, Hemavathy; Block, Karla; Rayner, Jonathan; Alterson, Kimberly D; Sedegah, Martha; Hayes, Curtis; Porter, Kevin; Raviprakash, Kanakatte

    2007-11-01

    A candidate vaccine (D1ME-VRP) expressing dengue virus type 1 premembrane and envelope proteins in a Venezuelan equine encephalitis (VEE) virus replicon particle (VRP) system was constructed and tested in conjunction with a plasmid DNA vaccine (D1ME-DNA) expressing identical dengue virus sequences. Cynomolgus macaques were vaccinated with three doses of DNA (DDD), three doses of VRP (VVV group), or a heterologous DNA prime-VRP boost regimen (DDV) using two doses of DNA vaccine and a third dose of VRP vaccine. Four weeks after the final immunization, the DDV group produced the highest dengue virus type 1-specific immunoglobulin G antibody responses and virus-neutralizing antibody titers. Moderate T-cell responses were demonstrated only in DDD- and DDV-vaccinated animals. When vaccinated animals were challenged with live virus, all vaccination regimens showed significant protection from viremia. DDV-immunized animals were completely protected from viremia (mean time of viremia = 0 days), whereas DDD- and VVV-vaccinated animals had mean times of viremia of 0.66 and 0.75 day, respectively, compared to 6.33 days for the control group of animals.

  11. Evaluation of the efficacy provided by a Recombinant Canarypox-Vectored Equine West Nile Virus vaccine against an experimental West Nile Virus intrathecal challenge in horses.

    Science.gov (United States)

    Siger, Leonardo; Bowen, Richard; Karaca, Kemal; Murray, Michael; Jagannatha, Shyla; Echols, Brandy; Nordgren, Robert; Minke, Jules M

    2006-01-01

    Efficacy of the Recombitek Equine West Nile Virus (WNV) vaccine was evaluated against a WNV intrathecal challenge model that results in WNV-induced clinical disease. Ten vaccinated (twice at days 0 and 35) and 10 control horses were challenged 2 weeks after administration of the second vaccine with a virulent WNV by intrathecal administration. After the challenge, eight of 10 controls developed clinical signs of encephalomyelitis whereas one vaccinate exhibited muscle fasciculation only once. Nine controls and one vaccinate developed a fever. Histopathology revealed mild to moderate nonsuppurative encephalitis in eight controls and one vaccinate. None of the vaccinates and all of the controls developed WNV viremia after challenge. All vaccinated horses developed antibodies to WNV after vaccination. These and results of previous studies demonstrate efficacy of the Recombitek WNV vaccine against WNV-induced clinical disease and natural challenge with WNV-infected mosquitoes.

  12. Successful vaccination strategies that protect aged mice from lethal challenge from influenza virus and heterologous severe acute respiratory syndrome coronavirus.

    Science.gov (United States)

    Sheahan, Timothy; Whitmore, Alan; Long, Kristin; Ferris, Martin; Rockx, Barry; Funkhouser, William; Donaldson, Eric; Gralinski, Lisa; Collier, Martha; Heise, Mark; Davis, Nancy; Johnston, Robert; Baric, Ralph S

    2011-01-01

    Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP(3014)) or wild-type VEE glycoproteins (VRP(3000)) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP(3000)-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP(3014)-based vaccines were not. The superior protection for the aged observed with VRP(3000)-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP(3000) vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP(3014) platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future.

  13. Efficacy of Recombinant Canine Distemper Virus Expressing Leishmania Antigen against Leishmania Challenge in Dogs.

    Directory of Open Access Journals (Sweden)

    Ryuichi Miura

    Full Text Available Canine distemper virus (CDV vaccination confers long-term protection against CDV reinfection. To investigate the utility of CDV as a polyvalent vaccine vector for Leishmania, we generated recombinant CDVs, based on an avirulent Yanaka strain, that expressed Leishmania antigens: LACK, TSA, or LmSTI1 (rCDV-LACK, rCDV-TSA, and rCDV-LmSTI1, respectively. Dogs immunized with rCDV-LACK were protected against challenge with lethal doses of virulent CDV, in the same way as the parental Yanaka strain. To evaluate the protective effects of the recombinant CDVs against cutaneous leishmaniasis in dogs, dogs were immunized with one recombinant CDV or a cocktail of three recombinant CDVs, before intradermal challenge (in the ears with infective-stage promastigotes of Leishmania major. Unvaccinated dogs showed increased nodules with ulcer formation after 3 weeks, whereas dogs immunized with rCDV-LACK showed markedly smaller nodules without ulceration. Although the rCDV-TSA- and rCDV-LmSTI1-immunized dogs showed little protection against L. major, the cocktail of three recombinant CDVs more effectively suppressed the progression of nodule formation than immunization with rCDV-LACK alone. These results indicate that recombinant CDV is suitable for use as a polyvalent live attenuated vaccine for protection against both CDV and L. major infections in dogs.

  14. Reverse osmosis integrity monitoring in water reuse: The challenge to verify virus removal - A review.

    Science.gov (United States)

    Pype, Marie-Laure; Lawrence, Michael G; Keller, Jurg; Gernjak, Wolfgang

    2016-07-01

    A reverse osmosis (RO) process is often included in the treatment train to produce high quality reuse water from treated effluent for potable purposes because of its high removal efficiency for salinity and many inorganic and organic contaminants, and importantly, it also provides an excellent barrier for pathogens. In order to ensure the continued protection of public health from pathogen contamination, monitoring RO process integrity is necessary. Due to their small sizes, viruses are the most difficult class of pathogens to be removed in physical separation processes and therefore often considered the most challenging pathogen to monitor. To-date, there is a gap between the current log credit assigned to this process (determined by integrity testing approved by regulators) and its actual log removal capability as proven in a variety of laboratory and pilot studies. Hence, there is a challenge to establish a methodology that more closely links to the theoretical performance. In this review, after introducing the notion of risk management in water reuse, we provide an overview of existing and potentially new RO integrity monitoring techniques, highlight their strengths and drawbacks, and debate their applicability to full-scale treatment plants, which open to future research opportunities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge

    Science.gov (United States)

    Bradley, Todd; Pollara, Justin; Santra, Sampa; Vandergrift, Nathan; Pittala, Srivamshi; Bailey-Kellogg, Chris; Shen, Xiaoying; Parks, Robert; Goodman, Derrick; Eaton, Amanda; Balachandran, Harikrishnan; Mach, Linh V.; Saunders, Kevin O.; Weiner, Joshua A.; Scearce, Richard; Sutherland, Laura L.; Phogat, Sanjay; Tartaglia, Jim; Reed, Steven G.; Hu, Shiu-Lok; Theis, James F.; Pinter, Abraham; Montefiori, David C.; Kepler, Thomas B.; Peachman, Kristina K.; Rao, Mangala; Michael, Nelson L.; Suscovich, Todd J.; Alter, Galit; Ackerman, Margaret E.; Moody, M. Anthony; Liao, Hua-Xin; Tomaras, Georgia; Ferrari, Guido; Korber, Bette T.; Haynes, Barton F.

    2017-01-01

    The RV144 Thai trial HIV-1 vaccine of recombinant poxvirus (ALVAC) and recombinant HIV-1 gp120 subtype B/subtype E (B/E) proteins demonstrated 31% vaccine efficacy. Here we design an ALVAC/Pentavalent B/E/E/E/E vaccine to increase the diversity of gp120 motifs in the immunogen to elicit a broader antibody response and enhance protection. We find that immunization of rhesus macaques with the pentavalent vaccine results in protection of 55% of pentavalent-vaccine-immunized macaques from simian–human immunodeficiency virus (SHIV) challenge. Systems serology of the antibody responses identifies plasma antibody binding to HIV-infected cells, peak ADCC antibody titres, NK cell-mediated ADCC and antibody-mediated activation of MIP-1β in NK cells as the four immunological parameters that best predict decreased infection risk that are improved by the pentavalent vaccine. Thus inclusion of additional gp120 immunogens to a pox-prime/protein boost regimen can augment antibody responses and enhance protection from a SHIV challenge in rhesus macaques. PMID:28593989

  16. Soluble F proteins exacerbate pulmonary histopathology after vaccination upon respiratory syncytial virus challenge but not when presented on virus-like particles.

    Science.gov (United States)

    Lee, Youri; Lee, Young-Tae; Ko, Eun-Ju; Kim, Ki-Hye; Hwang, Hye Suk; Park, Soojin; Kwon, Young-Man; Kang, Sang Moo

    2017-08-30

    Respiratory syncytial virus (RSV) fusion (F) protein is suggested to be a protective vaccine target although its efficacy and safety concerns remain not well understood. We investigated immunogenicity, efficacy, and safety of F proteins in a soluble form or on virus-like particle (F-VLP). F VLP preferentially elicited IgG2a antibody and T helper type 1 (Th1) immune responses whereas F protein induced IgG1 isotype and Th2 responses. Despite lung viral clearance after prime or prime-boost and then RSV challenge, F protein immune mice displayed weight loss and lung histopathology and high mucus production and eosinophils. In contrast, prime or prime-boost vaccination of F VLP induced effective protection, prevented infiltration of eosinophils, and vaccine- enhanced disease after challenge. This study provides insight into developing an effective and safe RSV vaccine candidate.

  17. A transcriptome study on Macrobrachium rosenbergii hepatopancreas experimentally challenged with white spot syndrome virus (WSSV).

    Science.gov (United States)

    Rao, Rama; Bhassu, Subha; Bing, Robin Zhu Ya; Alinejad, Tahereh; Hassan, Sharifah Syed; Wang, Jun

    2016-05-01

    The world production of shrimp such as the Malaysian giant freshwater prawn, Macrobrachium rosenbergii is seriously affected by the white spot syndrome virus (WSSV). There is an urgent need to understand the host pathogen interaction between M. rosenbergii and WSSV which will be able to provide a solution in controlling the spread of this infectious disease and lastly save the aquaculture industry. Now, using Next Generation Sequencing (NGS), we will be able to capture the response of the M. rosenbergii to the pathogen and have a better understanding of the host defence mechanism. Two cDNA libraries, one of WSSV-challenged M. rosenbergii and a normal control one, were sequenced using the Illumina HiSeq™ 2000 platform. After de novo assembly and clustering of the unigenes from both libraries, 63,584 standard unigenes were generated with a mean size of 698bp and an N50 of 1137bp. We successfully annotated 35.31% of all unigenes by using BLASTX program (E-value <10-5) against NCBI non-redundant (Nr), Swiss-Prot, Kyoto Encyclopedia of Genes and Genome pathway (KEGG) and Orthologous Groups of proteins (COG) databases. Gene Ontology (GO) assessment was conducted using BLAST2GO software. Differentially expressed genes (DEGs) by using the FPKM method showed 8443 host genes were significantly up-regulated whereas 5973 genes were significantly down-regulated. The differentially expressed immune related genes were grouped into 15 animal immune functions. The present study showed that WSSV infection has a significant impact on the transcriptome profile of M. rosenbergii's hepatopancreas, and further enhanced the knowledge of this host-virus interaction. Furthermore, the high number of transcripts generated in this study will provide a platform for future genomic research on freshwater prawns.

  18. Efficacy of vaccination for bluetongue virus serotype 8 performed shortly before challenge and implications for animal trade.

    Science.gov (United States)

    Spedicato, Massimo; Lorusso, Alessio; Salini, Romolo; Gennaro, Annapia Di; Leone, Alessandra; Teodori, Liana; Casaccia, Claudia; Portanti, Ottavio; Calistri, Paolo; Giovannini, Armando; Savini, Giovanni

    2017-01-01

    Vaccination is the most effective strategy for controlling Bluetongue virus (BTV) spread and economic consequences thereof. In this study we verified in sheep, using one commercially available inactivated vaccine for BTV-8 (BTVPUR AlSap 8), when, during the recommended vaccination schedule, animals start to be effectively protected against challenge with wild-type strain. To this aim, sheep were challenged at different time points shortly after the first vaccine injection. Twenty-four Sarda sheep were divided into four groups vaccinated two weeks before challenge (Group A), one week before challenge (Group B) and concurrently with challenge (Group C). A second vaccine was performed twenty-eight days later with respect the first vaccine administration in each experimental group. The last group consisted of six non vaccinated-infected animals (NVIA). Virological and serological examinations were performed before and after challenge up to 42 and 77days post challenge, respectively. The results of the study show that vaccination commenced as little as two weeks before challenge (Group A) prevented viremia and RNAemia in challenged sheep altogether. Conversely, Group B was partially protected from challenge and Group C showed viraemia and RNAemia similar to NVIA. This study indicates that the first administration of inactivated vaccine performed two weeks before challenge was able to prevent viraemia. Overall, our findings may have direct consequences for the management of an unexpected BTV-8 outbreak in sheep and for the legislation on sheep trade from BTV restriction areas.

  19. Recombinant infectious bronchitis virus (IBV) H120 vaccine strain expressing the hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) protects chickens against IBV and NDV challenge.

    Science.gov (United States)

    Yang, Xin; Zhou, Yingshun; Li, Jianan; Fu, Li; Ji, Gaosheng; Zeng, Fanya; Zhou, Long; Gao, Wenqian; Wang, Hongning

    2016-05-01

    Infectious bronchitis (IB) and Newcastle disease (ND) are common viral diseases of chickens, which are caused by infectious bronchitis virus (IBV) and Newcastle disease virus (NDV), respectively. Vaccination with live attenuated strains of IBV-H120 and NDV-LaSota are important for the control of IB and ND. However, conventional live attenuated vaccines are expensive and result in the inability to differentiate between infected and vaccinated chickens. Therefore, there is an urgent need to develop new efficacious vaccines. In this study, using a previously established reverse genetics system, we generated a recombinant IBV virus based on the IBV H120 vaccine strain expressing the haemagglutinin-neuraminidase (HN) protein of NDV. The recombinant virus, R-H120-HN/5a, exhibited growth dynamics, pathogenicity and viral titers that were similar to those of the parental IBV H120, but it had acquired hemagglutination activity from NDV. Vaccination of SPF chickens with the R-H120-HN/5a virus induced a humoral response at a level comparable to that of the LaSota/H120 commercial bivalent vaccine and provided significant protection against challenge with virulent IBV and NDV. In summary, the results of this study indicate that the IBV H120 strain could serve as an effective tool for designing vaccines against IB and other infectious diseases, and the generation of IBV R-H120-HN/5a provides a solid foundation for the development of an effective bivalent vaccine against IBV and NDV.

  20. Recent Perspectives on Genome, Transmission, Clinical Manifestation, Diagnosis, Therapeutic Strategies, Vaccine Developments, and Challenges of Zika Virus Research

    Directory of Open Access Journals (Sweden)

    Apoorva Shankar

    2017-09-01

    Full Text Available One of the potential threats to public health microbiology in 21st century is the increased mortality rate caused by Zika virus (ZIKV, a mosquito-borne flavivirus. The severity of ZIKV infection urged World Health Organization (WHO to declare this virus as a global concern. The limited knowledge on the structure, virulent factors, and replication mechanism of the virus posed as hindrance for vaccine development. Several vector and non-vector-borne mode of transmission are observed for spreading the disease. The similarities of the virus with other flaviviruses such as dengue and West Nile virus are worrisome; hence, there is high scope to undertake ZIKV research that probably provide insight for novel therapeutic intervention. Thus, this review focuses on the recent aspect of ZIKV research which includes the outbreak, genome structure, multiplication and propagation of the virus, current animal models, clinical manifestations, available treatment options (probable vaccines and therapeutics, and the recent advancements in computational drug discovery pipelines, challenges and limitation to undertake ZIKV research. The review suggests that the infection due to ZIKV became one of the universal concerns and an interdisciplinary environment of in vitro cellular assays, genomics, proteomics, and computational biology approaches probably contribute insights for screening of novel molecular targets for drug design. The review tried to provide cutting edge knowledge in ZIKV research with future insights required for the development of novel therapeutic remedies to curtail ZIKV infection.

  1. To be or not to be alive: How recent discoveries challenge the traditional definitions of viruses and life.

    Science.gov (United States)

    Forterre, Patrick

    2016-10-01

    Three major discoveries have recently profoundly modified our perception of the viral world: molecular ecologists have shown that viral particles are more abundant than cells in natural environments; structural biologists have shown that some viruses from the three domains of life, Bacteria, Eukarya and Archaea, are evolutionarily related, and microbiologists have discovered giant viruses that rival with cells in terms of size and gene content. I discuss here the scientific and philosophical impact of these discoveries on the debates over the definition, nature (living or not), and origin of viruses. I suggest that viruses have often been considered non-living, because they are traditionally assimilated to their virions. However, the term virus describes a biological process and should integrate all aspects of the viral reproduction cycle. It is especially important to focus on the intracellular part of this cycle, the virocell, when viral information is actively expressed and reproduced, allowing the emergence of new viral genes. The virocell concept theoretically removes roadblocks that prevent defining viruses as living organisms. However, defining a "living organism" remains challenging, as indicated by the case of organelles that evolved from intracellular bacteria. To bypass this problem, I suggest considering that all biological entities that actively participate in the process of life are living.

  2. Could an experimental dengue virus infection fail to induce solid immunity against homologous viral challenge in non-human primates?

    Science.gov (United States)

    Valdés, Iris; Gil, Lázaro; Lazo, Laura; Marcos, Ernesto; Martín, Jorge; Suzarte, Edith; Castro, Jorge; Romero, Yaremis; Guillén, Gerardo; Hermida, Lisset

    2016-02-01

    There are several dengue vaccine candidates at advanced stages of development, but none of them are licensed. Despite the reactogenicity and immunogenicity profile in humans of the tetravalent ChimeriVax™ dengue vaccine candidate, in efficacy trials, it has failed to confer complete protection against dengue virus (DENV)-1 and DENV-2. However, full protection against the four serotypes had been observed previously in monkeys immunized with this vaccine candidate. Some authors have tried to explain this contradiction by hypothesizing that protection rates in non-human primates (NHPs) are associated with a lack of post-challenge anamnestic immune responses. Here, we studied the protection and anamnestic response patterns after homologous challenge in NHPs previously infected with DENV-2. Two immunization schemes were used, varying the viral doses and the intervals between them. Animals developed immunity against DENV-2 that provided full protection against reinfection with a homologous virus. However, all monkeys showed a significant increase in antiviral and neutralizing antibody titers after challenge. Our results suggest that sterilizing immunity could not be induced by infection with the virus despite the lack of detectable viremia in some animals in which an increase in antibody titer was observed. For this reason, we propose that the lack of an anamnestic neutralizing antibody response after challenge, as suggested by some authors, should be carefully reviewed as a criterion for evaluating the functionality of vaccine candidates.

  3. [Challenges of lopinavir/ritonavir in the chronicity of human immunodeficiency virus infection].

    Science.gov (United States)

    Aguirrebengoa, Koldo

    2014-11-01

    Combination antiretroviral therapy (ART) has increased patient survival, which is currently similar to that of the general population in western countries. However, ART is unable to completely restore normal health, given the persistence of chronic immune activation. Human immunodeficiency virus (HIV) infection has become a chronic disease and 50% of patients will soon be older than 50 years. Currently, there is a debate on the possibility of accelerated aging in the HIV-infected population. An overlap has been observed between chronic inflammation, age-related comorbidities, lifestyle, and the long-term toxicity of ART. ART-related toxicity can encourage the development of comorbidities, especially cardiovascular and renal complications, while toxicity-especially that of thymidine analogs-can also contribute to inflammation and aging. Evidence is available on simplification strategies with boosted protease inhibitor monotherapy aiming to avoid or reduce potential or demonstrated toxicity. Currently, studies are underway of dual therapy strategies with lopinavir/ritonavir (LPV/r) with distinct antiretroviral agents. The studies with the largest samples are those with raltegravir and lamivudine. The GARDEL trial has demonstrated that dual therapy with LPV/r plus a generic drug such as lamivudine is non-inferior to triple therapy in treatment- naïve patients. All of the above indicates the response to the challenge posed to LPV/r by the chronic phase of the disease and by the need to reduce costs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  4. Tuberculosis and human immunodeficiency virus co-infection in children: management challenges.

    Science.gov (United States)

    Chintu, Chifumbe

    2007-06-01

    The pattern of childhood human immunodeficiency virus (HIV) and tuberculosis (TB) infection mirror these epidemics in the adult population. The number of children co-infected with HIV and TB is rising, and the incidence of congenital and neonatal TB is similarly increasing. In addition, the emergence of multidrug resistant TB and extensively drug-resistant TB has occurred within the context of a high prevalence of HIV and TB. The diagnosis of TB has always been difficult in children and is compounded by HIV co-infection. The clinical symptoms in both diseases are similar, and the radiological changes may be non-specific. Treatment of both conditions in children is a challenge due to drug interactions and problems with adherence. In most developing countries, there are few medicines specifically tested and manufactured for children, with few stable syrup formulations. Thus antituberculosis and antiretroviral tablets have to be divided, giving rise to unpredictable dosing and the possible emergence of resistance. To reduce the morbidity and mortality of TB and HIV, existing childhood TB programmes must be strengthened, and antiretroviral drug therapy and mother-to-child transmission programmes scaled up. An increased emphasis on childhood TB, with early diagnosis and treatment, must be a priority. The provision of isoniazid prophylaxis to HIV-infected children exposed to an adult case of TB or, in areas with a high prevalence of TB, to HIV-infected children (irrespective of a TB contact) may be effective in reducing the morbidity and mortality from childhood TB.

  5. Myxomavirus as a vector for the immunisation of sheep: protection study against challenge with bluetongue virus.

    Science.gov (United States)

    Top, Sokunthea; Foucras, Gilles; Deplanche, Martine; Rives, Germain; Calvalido, Jérôme; Comtet, Loic; Bertagnoli, Stéphane; Meyer, Gilles

    2012-02-21

    Recombinant poxviruses are well suited for the development of new vaccine vectors. Our previous data supported the idea that Myxomavirus (MYXV) is efficient at priming antibody responses in sheep. To provide definitive evidence on the potential of MYXV for vaccination against infectious diseases in ruminants, we investigated the immune protection provided by recombinant MYXV against bluetongue, a devastating disease in sheep. To test this concept, sheep were injected twice with an MYXV expressing the immunodominant VP2 protein (SG33-VP2). The SG33-VP2 vector promoted the production of neutralising antibodies and partially protected sheep against disease after challenge with a highly virulent strain of serotype-8 bluetongue virus (BTV-8). In contrast, an MYXV expressing both VP2 and VP5 proteins (SG33-VP2/5) elicited very little protection. The expression levels of the VP2 and VP5 proteins suggested that, greater than the co-expression of the VP5 protein which was previously thought to favour anti-VP2 antibody response, the high expression of VP2 may be critical in the MYXV context to stimulate a protective response in sheep. This highlights the requirement for a careful examination of antigen expression before any conclusion can be drawn on the respective role of the protective antigens. As a proof of principle, our study shows that an MYXV vaccine vector is possible in ruminants.

  6. Gene Expression Profiling of Monkeypox Virus-Infected Cells Reveals Novel Interfaces for Host-Virus Interactions

    Science.gov (United States)

    2010-07-28

    and included metabolism of essential building blocks such as amino acids, lipids , and carbohydrates (Fig. 4B), and other functions related to cell...by RT PCR RT PCR was performed utilizing the Superarray human common cytokines panel ( PAHS -021E-4, Superarray, Frederick MD, 21703). Reactions were

  7. CNS recruitment of CD8+ T lymphocytes specific for a peripheral virus infection triggers neuropathogenesis during polymicrobial challenge.

    Directory of Open Access Journals (Sweden)

    Christine M Matullo

    2011-12-01

    Full Text Available Although viruses have been implicated in central nervous system (CNS diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with both CNS-restricted measles virus (MV and peripherally restricted lymphocytic choriomeningitis virus (LCMV. While infection with either virus alone resulted in no illness, infection with both viruses caused disease in all mice, with ∼50% dying following seizures. Co-infection resulted in a 12-fold increase in the number of CD8+ T cells in the brain as compared to MV infection alone. Tetramer analysis revealed that a substantial proportion (>35% of these infiltrating CD8+ lymphocytes were LCMV-specific, despite no detectable LCMV in CNS tissues. Mechanistically, CNS disease was due to edema, induced in a CD8-dependent but perforin-independent manner, and brain herniation, similar to that observed in mice challenged intracerebrally with LCMV. These results indicate that T cell trafficking can be influenced by other ongoing immune challenges, and that CD8+ T cell recruitment to the brain can trigger CNS disease in the apparent absence of cognate antigen. By extrapolation, human CNS diseases of unknown etiology need not be associated with infection with any particular agent; rather, a condition that compromises and activates the blood-brain barrier and adjacent brain parenchyma can render the CNS susceptible to pathogen-independent immune attack.

  8. A recombinant DNA vaccine protects mice deficient in the alpha/beta interferon receptor against lethal challenge with Usutu virus.

    Science.gov (United States)

    Martín-Acebes, Miguel A; Blázquez, Ana-Belén; Cañas-Arranz, Rodrigo; Vázquez-Calvo, Ángela; Merino-Ramos, Teresa; Escribano-Romero, Estela; Sobrino, Francisco; Saiz, Juan-Carlos

    2016-04-19

    Usutu virus (USUV) is a mosquito-borne flavivirus whose circulation had been confined to Africa since it was first detected in 1959. However, in the last decade USUV has emerged in Europe causing episodes of avian mortality and sporadic severe neuroinvasive infections in humans. Remarkably, adult laboratory mice exhibit limited susceptibility to USUV infection, which has impaired the analysis of the immune responses, thus complicating the evaluation of virus-host interactions and of vaccine candidates against this pathogen. In this work, we showed that mice deficient in the alpha/beta interferon receptor (IFNAR (-/-) mice) were highly susceptible to USUV infection and provided a lethal challenge model for vaccine testing. To validate this infection model, a plasmid DNA vaccine candidate encoding the precursor of membrane (prM) and envelope (E) proteins of USUV was engineered. Transfection of cultured cells with this plasmid resulted in expression of USUV antigens and the assembly and secretion of small virus-like particles also known as recombinant subviral particles (RSPs). A single intramuscular immunization with this plasmid was sufficient to elicit a significant level of protection against challenge with USUV in IFNAR (-/-) mice. The characterization of the humoral response induced revealed that DNA vaccination primed anti-USUV antibodies, including neutralizing antibodies. Overall, these results probe the suitability of IFNAR (-/-) mice as an amenable small animal model for the study of USUV host virus interactions and vaccine testing, as well as the feasibility of DNA-based vaccine strategies for the control of this pathogen.

  9. A multiagent filovirus DNA vaccine delivered by intramuscular electroporation completely protects mice from ebola and Marburg virus challenge.

    Science.gov (United States)

    Grant-Klein, Rebecca J; Van Deusen, Nicole M; Badger, Catherine V; Hannaman, Drew; Dupuy, Lesley C; Schmaljohn, Connie S

    2012-11-01

    We evaluated the immunogenicity and protective efficacy of DNA vaccines expressing the codon-optimized envelope glycoprotein genes of Zaire ebolavirus, Sudan ebolavirus, and Marburg marburgvirus (Musoke and Ravn). Intramuscular or intradermal delivery of the vaccines in BALB/c mice was performed using the TriGrid™ electroporation device. Mice that received DNA vaccines against the individual viruses developed robust glycoprotein-specific antibody titers as determined by ELISA and survived lethal viral challenge with no display of clinical signs of infection. Survival curve analysis revealed there was a statistically significant increase in survival compared to the control groups for both the Ebola and Ravn virus challenges. These data suggest that further analysis of the immune responses generated in the mice and additional protection studies in nonhuman primates are warranted.

  10. Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge

    NARCIS (Netherlands)

    Doel, van den P.; Volz, A.; Roose, J.M.; Sewbalaksing, V.D.; Pijlman, G.P.; Middelkoop, van I.; Duiverman, V.; Wetering, van de E.; Sutter, G.; Osterhaus, A.D.; Martina, B.E.

    2014-01-01

    Chikungunya virus (CHIKV) infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been docum

  11. Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges.

    Science.gov (United States)

    Delrue, Iris; Verzele, Dieter; Madder, Annemieke; Nauwynck, Hans J

    2012-06-01

    The aim of this review is to make researchers aware of the benefits of an efficient quality control system for prediction of a developed vaccine's efficacy. Two major goals should be addressed when inactivating a virus for vaccine purposes: first, the infectious virus should be inactivated completely in order to be safe, and second, the viral epitopes important for the induction of protective immunity should be conserved after inactivation in order to have an antigen of high quality. Therefore, some problems associated with the virus inactivation process, such as virus aggregate formation, protein crosslinking, protein denaturation and degradation should be addressed before testing an inactivated vaccine in vivo.

  12. Memory B cells and CD8⁺ lymphocytes do not control seasonal influenza A virus replication after homologous re-challenge of rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Timothy D Carroll

    Full Text Available This study sought to define the role of memory lymphocytes in the protection from homologous influenza A virus re-challenge in rhesus macaques. Depleting monoclonal antibodies (mAb were administered to the animals prior to their second experimental inoculation with a human seasonal influenza A virus strain. Treatment with either anti-CD8α or anti-CD20 mAbs prior to re-challenge had minimal effect on influenza A virus replication. Thus, in non-human primates with pre-existing anti-influenza A antibodies, memory B cells and CD8α⁺ T cells do not contribute to the control of virus replication after re-challenge with a homologous strain of influenza A virus.

  13. Cross-Protection against Challenge with Puumala Virus after Immunization with Nucleocapsid Proteins from Different Hantaviruses

    Science.gov (United States)

    de Carvalho Nicacio, Cristina; Gonzalez Della Valle, Marcelo; Padula, Paula; Björling, Ewa; Plyusnin, Alexander; Lundkvist, Åke

    2002-01-01

    Hantaviruses are rodent-borne agents that cause hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome in humans. The nucleocapsid protein (N) is relatively conserved among hantaviruses and highly immunogenic in both laboratory animals and humans, and it has been shown to induce efficient protective immunity in animal models. To investigate the ability of recombinant N (rN) from different hantaviruses to elicit cross-protection, we immunized bank voles with rN from Puumala (PUUV), Topografov (TOPV), Andes (ANDV), and Dobrava (DOBV) viruses and subsequently challenged them with PUUV. All animals immunized with PUUV and TOPV rN were completely protected. In the group immunized with DOBV rN, 7 of 10 animals were protected, while only 3 of 8 animals were protected in the group immunized with ANDV rN, which is more closely related to PUUV rN than DOBV rN. Humoral and cellular immune responses after rN immunization were also investigated. The highest cross-reactive humoral responses against PUUV antigen were detected in sera from ANDV rN-immunized animals, followed by those from TOPV rN-immunized animals, and only very low antibody cross-reactivity was observed in sera from DOBV rN-immunized animals. In proliferation assays, T lymphocytes from animals immunized with all heterologous rNs were as efficiently recalled in vitro by PUUV rN as were T lymphocytes from animals immunized with homologous protein. In summary, this study has shown that hantavirus N can elicit cross-protective immune responses against PUUV, and the results suggest a more important role for the cellular arm of the immune response than for the humoral arm in cross-protection elicited by rN. PMID:12050380

  14. Differential outcomes of Zika virus infection in Aedes aegypti orally challenged with infectious blood meals and infectious protein meals.

    Science.gov (United States)

    Huang, Yan-Jang S; Lyons, Amy C; Hsu, Wei-Wen; Park, So Lee; Higgs, Stephen; Vanlandingham, Dana L

    2017-01-01

    infection in mosquitoes. Infectious whole blood meals and infectious bovine serum albumin meals containing ZIKV were orally presented to two different groups of Ae. aegypti through membrane feeding. At 7 and 14 days post infection, infectious viruses were detected and viral dissemination from gut to other mosquito tissues was analyzed in orally challenged mosquitoes with 50% tissue culture infectious dose method on Vero76 cells. Zika virus infection was significantly impaired among mosquitoes orally challenged with infectious protein meals as compared to infectious whole blood meals. These results indicate the importance of the blood meal in the infection process of arboviruses in mosquitoes. It provides the basis for future studies to identify critical components in the blood of vertebrate hosts that facilitate arbovirus infection in mosquitoes.

  15. Emerging technologies for the detection of rabies virus: challenges and hopes in the 21st century.

    Directory of Open Access Journals (Sweden)

    Anthony R Fooks

    2009-09-01

    Full Text Available The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied. In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus. These tests enable viral strain identification from clinical specimens. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now. The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally. Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation. Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured. Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries. Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms. Antemortem

  16. Quantitative profiling of the shedding rate of the three Marek's disease virus (MDV) serotypes reveals that challenge with virulent MDV markedly increases shedding of vaccinal viruses.

    Science.gov (United States)

    Islam, Aminul; Walkden-Brown, Stephen W

    2007-08-01

    The shedding profile of Marek's disease virus serotype 1 (MDV1, virulent), serotype 2 (MDV2, vaccinal) and herpesvirus of turkeys (HVT, vaccinal) in commercial broiler chickens was determined by measuring the daily rate of production of feather dander from chickens housed in isolators and by quantifying the viral load of each of these serotypes in the dander using quantitative real-time PCR (qPCR). MDV1 and HVT viruses were detectable in dander filtered from isolator exhaust air from day 7 and MDV2 from day 12 after infection and thereafter until the end of the experiment at 61 days of age of the chickens. There was no difference in shedding rate among the three MDV1 isolates. Daily shedding of MDV1 increased sharply between days 7 and 28 and stabilized thereafter at about 10(9) virus copies per chicken per day, irrespective of vaccination status. Challenge with the three different MDV1 isolates markedly increased shedding of the vaccinal viruses HVT and MDV2 in dander by 38- and 75-fold, respectively. These results demonstrate the utility of qPCR for the differentiation and quantification of different MDV serotypes in feather dander and have significant implications for the routine monitoring of Marek's disease using qPCR assays of dust, for epidemiological modelling of the behaviour and spread of MDVs in chicken populations and for studies into the evolution of virulence in MDV1 in the face of blanket vaccination with imperfect vaccines that ameliorate disease but do not prevent infection and replication of virulent virus.

  17. Lymphocyte responses in the lungs of vaccinated pigs following homologous and heterologous influenza A virus challenge.

    Science.gov (United States)

    Vaccine associated enhanced respiratory disease (VAERD) has been described in pigs vaccinated with whole-inactivated influenza virus (WIV) following infection with heterologous influenza A virus (IAV). WIV vaccination elicits production of non-neutralizing antibody that is cross-reactive to the chal...

  18. EMERGING INFECTIOUS DISEASES. Actions Needed to Address the Challenges of Responding to Zika Virus Disease Outbreaks

    Science.gov (United States)

    2017-05-01

    required urgent and coordinated research.12 The Secretary of Health and Human Services...technical mechanism is required to manage the global response. However, the Zika virus and associated health outcomes remain a significant public health ...associated adverse health outcomes. Most of the 5,197 Zika virus disease cases reported by April 5, 2017 in the United States were associated with

  19. Dengue-1 Virus Envelope Glycoprotein Gene Expressed in Recombinant Baculovirus Elicits Virus-Neutralizing Antibody in Mice and Protects them from Virus Challenge

    Science.gov (United States)

    1991-01-01

    8217 terminus of E. When the recombinant virus was grown in Spodoptera frugiperda cells. about I mg of E antigen was made per 10’ cells. Recombinant E antigen...assay with DEN-I virus coprotein gene and its expression in Spodoptera hyperimmune mouse ascitic fluid. This heat-in- frugiperda cells activated...immunization, S. frugiperda cells infected with tion with BstNI (cuts at nucleotides 801 and recombinant baculovirus were pelleted. lysed by 2150). The

  20. 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.

  1. A Recombinant Rift Valley Fever Virus Glycoprotein Subunit Vaccine Confers Full Protection against Rift Valley Fever Challenge in Sheep.

    Science.gov (United States)

    Faburay, Bonto; Wilson, William C; Gaudreault, Natasha N; Davis, A Sally; Shivanna, Vinay; Bawa, Bhupinder; Sunwoo, Sun Young; Ma, Wenjun; Drolet, Barbara S; Morozov, Igor; McVey, D Scott; Richt, Juergen A

    2016-06-14

    Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease outbreaks in Africa and the Arabian Peninsula. The virus has great potential for transboundary spread due to the presence of competent vectors in non-endemic areas. There is currently no fully licensed vaccine suitable for use in livestock or humans outside endemic areas. Here we report the evaluation of the efficacy of a recombinant subunit vaccine based on the RVFV Gn and Gc glycoproteins. In a previous study, the vaccine elicited strong virus neutralizing antibody responses in sheep and was DIVA (differentiating naturally infected from vaccinated animals) compatible. In the current efficacy study, a group of sheep (n = 5) was vaccinated subcutaneously with the glycoprotein-based subunit vaccine candidate and then subjected to heterologous challenge with the virulent Kenya-128B-15 RVFV strain. The vaccine elicited high virus neutralizing antibody titers and conferred complete protection in all vaccinated sheep, as evidenced by prevention of viremia, fever and absence of RVFV-associated histopathological lesions. We conclude that the subunit vaccine platform represents a promising strategy for the prevention and control of RVFV infections in susceptible hosts.

  2. Vesicular stomatitis virus replicon expressing the VP2 outer capsid protein of bluetongue virus serotype 8 induces complete protection of sheep against challenge infection.

    Science.gov (United States)

    Kochinger, Stefanie; Renevey, Nathalie; Hofmann, Martin A; Zimmer, Gert

    2014-06-13

    Bluetongue virus (BTV) is an arthropod-borne pathogen that causes an often fatal, hemorrhagic disease in ruminants. Different BTV serotypes occur throughout many temperate and tropical regions of the world. In 2006, BTV serotype 8 (BTV-8) emerged in Central and Northern Europe for the first time. Although this outbreak was eventually controlled using inactivated virus vaccines, the epidemic caused significant economic losses not only from the disease in livestock but also from trade restrictions. To date, BTV vaccines that allow simple serological discrimination of infected and vaccinated animals (DIVA) have not been approved for use in livestock. In this study, we generated recombinant RNA replicon particles based on single-cycle vesicular stomatitis virus (VSV) vectors. Immunization of sheep with infectious VSV replicon particles expressing the outer capsid VP2 protein of BTV-8 resulted in induction of BTV-8 serotype-specific neutralizing antibodies. After challenge with a virulent BTV-8 strain, the vaccinated animals neither developed signs of disease nor showed viremia. In contrast, immunization of sheep with recombinant VP5 - the second outer capsid protein of BTV - did not confer protection. Discrimination of infected from vaccinated animals was readily achieved using an ELISA for detection of antibodies against the VP7 antigen. These data indicate that VSV replicon particles potentially represent a safe and efficacious vaccine platform with which to control future outbreaks by BTV-8 or other serotypes, especially in previously non-endemic regions where discrimination between vaccinated and infected animals is crucial.

  3. Effect of diluting Marek's disease vaccines on the outcomes of Marek's disease virus infection when challenged with highly virulent Marek's disease viruses.

    Science.gov (United States)

    Gimeno, Isabel M; Cortes, Aneg L; Montiel, Enrique R; Lemiere, Stephane; Pandiri, Arun K R

    2011-06-01

    Dilution of Marek's disease (MD) vaccines is a common practice in the field to reduce the cost associated with vaccination. In this study we have evaluated the effect of diluting MD vaccines on the protection against MD, vaccine and challenge MD virus (MDV) kinetics, and body weight when challenged with strains Md5 (very virulent MDV) and 648A (very virulent plus MDV) by contact at day of age. The following four vaccination protocols were evaluated in meat-type chickens: turkey herpesvirus (HVT) at manufacturer-recommended full dose; HVT diluted 1:10; HVT + SB-1 at the manufacturer-recommended full dose; and HVT + SB-1 diluted 1:10 for HVT and 1:5 for SB-1. Vaccine was administered at hatch subcutaneously. One-day-old chickens were placed in floor pens and housed together with ten 15-day-old chickens that had been previously inoculated with 500 PFU of either Md5 or 648A MDV strains. Chickens were individually identified with wing bands, and for each chicken samples of feather pulp and blood were collected at 1, 3, and 8 wk posthatch. Body weights were recorded at 8 wk for every chicken. Viral DNA load of wild-type MDV, SB-1, and HVT were evaluated by real time-PCR. Our results showed that dilution of MD vaccines can lead to reduced MD protection, reduced relative body weights, reduced vaccine DNA during the first 3 wk, and increased MDV DNA load. The detrimental effect of vaccine dilution was more evident in females than in males and was more evident when the challenge virus was 648A. However, lower relative body weights and higher MDV DNA load could be detected in chickens challenged with strain Md5, even in the absence of obvious differences in protection.

  4. The challenges of avian influenza virus:mechanism,epidemiology and control

    Institute of Scientific and Technical Information of China (English)

    George; F.GAO; Pang-Chui; SHAW

    2009-01-01

    Early 2009, eight human infection cases of H5N1 highly pathogenic avian influenza (HPAI) virus, with 5 death cases, were reported in China. This again made the world alert on a possible pandemic worldwide, probably caused by

  5. Virus genetic variations and evade from immune system, the present influenza challenges: review article

    Directory of Open Access Journals (Sweden)

    Shahla Shahsavandi

    2015-10-01

    Full Text Available The spread of influenza viruses in multiple bird and mammalian species is a worldwide serious threat to human and animal populations' health and raise major concern for ongoing pandemic in humans. Direct transmission of the avian viruses which have sialic acid specific receptors similar to human influenza viruses are a warning to the emergence of a new mutant strain that is likely to share molecular determinants to facilitate their replication in human host. So the emerge virus can be transmitted easily through person to person. The genetic variations of the influenza viruses, emerge and re-emerge of new antigenic variants, and transmission of avian influenza viruses to human may raise wide threat to public health and control of pandemic influenza. Vaccination, chemoprophylaxis with specific antiviral drugs, and personal protective non-pharmacological measures are tools to treat influenza virus infection. The emergence of drug resistant strains of influenza viruses under drug selective pressure and their limited efficacy in severe cases of influenza infections highlight the need to development of new therapies with alternative modes. In recent years several studies have been progressed to introduce components to be act at different stages of the viral life cycle with broad spectrum reactivity against mammalian and bird influenza subtypes. A wide variety of different antiviral strategies include inhibition of virus entry, blocking of viral replication or targeting of cellular signaling pathways have been explored. The current inactivated influenza vaccines are eliciting only B-cell responses. Application of the vaccines has been limited due to the emergence of the new virus antigenic variants. In recent decade development of gene vaccines by targeting various influenza virus proteins have been interested because significant potential for induction of both humoral and cell mediated immunity responses. Enhanced and directed immune responses to

  6. Antibody quality and protection from lethal Ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine.

    Directory of Open Access Journals (Sweden)

    Joseph E Blaney

    Full Text Available We have previously described the generation of a novel Ebola virus (EBOV vaccine platform based on (a replication-competent rabies virus (RABV, (b replication-deficient RABV, or (c chemically inactivated RABV expressing EBOV glycoprotein (GP. Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.

  7. Does human bocavirus infection depend on helper viruses? A challenging case report

    Directory of Open Access Journals (Sweden)

    Brockmann Michael

    2011-08-01

    Full Text Available Abstract A case of severe diarrhoea associated with synergistic human bocavirus type 1 (HBoV and human herpes virus type 6 (HHV6 is reported. The case supports the hypotheses that HBoV infection under clinical conditions may depend on helper viruses, or that HBoV replicates by a mechanism that is atypical for parvoviruses, or that HBoV infection can be specifically treated with cidofovir.

  8. Newcastle Disease Virus-Vectored H7 and H5 Live Vaccines Protect Chickens from Challenge with H7N9 or H5N1 Avian Influenza Viruses.

    Science.gov (United States)

    Liu, Qinfang; Mena, Ignacio; Ma, Jingjiao; Bawa, Bhupinder; Krammer, Florian; Lyoo, Young S; Lang, Yuekun; Morozov, Igor; Mahardika, Gusti Ngurah; Ma, Wenjun; García-Sastre, Adolfo; Richt, Juergen A

    2015-07-01

    Sporadic human infections by a novel H7N9 virus occurred over a large geographic region in China. In this study, we show that Newcastle disease virus (NDV)-vectored H7 (NDV-H7) and NDV-H5 vaccines are able to induce antibodies with high hemagglutination inhibition (HI) titers and completely protect chickens from challenge with the novel H7N9 or highly pathogenic H5N1 viruses, respectively. Notably, a baculovirus-expressed H7 protein failed to protect chickens from H7N9 virus infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Protection of mice against lethal challenge with 2009 H1N1 influenza A virus by 1918-like and classical swine H1N1 based vaccines.

    Directory of Open Access Journals (Sweden)

    Balaji Manicassamy

    2010-01-01

    Full Text Available The recent 2009 pandemic H1N1 virus infection in humans has resulted in nearly 5,000 deaths worldwide. Early epidemiological findings indicated a low level of infection in the older population (>65 years with the pandemic virus, and a greater susceptibility in people younger than 35 years of age, a phenomenon correlated with the presence of cross-reactive immunity in the older population. It is unclear what virus(es might be responsible for this apparent cross-protection against the 2009 pandemic H1N1 virus. We describe a mouse lethal challenge model for the 2009 pandemic H1N1 strain, used together with a panel of inactivated H1N1 virus vaccines and hemagglutinin (HA monoclonal antibodies to dissect the possible humoral antigenic determinants of pre-existing immunity against this virus in the human population. By hemagglutinination inhibition (HI assays and vaccination/challenge studies, we demonstrate that the 2009 pandemic H1N1 virus is antigenically similar to human H1N1 viruses that circulated from 1918-1943 and to classical swine H1N1 viruses. Antibodies elicited against 1918-like or classical swine H1N1 vaccines completely protect C57B/6 mice from lethal challenge with the influenza A/Netherlands/602/2009 virus isolate. In contrast, contemporary H1N1 vaccines afforded only partial protection. Passive immunization with cross-reactive monoclonal antibodies (mAbs raised against either 1918 or A/California/04/2009 HA proteins offered full protection from death. Analysis of mAb antibody escape mutants, generated by selection of 2009 H1N1 virus with these mAbs, indicate that antigenic site Sa is one of the conserved cross-protective epitopes. Our findings in mice agree with serological data showing high prevalence of 2009 H1N1 cross-reactive antibodies only in the older population, indicating that prior infection with 1918-like viruses or vaccination against the 1976 swine H1N1 virus in the USA are likely to provide protection against the 2009

  10. A vaccine against CCR5 protects a subset of macaques upon intravaginal challenge with simian immunodeficiency virus SIVmac251.

    Science.gov (United States)

    Van Rompay, Koen K A; Hunter, Zoe; Jayashankar, Kartika; Peabody, Julianne; Montefiori, David; LaBranche, Celia C; Keele, Brandon F; Jensen, Kara; Abel, Kristina; Chackerian, Bryce

    2014-02-01

    As an alternative to targeting human immunodeficiency virus (HIV), we have developed vaccines targeting CCR5, a self-protein critically involved in HIV replication and pathogenesis. By displaying peptides derived from CCR5 at high density on the surface of virus-like particles, we can efficiently induce high-titer IgG antibodies against this self-molecule. Here, we investigated whether prophylactic immunization of rhesus macaques with a particle-based vaccine targeting two regions of macaque CCR5 could prevent or suppress vaginal infection with highly virulent SIVmac251. Twelve macaques were vaccinated with a bacteriophage Qß-based vaccine targeting macaque CCR5 (Qß.CCR5). Six control animals were immunized with the Qß platform alone. All animals immunized with Qß.CCR5 developed high-titer anti-CCR5 antibody responses. Macaques were vaginally challenged with a high dose of SIVmac251. The mean peak viral RNA levels in the vaccinated groups were 30-fold lower than in the control group (10(6.8) versus 10(8.3) copies/ml plasma). Three of the 12 vaccinated macaques dramatically suppressed simian immunodeficiency virus (SIV) replication: peak viral loads were low (10(3) to 10(4) RNA copies/ml), and SIV RNA became undetectable from 6 weeks onward. No viral RNA or DNA could be detected in colon and lymph node biopsy specimens collected 13 months after challenge. In vivo depletion of CD8(+) cells failed to induce a viral rebound. However, once anti-CCR5 antibody responses had waned, the 3 animals became infected after intravaginal and/or intravenous rechallenge. In conclusion, vaccination against CCR5 was associated with dramatic suppression of virus replication in a subset (25%) of macaques. These data support further research of vaccination against CCR5 to combat HIV infection.

  11. Highly immunogenic prime–boost DNA vaccination protects chickens against challenge with homologous and heterologous H5N1 virus

    Directory of Open Access Journals (Sweden)

    Anna Stachyra

    2014-01-01

    Full Text Available Highly pathogenic avian influenza viruses (HPAIVs cause huge economic losses in the poultry industry because of high mortality rate in infected flocks and trade restrictions. Protective antibodies, directed mainly against hemagglutinin (HA, are the primary means of protection against influenza outbreaks. A recombinant DNA vaccine based on the sequence of H5 HA from the H5N1/A/swan/Poland/305-135V08/2006 strain of HPAIV was prepared. Sequence manipulation included deletion of the proteolytic cleavage site to improve protein stability, codon usage optimization to improve translation and stability of RNA in host cells, and cloning into a commercially available vector to enable expression in animal cells. Naked plasmid DNA was complexed with a liposomal carrier and the immunization followed the prime–boost strategy. The immunogenic potential of the DNA vaccine was first proved in broilers in near-to-field conditions resembling a commercial farm. Next, the protective activity of the vaccine was confirmed in SPF layer-type chickens. Experimental infections (challenge experiments indicated that 100% of vaccinated chickens were protected against H5N1 of the same clade and that 70% of them were protected against H5N1 influenza virus of a different clade. Moreover, the DNA vaccine significantly limited (or even eliminated transmission of the virus to contact control chickens. Two intramuscular doses of DNA vaccine encoding H5 HA induced a strong protective response in immunized chicken. The effective protection lasted for a minimum 8 weeks after the second dose of the vaccine and was not limited to the homologous H5N1 virus. In addition, the vaccine reduced shedding of the virus.

  12. Load of challenge Marek's disease virus DNA in blood as a criterion for early diagnosis of Marek's disease tumors.

    Science.gov (United States)

    Gimeno, Isabel M; Cortes, Aneg L; Silva, R F

    2008-06-01

    Outbreaks of Marek's disease (MD) in vaccinated flocks still occur sporadically and lead to economic losses. Unfortunately, adequate methods to predict MD outbreaks are lacking. In the present study, we have evaluated whether high load of challenge MD virus (MDV) DNA in peripheral blood could aid in the early diagnosis of MD and in monitoring efficacy of vaccines against MD. One experiment was conducted to simulate field conditions by combining various vaccines (turkey herpesvirus [HVT] and HVT + MDV serotype 2 [SB1]) and challenge viruses (GA, Md5, and 648A). Vaccine efficacy among our experimental groups ranged from 13.3% to 94.2%. Each chicken was sampled three times during the length of the experiment (3, 5, and 15 wk postchallenge [wpc]), and gross lesions were evaluated in chickens that died and at termination of the experiment. DNA was extracted from whole blood and buffy coats from each sample, and the load of challenge MDV DNA and HVT DNA were quantified by real-time polymerase chain reaction. Chickens that developed MD by the end of the experiment had higher load of challenge MDV DNA (threshold cycle [Ct] glyceraldehyde-3-phosphate dehydrogenase [GAPDH]/Ct glycoprotein B [gB] ratios of 1.0, 1.04, and 1.05 at 3, 5, and 15 wpc, respectively) than those that did not develop MD (Ct GAPDH/Ct gB ratios of 0.7, 0.69, and 0.46 at 3, 5, and 15 wpc, respectively). However, load of HVT DNA in blood was not correlated with the development of tumors (Ct GAPDH/Ct HVT ratios from 0.04 to 0.10 in both groups). Vaccinated groups with >75% protection had statistically significant less challenge DNA virus (Ct GAPDH/Ct gB ratios of 0.76, 0.70, and 0.45 at 3, 5, and 15 wpc, respectively) than less protected groups (Ct GAPDH/Ct gB ratios of 0.92, 0.97, and 0.85 at 3, 5, and 15 wpc, respectively). No differences in the load of HVT DNA could be found between protected and nonprotected groups at any time point of the study (Ct GAPDH/Ct HVT from 0.05 to 0.09 in both groups). Our

  13. Advances and challenges in the development of therapeutic DNA vaccines against hepatitis B virus infection.

    Science.gov (United States)

    Cova, Lucyna

    2014-01-01

    Despite the existence of an effective prophylactic vaccine, chronic hepatitis B virus (HBV) infection remains a major public health problem. Because very weak and functionally impaired virus-specific immune responses play a key role in the persistence of HBV infection, the stimulation of these responses appears to be of particular importance for virus clearance. In this regard DNA-based vaccination has emerged as novel, promising therapeutic approach for chronic hepatitis B. This review provides an update of preclinical studies in animal models (mouse, chimpanzee, duck, woodchuck), which evaluated the ability of DNA vaccines targeting hepadnaviral proteins to induce potent and sustained immune responses in naïve animals and to enhance virus clearance and break immune tolerance in chronic virus-carriers. Different strategies have been developed and evaluated in these models to optimize DNA vaccine including genetic adjuvants, combination with antiviral drugs, prime-boost regimens and plasmid delivery. The delivery of DNA by in vivo electroporation appears to be of particular interest for increase of vaccine potency in both small and large animal models. Based on the promising results generated in preclinical studies, first clinical trials of DNA vaccines have been initiated, although effective therapy of chronic hepatitis B awaits further improvements in vaccine efficacy.

  14. Humoral and cell-mediated immune responses in DNA immunized mink challenged with wild-type canine distemper virus

    DEFF Research Database (Denmark)

    Nielsen, Line; Søgaard, Mette; Karlskov-Mortensen, Peter

    2009-01-01

    The aim of the study was to investigate the different phases of the immune response after DNA immunization with the hemagglutinin and nucleoprotein genes from canine distemper virus (CDV). Although attenuated live CDV vaccines have effectively reduced the incidence of disease, canine distemper...... is still a problem worldwide. The broad host range of CDV creates a constant viral reservoir among wildlife animals. Our results demonstrated early humoral and cell-mediated immune responses (IFN-gamma) in DNA vaccinated mink compared to mock-vaccinated mink after challenge with a Danish wild-type CDV...

  15. A Systematic Approach towards Optimizing a Cohabitation Challenge Model for Infectious Pancreatic Necrosis Virus in Atlantic Salmon (Salmo salar L.).

    Science.gov (United States)

    Munang'andu, Hetron Mweemba; Santi, Nina; Fredriksen, Børge Nilsen; Løkling, Knut-Egil; Evensen, Øystein

    2016-01-01

    A cohabitation challenge model was developed for use in evaluating the efficacy of vaccines developed against infectious pancreatic necrosis virus (IPNV) in Atlantic salmon (Salmo salar L) using a stepwise approach. The study involved identifying a set of input variables that were optimized before inclusion in the model. Input variables identified included the highly virulent Norwegian Sp strain NVI015-TA encoding the T217A221 motif having the ability to cause >90% mortality and a hazard risk ratio of 490.18 (p75% in the unvaccinated fish in order to attain a high discriminatory capacity (DC) between the vaccinated and control fish as a measure of vaccine efficacy. The model shows the importance of using highly susceptible fish to IPNV in the optimization of challenge models by showing that highly susceptible fish had a better DC of differentiating vaccine protected fish from the unvaccinated control fish than the less susceptible fish. Once all input variables were optimized, the model was tested for its reproducibility by generating similar results from three independent cohabitation challenge trials using the same input variables. Overall, data presented here show that the cohabitation challenge model developed in this study is reproducible and that it can reliably be used to evaluate the efficacy of vaccines developed against IPNV in Atlantic salmon. We envision that the approach used here will open new avenues for developing optimal challenge models for use in evaluating the efficacy of different vaccines used in aquaculture.

  16. [Zika virus outbreak in Latin America: what are the challenges for French Guiana in April 2016?].

    Science.gov (United States)

    Epelboin, L; Douine, M; Carles, G; Villemant, N; Nacher, M; Rousset, D; Djossou, F; Mosnier, E

    2016-05-01

    Started in 2015 in Brazil, an outbreak linked to a little known arbovirus, Zika virus spread throughout Latin America. This virus, considered until recently as responsible of only mild symptoms, made mention of previously unsuspected complications, with severe neurological manifestations in adults and malformations of the central nervous system, including microcephaly, in newborns of mother infected during the pregnancy. While the continent is more accustomed to the succession of arbovirus epidemics, suspected complications and the many unknowns keys of the latter arriving raise many public health issues. French Guiana, a French territory located in the north-east of the continent, combines both European level of resources and climate and issues specific to the Amazon region and Latin America. We discuss here the issues for 2016 Zika virus epidemic in our region, many of them are generalizable to neighboring countries.

  17. One Medicine One Science: a framework for exploring challenges at the intersection of animals, humans, and the environment.

    Science.gov (United States)

    Travis, Dominic A; Sriramarao, P; Cardona, Carol; Steer, Clifford J; Kennedy, Shaun; Sreevatsan, Srinand; Murtaugh, Michael P

    2014-12-01

    Characterizing the health consequences of interactions among animals, humans, and the environment in the face of climatic change, environmental disturbance, and expanding human populations is a critical global challenge in today's world. Exchange of interdisciplinary knowledge in basic and applied sciences and medicine that includes scientists, health professionals, key sponsors, and policy experts revealed that relevant case studies of monkeypox, influenza A, tuberculosis, and HIV can be used to guide strategies for anticipating and responding to new disease threats such as the Ebola and Chickungunya viruses, as well as to improve programs to control existing zoonotic diseases, including tuberculosis. The problem of safely feeding the world while preserving the environment and avoiding issues such as antibiotic resistance in animals and humans requires cooperative scientific problem solving. Food poisoning outbreaks resulting from Salmonella growing in vegetables have demonstrated the need for knowledge of pathogen evolution and adaptation in developing appropriate countermeasures for prevention and policy development. Similarly, pesticide use for efficient crop production must take into consideration bee population declines that threaten the availability of the two-thirds of human foods that are dependent on pollination. This report presents and weighs the objective merits of competing health priorities and identifies gaps in knowledge that threaten health security, to promote discussion of major public policy implications such that they may be decided with at least an underlying platform of facts. © 2014 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

  18. Virus removal retention challenge tests performed at lab scale and pilot scale during operation of membrane units.

    Science.gov (United States)

    Humbert, H; Machinal, C; Labaye, Ivan; Schrotter, J C

    2011-01-01

    The determination of the virus retention capabilities of UF units during operation is essential for the operators of drinking water treatment facilities in order to guarantee an efficient and stable removal of viruses through time. In previous studies, an effective method (MS2-phage challenge tests) was developed by the Water Research Center of Veolia Environnement for the measurement of the virus retention rates (Log Removal Rate, LRV) of commercially available hollow fiber membranes at lab scale. In the present work, the protocol for monitoring membrane performance was transferred from lab scale to pilot scale. Membrane performances were evaluated during pilot trial and compared to the results obtained at lab scale with fibers taken from the pilot plant modules. PFU culture method was compared to RT-PCR method for the calculation of LRV in both cases. Preliminary tests at lab scale showed that both methods can be used interchangeably. For tests conducted on virgin membrane, a good consistency was observed between lab and pilot scale results with the two analytical methods used. This work intends to show that a reliable determination of the membranes performances based on RT-PCR analytical method can be achieved during the operation of the UF units.

  19. Protective efficacy of multivalent replication-abortive vaccine strains in horses against African horse sickness virus challenge.

    Science.gov (United States)

    Lulla, Valeria; Losada, Andres; Lecollinet, Sylvie; Kerviel, Adeline; Lilin, Thomas; Sailleau, Corinne; Beck, Cecile; Zientara, Stephan; Roy, Polly

    2017-07-24

    African horse sickness virus (AHSV) is an orbivirus, a member of the Reoviridae family. Nine different serotypes have been described so far. AHSV is vectored by Culicoides spp. to equids, causing high mortality, particularly in horses, with considerable economic impacts. For development of a safe attenuated vaccine, we previously established an efficient reverse genetics (RG) system to generate Entry Competent Replication-Abortive (ECRA) virus strains, for all nine serotypes and demonstrated the vaccine potential of these strains in type I interferon receptor (IFNAR)-knockout mice. Here, we evaluated the protective efficacies of these ECRA viruses in AHSV natural hosts. One monoserotype (ECRA.A4) vaccine and one multivalent cocktail (ECRA.A1/4/6/8) vaccine were tested in ponies and subsequently challenged with a virulent AHSV4. In contrast to control animals, all vaccinated ponies were protected and did not develop severe clinical symptoms of AHS. Furthermore, the multivalent cocktail vaccinated ponies produced neutralizing antibodies against all serotypes present in the cocktail, and a foal born during the trial was healthy and had no viremia. These results validate the suitability of these ECRA strains as a new generation of vaccines for AHSV. Copyright © 2017. Published by Elsevier Ltd.

  20. Horizontal transmission of nervous necrosis virus between turbot Scophthalmus maximus and Atlantic cod Gadus morhua using cohabitation challenge.

    Science.gov (United States)

    Korsnes, Kjetil; Karlsbakk, Egil; Nylund, Are; Nerland, Audun Helge

    2012-05-15

    Experimental horizontal transmission of nervous necrosis virus (NNV) originating from halibut Hippoglossus hippoglossus was studied through cohabitation of intraperitoneally (i.p.) injected fish with uninfected fish for 125 d. The experimental groups consisted of i.p. injected turbot Scophthalmus maximus or i.p. injected Atlantic salmon Salmo salar with turbot, salmon or Atlantic cod Gadus morhua cohabitants. The initial weights were cod 10 g, salmon 40 g and turbot 3 g. NNV was detected in brain, eye and spleen by real-time reverse transcriptase PCR (qRT-PCR) in cod cohabitated with i.p. injected turbot after 90 and 125 d, suggesting NNV infection was transmitted horizontally from the turbot to cod. NNV was not detected in salmon that were cohabitated with i.p. challenged turbot or salmon. This study shows that NNV strains belonging to the Barfin Flounder Nervous Necrosis Virus (BFNNV) clade may be transmitted from halibut to cod via water. Hence there is a potential risk of horizontal transmission of the virus from farmed halibut to farmed and wild cod. The lack of detection of NNV in cohabitant salmon suggests that this fish species is less susceptible than cod, or not susceptible, to horizontal NNV transmission. This result might be influenced by the size of salmon, viral load in i.p. injected cohabitants or insufficient duration of the experiment.

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

    Directory of Open Access Journals (Sweden)

    Mark Page

    Full Text Available 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.

  2. A humanised murine monoclonal antibody protects mice from Venezuelan equine encephalitis virus, Everglades virus and Mucambo virus when administered up to 48 h after airborne challenge

    Energy Technology Data Exchange (ETDEWEB)

    O' Brien, Lyn M., E-mail: lmobrien@dstl.gov.uk; Goodchild, Sarah A.; Phillpotts, Robert J.; Perkins, Stuart D.

    2012-05-10

    Currently there are no licensed antiviral treatments for the Alphaviruses Venezuelan equine encephalitis virus (VEEV), Everglades virus and Mucambo virus. We previously developed a humanised version of the mouse monoclonal antibody 1A3B-7 (Hu1A3B-7) which exhibited a wide range of reactivity in vitro and was able to protect mice from infection with VEEV. Continued work with the humanised antibody has now demonstrated that it has the potential to be a new human therapeutic. Hu1A3B-7 successfully protected mice from infection with multiple Alphaviruses. The effectiveness of the humanisation process was determined by assessing proliferation responses in human T-cells to peptides derived from the murine and humanised versions of the V{sub H} and V{sub L} domains. This analysis showed that the number of human T-cell epitopes within the humanised antibody had been substantially reduced, indicating that Hu1A3B-7 may have reduced immunogenicity in vivo.

  3. Protection of horses from West Nile virus Lineage 2 challenge following immunization with a whole, inactivated WNV lineage 1 vaccine.

    Science.gov (United States)

    Bowen, Richard A; Bosco-Lauth, Angela; Syvrud, Kevin; Thomas, Anne; Meinert, Todd R; Ludlow, Deborah R; Cook, Corey; Salt, Jeremy; Ons, Ellen

    2014-09-22

    Over the last years West Nile virus (WNV) lineage 2 has spread from the African to the European continent. This study was conducted to demonstrate efficacy of an inactivated, lineage 1-based, WNV vaccine (Equip WNV) against intrathecal challenge of horses with a recent isolate of lineage 2 WNV. Twenty horses, sero-negative for WNV, were enrolled and were randomly allocated to one of two treatment groups: an unvaccinated control group (T01, n=10) and a group administered with Equip WNV (T02, n=10). Horses were vaccinated at Day 0 and 21 and were challenged at day 42 with WNV lineage 2, Nea Santa/Greece/2010. Personnel performing clinical observations were blinded to treatment allocation. Sixty percent of the controls had to be euthanized after challenge compared to none of the vaccinates. A significantly lower percentage of the vaccinated animals showed clinical disease (two different clinical observations present on the same day) on six different days of study and the percentage of days with clinical disease was significantly lower in the vaccinated group. A total of 80% of the non-vaccinated horses showed viremia while only one vaccinated animal was positive by virus isolation on a single occasion. Vaccinated animals started to develop antibodies against WNV lineage 2 from day 14 (2 weeks after the first vaccination) and at day 42 (the time of onset of immunity) they had all developed a strong antibody response. Histopathology scores for all unvaccinated animals ranged from mild to very severe in each of the tissues examined (cervical spinal cord, medulla and pons), whereas in vaccinated horses 8 of 10 animals had no lesions and 2 had minimal lesions in one tissue. In conclusion, Equip WNV significantly reduced the number of viremic horses, the duration and severity of clinical signs of disease and mortality following challenge with lineage 2 WNV.

  4. Marek's disease virus isolates with unusual tropism and virulence for ocular tissues: clinical findings, challenge studies and pathological features.

    Science.gov (United States)

    Ficken, M D; Nasisse, M P; Boggan, G D; Guy, J S; Wages, D P; Witter, R L; Rosenberger, J K; Nordgren, R M

    1991-09-01

    Outbreaks of Marek's disease (MD) were diagnosed in two flocks from the same company. Clinical signs, mainly blindness (>90%), but also depression, mild paralysis, and 11 to 12% mortality by 20 weeks of age were observed. MD virus, serotype 1 was isolated. The isolates were designated NC-1 (flock 1) and NC-2 (flock 2). Challenge experiments were conducted with these isolates and with two reference MD virus strains (JM/102W and Md5) in unvaccinated, turkey herpesvirus- (HVT) vaccinated and bivalent- (HVT and SB-1) vaccinated chickens. Blindness, gross ocular lesions and tumour formation were observed in a high proportion of all groups challenged with NC-1 and NC-2 when compared with chickens challenged with JM/102W and Md5. In chickens challenged with isolates NC-1 and NC-2, corneal changes included oedema, midstromal cellular infiltration consisting of macrophages, lymphocytes, plasma cells and lesser numbers of heterophils, collagen degeneration and keratic precipitates consisting primarily of macrophages covering the central endothelium. Eosinophilic intranuclear inclusion bodies were present in mononuclear cells infiltrating the cornea. Changes in the uveal tract consisted of inflammatory cell infiltrates similar to those present in the cornea. Retinal lesions included disruption of the retinal pigmented epithelium, inflammatory cell infiltration in the subretinal space, photoreceptor degeneration and in severely affected eyes, necrosis of retinal cellular elements. Pecten changes consisted of necrosis and mononuclear cell infiltration. Intranuclear inclusion bodies were abundantly present in cells of the retina's ganglion and inner nuclear cell layers. The unusual clinical manifestation of MD, the unusual tropism and virulence of NC-1 and NC-2 for ocular tissues and the incomplete protection afforded by conventional vaccination suggest that these isolates may be new pathotypes.

  5. West Nile Virus Challenge Alters the Transcription Profiles of Innate Immune genes in Rabbit Peripheral Blood Mononuclear Cells

    Directory of Open Access Journals (Sweden)

    Muhammad Jasim eUddin

    2015-12-01

    Full Text Available The peripheral innate immune response to West Nile virus (WNV is crucial for control of virus spread to the central nervous system. Therefore, transcriptomes encoding the innate immune response proteins against WNV were investigated in peripheral blood mononuclear cells (PBMCs of New Zealand White rabbits, a recently established novel rabbit model for WNV pathogenesis studies. PBMCs were challenged with an Australian WNV strain, WNVNSW2011, in vitro and mRNA expression of selected immune response genes were quantified at 2h, 6h, 12h and 24h post infection (pi using qRT-PCR. Compared to mock-inoculated PBMCs, WNV-stimulated PBMCs expressed high levels of interferon (IFN alpha (IFNA, gamma (IFNG, IL6, IL12, IL22, CXCL10 and pentraxin 3 (PTX3 mRNA. Likewise, TLR1, 2, 3, 4, 6 and 10 mRNA became up-regulated with highest expression seen for TLR3, 4 and 6. TLRs-signalling downstream genes (MyD88, STAT1, TRAF3, IRF7 and IRF9 subsequently became up-regulated. The high expression of IFNs, TLR3, TLR4, TRAF3, STAT1, IRF7 and IRF9 are in accordance with antiviral activities, while expression of TNFA, HO1, iNOS, caspase 3 and 9 transcripts suggests the involvement of oxidative stress and apoptosis in WNV stimulated rabbit PBMCs, respectively. The level of WNVNSW2011 RNA increased at 24h pi in PBMCs challenged with virus in vitro compared to input virus. The expression dynamics of selected genes were validated in PBMCs from rabbits experimentally infected with WNV in vivo. Higher expression of IFNA, IFN beta (IFNB, IFNG, TNFA, IL6, IL22, PTX3, TLR3 & TLR4, IRF7, IRF9, STST1, TRAF3, caspase 3 and caspase 9 were seen in PBMCs from WNV infected rabbits on day 3 post intradermal virus inoculation compared to PBMCs from uninfected control rabbits. This study highlights the array of cytokines and TLRs involved in the host innate immune response to WNV in the rabbit leukocytes, and suggests that these cells may be a useful in vitro model for WNV infection study.

  6. Infants with Congenital Zika Virus Infection: A New Challenge for Early Intervention Professionals

    Science.gov (United States)

    Porter, Sallie; Mimm, Nancy

    2017-01-01

    Zika virus infection-associated microcephaly has generated public health and media concern. Unsettling images emerging from Brazil of infants with abnormally small heads have raised concern among women of childbearing age, international travelers, government officials, and health care professionals. The World Health Organization declared the most…

  7. Immune Serum Produced by DNA Vaccination Protects Hamsters against Lethal Respiratory Challenge with Andes Virus

    Science.gov (United States)

    2008-02-01

    pulmonary syndrome in Argentina. Possibility of person to person transmission. Medicina (Buenos Aires) 56: 709–711. 8. Ferres, M., P. Vial, C. Marco, L...transmission of Andes virus. Medicina (Buenos Aires) 58(Suppl. 1):27–36. 20. Padula, P. J., A. Edelstein, S. D. Miguel, N. M. Lopez, C. M. Rossi, and R

  8. Inactivated recombinant plant virus protects dogs from a lethal challenge with canine parvovirus

    DEFF Research Database (Denmark)

    Langeveld, J.P.M.; Brennan, F.R.; Martinez-Torrecuadrada, J.L.

    2001-01-01

    A vaccine based upon a recombinant plant virus (CPMV-PARVO1), displaying a peptide derived from the VP2 capsid protein of canine parvovirus (CPV), has previously been described. To date, studies with the vaccine have utilized viable plant chimaeric particles (CVPs). In this study, CPMV-PARVO1...

  9. Infants with Congenital Zika Virus Infection: A New Challenge for Early Intervention Professionals

    Science.gov (United States)

    Porter, Sallie; Mimm, Nancy

    2017-01-01

    Zika virus infection-associated microcephaly has generated public health and media concern. Unsettling images emerging from Brazil of infants with abnormally small heads have raised concern among women of childbearing age, international travelers, government officials, and health care professionals. The World Health Organization declared the most…

  10. Zika Virus and Microcephaly: Challenges for a Long-Term Agenda.

    Science.gov (United States)

    Duarte Dos Santos, Claudia Nunes; Goldenberg, Samuel

    2016-07-01

    Since its introduction in Brazil in 2015, Zika virus (ZIKV) has begun to spread worldwide. One of the major infection outcomes is related to congenital malformations, but little is known about the pathogenicity of ZIKV. Here we discuss concerns about the ongoing ZIKV epidemic in the context of academic research, politics, and society.

  11. An inactivated influenza D virus vaccine partially protects cattle from respiratory disease caused by homologous challenge

    Science.gov (United States)

    Originally isolated from swine, the proposed influenza D virus has since been shown to be common in cattle. Inoculation of IDV to naïve calves resulted in mild respiratory disease histologically characterized by tracheitis. As several studies have associated the presence of IDV with acute bovine r...

  12. Recombinant adenovirus expressing the haemagglutinin of Peste des petits ruminants virus (PPRV) protects goats against challenge with pathogenic virus; a DIVA vaccine for PPR.

    Science.gov (United States)

    Herbert, Rebecca; Baron, Jana; Batten, Carrie; Baron, Michael; Taylor, Geraldine

    2014-02-26

    Peste des petits ruminants virus (PPRV) is a morbillivirus that can cause severe disease in sheep and goats, characterised by pyrexia, pneumo-enteritis, and gastritis. The socio-economic burden of the disease is increasing in underdeveloped countries, with poor livestock keepers being affected the most. Current vaccines consist of cell-culture attenuated strains of PPRV, which induce a similar antibody profile to that induced by natural infection. Generation of a vaccine that enables differentiation of infected from vaccinated animals (DIVA) would benefit PPR control and eradication programmes, particularly in the later stages of an eradication campaign and for countries where the disease is not endemic. In order to create a vaccine that would enable infected animals to be distinguished from vaccinated ones (DIVA vaccine), we have evaluated the immunogenicity of recombinant fowlpox (FP) and replication-defective recombinant human adenovirus 5 (Ad), expressing PPRV F and H proteins, in goats. The Ad constructs induced higher levels of virus-specific and neutralising antibodies, and primed greater numbers of CD8+ T cells than the FP-vectored vaccines. Importantly, a single dose of Ad-H, with or without the addition of Ad expressing ovine granulocyte macrophage colony-stimulating factor and/or ovine interleukin-2, not only induced strong antibody and cell-mediated immunity but also completely protected goats against challenge with virulent PPRV, 4 months after vaccination. Replication-defective Ad-H therefore offers the possibility of an effective DIVA vaccine.

  13. Gumboro disease: evaluation of serological and anatomopathological responses in vaccinated broiler chickens challenged with very virulent virus strain

    Directory of Open Access Journals (Sweden)

    Bolis DA

    2003-01-01

    Full Text Available This paper describes the effects of a strong type of vaccine - Moulthrop G603 º and an intermediate-plus type of vaccine - 228E º in meat-type chickens challenged with a very virulent strain of infectious bursal disease virus (vvIBDV. Blood samples and bursa of Fabricius were taken weekly up to 42 days of age. It was concluded that bursa of Fabricius weight, bursa weight:body weight ratio, body weight and antibody titer evaluated before and after challenge with vvIBDV were not enough to consistently and conclusively differentiate or estimate the protection given by vaccination. Quantitative evaluation of injury intensity and the number of altered lymphoid follicles revealed that Moulthrop G603 caused moderate microscopic lesions in one out of seven birds vaccinated at 14 days of age, while 228E vaccine did not induce IBD-typical microscopic lesions in the bursa of Fabricius. Good protection against bursal microscopic lesions was obtained when a strong type of vaccine was used before challenging with vvIBDV. It was concluded that quantitative evaluation of microscopic lesions might be useful to measure the injury induced by vaccinal IBDV, as well as the level of protection and/or immunosuppression induced by IBDV challenge in vaccinated and non-vaccinated chickens.

  14. Experimental challenge of a peridomestic avian species, European Starlings (Sturnus vulgaris), with novel Influenza A H7N9 virus from China

    Science.gov (United States)

    Hall, Jeffrey S.; Ip, Hon S.; Teslaa, Joshua L.; Nashold, Sean W.; Dusek, Robert

    2016-01-01

    In 2013 a novel avian influenza H7N9 virus was isolated from several critically ill patients in China, and infection with this virus has since caused more than 200 human deaths. Live poultry markets are the likely locations of virus exposure to humans. Peridomestic avian species also may play important roles in the transmission and maintenance of H7N9 at live poultry markets. We experimentally challenged wild European Starlings (Sturnus vulgaris) with the novel H7N9 virus and measured virus excretion, clinical signs, and infectious dose. We found that European Starlings can be infected with this virus when inoculated with relatively high doses, and we predict that infected birds excrete sufficient amounts of virus to transmit to other birds, including domestic chickens. Infected European Starlings showed no clinical signs or mortality after infection with H7N9. This abundant peridomestic bird may be a source of the novel H7N9 virus in live poultry markets and may have roles in virus transmission to poultry and humans.

  15. Signifiance of hepatitis E virus infection in HIV-infected patients: a challenging issue

    Directory of Open Access Journals (Sweden)

    Amitis Ramezani

    2015-05-01

    Full Text Available Hepatitis E virus (HEV is a small, single-stranded, non-enveloped RNA virus and belongs to the genus Hepevirus in the Hepeviridae family. Currently, the HEV infection is the most frequent cause of acute hepatitis in the world. In recent years, some studies have been demonstrated that immunosuppressed cases, such organ transplant recipients, cases with HIV infection and patients with hematological malignancies are at risk of HEV infection. But it is not clear whether HEV infection is a major concern in HIV infected patients or not? The answer has considerable significance, because HIV and HEV infection are now both highly endemic in many parts of the world. The purpose of this review is to provide data on the prevalence of HEV infection in HIV infected patients for determination of the significance of HEV/HIV co-infection.

  16. Protection of Hamsters by Venezuelan Equine Encephalitis Virus Candidate Vaccine V3526 Against Lethal Challenge by Mosquito Bite and Intraperitoneal Injection

    Science.gov (United States)

    2008-01-01

    the furin cleavage site in PE2 as well as a suppressor mutation in E1, was shown to protect mice, hamsters, and nonhuman primates challenged either by...previously to protect mice, hamsters, and nonhuman primates , there was concern that virus intro- duced by an infected mosquito might be more pathogenic than...and Rift Valley fever virus. Am J Trop Med Hyg 32: 1154–1163. 12. Karabatsos N, ed., 1985. International Catalogue of Arboviruses including Certain

  17. Addressing the Challenges of Hepatitis C Virus Resistance and Treatment Failure

    OpenAIRE

    Che C. Colpitts; Baumert, Thomas F.

    2016-01-01

    Chronic hepatitis C is a major cause of chronic liver disease, including liver cirrhosis and hepatocellular carcinoma. The development of direct-acting antivirals (DAAs) revolutionized hepatitis C virus (HCV) treatment by offering genuine prospects for the first comprehensive cure of a chronic viral infection in humans. While antiviral resistance is a significant limitation for interferon-based therapies, resistance and treatment failure still appear to be present in a small fraction of patie...

  18. Monoclonal anti-envelope antibody AP33 protects humanized mice against a patient-derived hepatitis C virus challenge.

    Science.gov (United States)

    Desombere, Isabelle; Fafi-Kremer, Samira; Van Houtte, Freya; Pessaux, Patrick; Farhoudi, Ali; Heydmann, Laura; Verhoye, Lieven; Cole, Sarah; McKeating, Jane A; Leroux-Roels, Geert; Baumert, Thomas F; Patel, Arvind H; Meuleman, Philip

    2016-04-01

    End-stage liver disease (ESLD) caused by hepatitis C virus (HCV) infection is a major indication for liver transplantation. However, immediately after transplantation, the liver graft of viremic patients universally becomes infected by circulating virus, resulting in accelerated liver disease progression. Currently available direct-acting antiviral therapies have reduced efficacy in patients with ESLD and prophylactic strategies to prevent HCV recurrence are still highly needed. In this study, we compared the ability of two broadly reactive monoclonal antibodies (mAbs), designated 3/11 and AP33, recognizing a distinct, but overlapping, epitope in the viral E2 glycoprotein to protect humanized mice from a patient-derived HCV challenge. Their neutralizing activity was assessed using the HCV pseudoparticles and cell-culture-derived HCV systems expressing multiple patient-derived envelopes and a human-liver chimeric mouse model. HCV RNA was readily detected in all control mice challenged with a patient-derived HCV genotype 1b isolate, whereas 3 of 4 AP33-treated mice were completely protected. In contrast, only one of four 3/11-treated mice remained HCV-RNA negative throughout the observation period, whereas the other 3 had a viral load that was indistinguishable from that in the control group. The increased in vivo efficacy of AP33 was in line with its higher affinity and neutralizing capacity observed in vitro. Although mAbs AP33 and 3/11 target the same region in E2, only mAb AP33 can efficiently protect from challenge with a heterologous HCV population in vivo. Given that mAb AP33 efficiently neutralizes viral variants that escaped the humoral immune response and reinfected the liver graft of transplant patients, it may be a valuable candidate to prevent HCV recurrence. In addition, our data are valuable for the design of a prophylactic vaccine. © 2015 by the American Association for the Study of Liver Diseases.

  19. Increased expression of Interleukin-6 related to nephritis in chickens challenged with an Avian infectious bronchitis virus variant

    Directory of Open Access Journals (Sweden)

    Filipe S. Fernando

    2015-03-01

    Full Text Available A Brazilian field isolate (IBV/Brazil/PR05 of avian infectious bronchitis virus (IBV, associated with development of nephritis in chickens, was previously genotyped as IBV variant after S1 gene sequencing. The aim of this study was to evaluate the levels of IL-6 in kidneys and trachea of birds vaccinated and challenged with IBV/Brazil/PR05 strain, correlating these results with scores of microscopic lesions, specific IBV antigen detection and viral load. The up-regulation of IL-6 and the increased levels of viral load on renal and tracheal samples were significantly correlated with scores of microscopic lesions. Reduced levels of viral load were detected in kidneys of birds previously vaccinated and challenged, compared to non-vaccinated challenged group, although markedly microscopic lesions were observed for both groups. The expression of IL-6, present both in the kidney and in the tracheas, was dependent on the load of the virus present in the tissue, and the development of lesions was related with IL-6 present in the tissues. These data suggest that variant IBV/Brazil/PR05 can induce the expression of proinflammatory cytokines in a manner correlated with viral load and increased IL-6 is involved in the tissue with the influx of inflammatory cells and subsequent nephritis. This may contribute with a model to the development of immunosuppressive agents of IL-6 to prevent acute inflammatory processes against infection with IBV and perhaps other coronaviruses, as well as contribute to the understanding of the immunopathogenesis of IBV nephropatogenic strains.

  20. Response of ELA-A1 horses immunized with lipopeptide containing an equine infectious anemia virus ELA-A1-restricted CTL epitope to virus challenge.

    Science.gov (United States)

    Ridgely, Sherritta L; Zhang, Baoshan; McGuire, Travis C

    2003-01-17

    Lipopeptide containing an ELA-A1-restricted cytotoxic T lymphocyte (CTL) epitope from the envelope surface unit (SU) protein of the EIAV(WSU5) strain was used to immunize three horses having the ELA-A1 haplotype. Peptide-specific ELA-A1-restricted CTL were induced in all three horses, although these were present transiently in PBMC. These horses were further immunized with lipopeptide containing the corresponding CTL epitope from the EIAV(PV) strain. Then, the three immunized horses and three non-immunized horses were challenged by intravenous inoculation with 300 TCID(50) EIAV(PV). All horses developed cell free viremia, fever and thrombocytopenia. However, there was a statistically lower fever and thrombocytopenia severity score in the immunized group. Shorter duration of plasma viral load in two of the three immunized horses likely explains the less severe clinical disease in this group. Results indicate that lipopeptide immunization had a protective effect against development of clinical disease following virus challenge.

  1. Chikungunya Virus

    Science.gov (United States)

    ... Gaines, PhD, MPH, MA, CHES Differentiating Chikungunya From Dengue: A Clinical Challenge For Travelers CDC Travelers' Health Chikungunya Virus Home Prevention Transmission Symptoms & Treatment Geographic Distribution Chikungunya virus in ...

  2. Human Immunodeficiency Virus and Leprosy Coinfection: Challenges in Resource-Limited Setups

    Directory of Open Access Journals (Sweden)

    Charles M. Kwobah

    2012-01-01

    Full Text Available Mycobacteria leprae(leprosy and HIV coinfection are rare in Kenya. This is likely related to the low prevalence (1 per 10,000 of population of leprosy. Because leprosy is no longer a public health challenge there is generally a low index of suspicion amongst clinicians for its diagnosis. Management of a HIV-1-leprosy-coinfected individual in a resource-constrained setting is challenging. Some of these challenges include difficulties in establishing a diagnosis of leprosy; the high pill burden of cotreatment with both antileprosy and antiretroviral drugs (ARVs; medications’ side effects; drug interactions; scarcity of drug choices for both diseases. This challenge is more profound when managing a patient who requires second-line antiretroviral therapy (ART. We present an adult male patient coinfected with HIV and leprosy, who failed first-line antiretroviral therapy (ART and required second-line treatment. Due to limited choices in antileprosy drugs available, the patient received monthly rifampicin and daily lopinavir-/ritonavir-based antileprosy and ART regimens, respectively. Six months into his cotreatment, he seemed to have adequate virological control. This case report highlights the challenges of managing such a patient.

  3. An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses

    Directory of Open Access Journals (Sweden)

    Chan Chris CS

    2010-01-01

    Full Text Available Abstract Background A growing concern has raised regarding the pandemic potential of the highly pathogenic avian influenza (HPAI H5N1 viruses. Consequently, there is an urgent need to develop an effective and safe vaccine against the divergent H5N1 influenza viruses. In the present study, we designed a tetra-branched multiple antigenic peptide (MAP-based vaccine, designated M2e-MAP, which contains the sequence overlapping the highly conserved extracellular domain of matrix protein 2 (M2e of a HPAI H5N1 virus, and investigated its immune responses and cross-protection against different clades of H5N1 viruses. Results Our results showed that M2e-MAP vaccine induced strong M2e-specific IgG antibody responses following 3-dose immunization of mice with M2e-MAP in the presence of Freunds' or aluminium (alum adjuvant. M2e-MAP vaccination limited viral replication and attenuated histopathological damage in the challenged mouse lungs. The M2e-MAP-based vaccine protected immunized mice against both clade1: VN/1194 and clade2.3.4: SZ/406H H5N1 virus challenge, being able to counteract weight lost and elevate survival rate following lethal challenge of H5N1 viruses. Conclusions These results suggest that M2e-MAP presenting M2e of H5N1 virus has a great potential to be developed into an effective subunit vaccine for the prevention of infection by a broad spectrum of HPAI H5N1 viruses.

  4. Challenges to the development of vaccines to hepatitis C virus that elicit neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Heidi Edelgard Drummer

    2014-07-01

    Full Text Available Despite 20 years of research, a vaccine to prevent hepatitis C virus (HCV infection has not been developed. A vaccine to prevent HCV will need to induce broadly reactive immunity able to prevent infection by the 7 genetically and antigenically distinct genotypes circulating world-wide. Hepatitis C virus encodes two surface exposed glycoproteins, E1 and E2 that function as a heterodimer to mediate viral entry. Neutralizing antibodies (NAbs to both E1 and E2 have been described with the major NAb target being E2. The function of E2 is to attach virions to host cells via cell surface receptors that include, but is not limited to, the tetraspanin CD81 and scavenger receptor B class I. However, E2 has developed a number of immune evasion strategies to limit the effectiveness of the NAb response and possibly limit the ability of the immune system to generate potent NAbs in natural infection. Hypervariable regions that shield the underlying core domain, subdominant neutralization epitopes and glycan shielding combine to make E2 a difficult target for the immune system. This review summarizes recent information on the role of neutralizing antibodies to prevent HCV infection, the targets of the neutralizing antibody response and structural information on glycoprotein E2 in complex with neutralizing antibodies. This new information should provide a framework for the rational design of new vaccine candidates that elicit highly potent broadly reactive NAbs to prevent HCV infection.

  5. Preventive and therapeutic challenges in combating Zika virus infection: are we getting any closer?

    Science.gov (United States)

    Singh, Meera V; Weber, Emily A; Singh, Vir B; Stirpe, Nicole E; Maggirwar, Sanjay B

    2017-01-23

    The neuroteratogenic nature of Zika Virus (ZIKV) infection has converted what would have been a tropical disease into a global threat. Zika is transmitted vertically via infected placental cells especially in the first and second trimesters. In the developing central nervous system (CNS), ZIKV can infect and induce apoptosis of neural progenitor cells subsequently causing microcephaly as well as other neuronal complications in infants. Its ability to infect multiple cell types (placental, dermal, and neural) and increased environmental stability as compared to other flaviviruses (FVs) has broadened the transmission routes for ZIKV infection from vector-mediated to transmitted via body fluids. To further complicate the matters, it is genetically similar (about 40%) with the four serotypes of dengue virus (DENV), so much so that it can almost be called a fifth DENV serotype. This homology poses the risk of causing cross-reactive immune responses and subsequent antibody-dependent enhancement (ADE) of infection in case of secondary infections or for immunized individuals. All of these factors complicate the development of a single preventive vaccine candidate or a pharmacological intervention that will completely eliminate or cure ZIKV infection. We discuss all of these factors in detail in this review and conclude that a combinatorial approach including immunization and treatment might prove to be the winning strategy.

  6. Repeated Challenge with Virulent Newcastle Disease Virus Does Not Decrease the Efficacy of Vaccines.

    Science.gov (United States)

    Taylor, Tonya L; Miller, Patti J; Olivier, Timothy L; Montiel, Enrique; Cardenas Garcia, Stivalis; Dimitrov, Kiril M; Williams-Coplin, Dawn; Afonso, Claudio L

    2017-06-01

    Globally, poultry producers report that birds well-vaccinated for Newcastle disease (ND) often present clinical disease and mortality after infection with virulent strains of Newcastle disease (vNDV), which is contrary to what is observed in experimental settings. One hypothesis for this discrepancy is that the birds in the field may be exposed to multiple successive challenges with vNDV, rather than one challenge dose, and that the repeated infection may overwhelm the immune system and neutralizing antibodies available to prevent clinical disease. In this study, we evaluated this hypothesis under highly controlled conditions. We challenged well-vaccinated chickens with high doses of vNDV daily for 10 days, and looked for signs of clinical disease, changes in antibody titers, and mortality. All sham-vaccinated birds died by the fourth day postchallenge. No morbidity or mortality was observed in any of the NDV-vaccinated birds up to 14 days postchallenge; repeated high-dose challenges of vNDV was not sufficient to overcome vaccine immunity.

  7. Immunological Changes of Chicks Immunized with Marek‘s Disease Vaccines and Challenged with Virulent MD Virus

    Institute of Scientific and Technical Information of China (English)

    LiuZhonggui; GaoRong; 等

    1995-01-01

    The experiment was conducted to inoculate one-day old chicks with Marek's disecae(MD) trivalent and herpesvirus of turkey(HVT) vaccines separately,and then to challenge them with virulent MD virus(vMDV) at the age of 15 days,and 5,25,45,and 75 days after the challenge with vMDV,comparing with the cotrol-challenged chicks without immunization,to detect the immunoprotetive efficacy and dynamic changes of the inductive activity of interleukin-2(IL-2),expression of IL-2 receptor and proliferative function of T cells in thymus and spleen;the number of ANAET,APT,cells and IgG,IgM,IgA antibody-producing cells in Bursa Fabricius,spleen,thymus,cecal tonsil and Harder gland;as the amount of T cells and IgG,IgA in peripheral blood as well as the content of IgG,IgM and IgA in the tear,trachea washings,bile and intestinal fluids of the experimental chicks.The experimental results firstly demonstrate that the immunoregulation of IL-2,and IL-2 receptor,the cellualr and humoral immune resposes were significantly enhanced in the central and peripheral immune organs;the local mucosal immune funcsignificantly enhanced in the central and peripheral immune organs;the local mucosal immune function were markedly amplified in the respiratory and digestive tracts of the immunized-challenged,chicks,which were closely correlated with the immunoprotection against MD;the immune response and immunoprotective effect of the trivalent vaccine-immunized chicks wrer much better than those of HVT vaccine-immunized chicks.

  8. Protection Induced in Broiler Chickens following Drinking-Water Delivery of Live Infectious Laryngotracheitis Vaccines against Subsequent Challenge with Recombinant Field Virus.

    Science.gov (United States)

    Korsa, Mesula G; Browning, Glenn F; Coppo, Mauricio J C; Legione, Alistair R; Gilkerson, James R; Noormohammadi, Amir H; Vaz, Paola K; Lee, Sang-Won; Devlin, Joanne M; Hartley, Carol A

    2015-01-01

    Infectious laryngotracheitis virus (ILTV) causes acute upper respiratory tract disease in chickens. Attenuated live ILTV vaccines are often used to help control disease, but these vaccines have well documented limitations, including retention of residual virulence, incomplete protection, transmission of vaccine virus to unvaccinated birds and reversion to high levels of virulence following bird-to-bird passage. Recently, two novel ILTV field strains (class 8 and 9 ILTV viruses) emerged in Australia due to natural recombination between two genotypically distinct commercial ILTV vaccines. These recombinant field strains became dominant field strains in important poultry producing areas. In Victoria, Australia, the recombinant class 9 virus largely displaced the previously predominant class 2 ILTV strain. The ability of ILTV vaccines to protect against challenge with the novel class 9 ILTV strain has not been studied. Here, the protection induced by direct (drinking-water) and indirect (contact) exposure to four different ILTV vaccines against challenge with class 9 ILTV in commercial broilers was studied. The vaccines significantly reduced, but did not prevent, challenge virus replication in vaccinated chickens. Only one vaccine significantly reduced the severity of tracheal pathology after direct drinking-water vaccination. The results indicate that the current vaccines can be used to help control class 9 ILTV, but also indicate that these vaccines have limitations that should be considered when designing and implementing disease control programs.

  9. Early protection in sheep against intratypic heterologous challenge with serotype O foot-and-mouth disease virus using high-potency, emergency vaccine.

    Science.gov (United States)

    Horsington, Jacquelyn; Zhang, Zhidong; Bittner, Hilary; Hole, Kate; Singanallur, Nagendrakumar B; Alexandersen, Soren; Vosloo, Wilna

    2015-01-09

    In 2009-2011, spread of a serotype O foot-and-mouth disease virus (FMDV) belonging to the South East Asia topotype led to the culling of over 3.5 million cattle and pigs in Japan and Korea. The O1 Manisa vaccine (belonging to the Middle East-South Asian topotype) was used at high potency in Korea to limit the expansion of the outbreak. However, no data are available on the spread of this virus or the efficacy of the O1 Manisa vaccine against this virus in sheep. In this study, the early protection afforded with a high potency (>6 PD50) FMD O1 Manisa vaccine against challenge with the O/SKR/2010 virus was tested in sheep. Sheep (n=8) were vaccinated 4 days prior to continuous direct-contact challenge with donor sheep. Donor sheep were infected with FMDV O/SKR/2010 by coronary band inoculation 24h prior to contact with the vaccinated animals, or unvaccinated controls (n=4). Three of the four control sheep became infected, two clinically. All eight O1 Manisa vaccinated sheep were protected from clinical disease. None had detectable antibodies to FMDV non-structural proteins (3ABC), no virus was isolated from nasal swabs, saliva or oro-pharyngeal fluid and none became carriers. Using this model of challenge, sheep were protected against infection as early as 4 days post vaccination.

  10. HoBi-like virus challenge of pregnant cows that had previously given birth to calves persistently infected with bovine viral diarrhea virus

    Science.gov (United States)

    The ability of bovine viral diarrhea viruses (BVDV) to establish persistent infection (PI) following fetal infection is central to keeping these viruses circulating. Similarly, an emerging species of pestivirus, HoBi-like viruses, is also able to establish PIs. Dams that are not PI, but carrying PI ...

  11. Management of mother-to-child transmission of hepatitis B virus: Propositions and challenges.

    Science.gov (United States)

    Yi, Panpan; Chen, Ruochan; Huang, Yan; Zhou, Rong-Rong; Fan, Xue-Gong

    2016-04-01

    Chronic hepatitis B virus (HBV) infection due to mother-to-child transmission (MTCT) during perinatal period remains an important global health problem. Despite standard passive-active immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine in neonates, up to 9% of newborns still acquire HBV infection, especially these from hepatitis B e antigen (HBeAg) positive mothers. Management of HBV infection in pregnancy still need to draw careful attention because of some controversial aspects, including the failure of passive-active immunoprophylaxis in a fraction of newborns, the effect and necessity of periodical hepatitis B immunoglobulin (HBIG) injection to the mothers, the safety of antiviral prophylaxis with nucleoside/nucleotide analogs, the benefit of different delivery ways, and the safety of breastfeeding. In this review, we highlight these unsettled issues of preventive strategies in perinatal period, and we further aim to provide an optimal approach to the management of preventing MTCT of HBV infection.

  12. Hepatitis C virus whole genome sequencing: Current methods/issues and future challenges.

    Science.gov (United States)

    Trémeaux, Pauline; Caporossi, Alban; Thélu, Marie-Ange; Blum, Michael; Leroy, Vincent; Morand, Patrice; Larrat, Sylvie

    2016-10-01

    Therapy for hepatitis C is currently undergoing a revolution. The arrival of new antiviral agents targeting viral proteins reinforces the need for a better knowledge of the viral strains infecting each patient. Hepatitis C virus (HCV) whole genome sequencing provides essential information for precise typing, study of the viral natural history or identification of resistance-associated variants. First performed with Sanger sequencing, the arrival of next-generation sequencing (NGS) has simplified the technical process and provided more detailed data on the nature and evolution of viral quasi-species. We will review the different techniques used for HCV complete genome sequencing and their applications, both before and after the apparition of NGS. The progress brought by new and future technologies will also be discussed, as well as the remaining difficulties, largely due to the genomic variability.

  13. A baculovirus dual expression system-based vaccine confers complete protection against lethal challenge with H9N2 avian influenza virus in mice

    Directory of Open Access Journals (Sweden)

    Ye Yu

    2011-06-01

    Full Text Available Abstract Background Avian influenza viruses of H9N2 subtype have become highly prevalent in avian species. Although these viruses generally cause only mild to moderate disease, they can infect a wide variety of species, including chickens, quail, turkeys, ducks, geese, pheasant, partridge, and pigeon, even transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them. Results The results showed that stronger immune responses were induced in a mouse model immunized with BV-Dual-HA than in those vaccinated with a DNA vaccine encoding the same antigen. Moreover, complete protection against lethal challenge with H9N2 virus was observed in mice. Conclusion BV-Dual-HA could be utilized as a vaccine candidate against H9N2 virus infection.

  14. Rhizome of life, catastrophes, sequence exchanges, gene creations and giant viruses: How microbial genomics challenges Darwin

    OpenAIRE

    Vicky eMerhej; Didier eRaoult

    2012-01-01

    Darwin’s theory about the evolution of species has been the object of considerable dispute. In this review, we have described seven key principles in Darwin’s book The Origin of Species and tried to present how genomics challenge each of these concepts and improve our knowledge about evolution. Darwin believed that species evolution consists on a positive directional selection ensuring the survival of the fittest. The most developed state of the species is characterized by increasing complexi...

  15. Rhizome of life, catastrophes, sequence exchanges, gene creations, and giant viruses: how microbial genomics challenges Darwin

    OpenAIRE

    Merhej, Vicky; Raoult, Didier

    2012-01-01

    Darwin's theory about the evolution of species has been the object of considerable dispute. In this review, we have described seven key principles in Darwin's book The Origin of Species and tried to present how genomics challenge each of these concepts and improve our knowledge about evolution. Darwin believed that species evolution consists on a positive directional selection ensuring the “survival of the fittest.” The most developed state of the species is characterized by increasing comple...

  16. Immunoglobulin with High-Titer In Vitro Cross-Neutralizing Hepatitis C Virus Antibodies Passively Protects Chimpanzees from Homologous, but Not Heterologous, Challenge

    DEFF Research Database (Denmark)

    Bukh, Jens; Engle, Ronald E.; Faulk, Kristina;

    2015-01-01

    The importance of neutralizing antibodies (NAbs) in protection against hepatitis C virus (HCV) remains controversial. We infused a chimpanzee with H06 immunoglobulin from a genotype 1a HCV-infected patient and challenged with genotype strains efficiently neutralized by H06 in vitro. Genotype 1a N...

  17. Live virus immunization (LVI) with a recent 1-7-4 PRRSV isolate elicits broad protection against PRRSV challenge in finishing age swine

    Science.gov (United States)

    PRRSV infection is the most economically important disease affecting domestic swine herds in the United States and in many countries. Commercially available vaccines are often based on older viral strains and offer limited efficacy against heterologous challenge. Live virus immunization (LVI), a for...

  18. cDNA microarray analysis of disk abalone genes in gills and hemocytes after viral hemorrhagic septicemia virus (VHSV) challenge.

    Science.gov (United States)

    De Zoysa, Mahanama; Nikapitiya, Chamilani; Oh, Chulhong; Whang, Ilson; Shin, Hyun-Jin; Lee, Jehee

    2012-06-01

    A disk abalone Haliotis discus discus 4.2 K cDNA microarray was designed by selecting abalone expressed sequence tags (ESTs). Transcriptional profiles in gills and hemocytes were analyzed upon abalone challenged with viral hemorrhagic septicemia virus (VHSV) in order to select candidates for screening of immune response genes. Among the 4188 genes analyzed, 280 (6.6%) transcripts were changed their expression level in gills and hemocytes against VHSV challenge compared to control animals. Total of 88 and 65 genes were up-regulated in gills and hemocytes, respectively. These genes can be grouped under various immune-functional categories such as transcription factors (Krüppell-like factor; ETS-family transcription factor), inflammatory and apoptosis related genes (TNF superfamily members, Fas ligand), IFN regulatory proteins (IFN-44 like, interferon gamma-inducible lysosomal thiol reductase) and detoxification proteins (glutathione peroxidase). In contrast, 25 and 102 genes were shown down-regulation in gills and hemocytes, respectively. Among the differentially expressed transcripts, considerably higher numbers of ESTs were represented as either hypothetical (unknown) proteins or no GenBank match suggesting those may be novel genes associated with internal defense of abalone.

  19. Public health challenges and legacies of Japan's response to the Ebola virus disease outbreak in West Africa 2014 to 2015.

    Science.gov (United States)

    Saito, Tomoya

    2015-01-01

    The largest outbreak of Ebola virus disease occurred in West Africa in 2014 and resulted in unprecedented transmission even in distant countries. In Japan, only nine individuals were screened for Ebola and there was no confirmed case. However, the government promoted the reinforcement of response measures and interagency collaboration, with training and simulation exercises conducted country-wide. The legacies included: publication of a communication policy on case disclosure, a protocol for collaboration between public health and other agencies, and establishing an expert committee to assemble the limited available expertise. There were challenges in taking proportionate and flexible measures in the management of people identified to be at high risk at entry points to Japan, in the decentralised medical response strategy, and in the medical countermeasures preparedness. The Ebola outbreak in West Africa provided a crucial opportunity to reveal the challenges and improve the preparedness for rare but high impact emerging diseases that are prone to be neglected. Efforts to uphold the lessons learnt and maintain public health preparedness should help prepare for future emerging diseases, including bioterrorist acts and pandemics.

  20. Hepatitis A virus in the Middle East and North Africa region: a new challenge.

    Science.gov (United States)

    Melhem, N M; Talhouk, R; Rachidi, H; Ramia, S

    2014-01-01

    During the past three decades, a gradual shift in the age of infection with hepatitis A virus (HAV) from early childhood to adulthood has been observed. There is a general lack of updated data on HAV burden of disease, incidence and age-specific seroprevalence in countries of the Middle East and North Africa (MENA) region. The aim of this article is to review the published data on anti-HAV seroprevalence, an important tool to monitor infections rates, in countries of the MENA region and associated risk factors including water and socioeconomic data when available. Data on anti-HAV seroprevalence were found for 12 of 25 MENA countries. We show that MENA countries, similar to other areas in the world, have a clear shift in HAV incidence with a decline among young age groups and an increase among adults and older individuals. This would likely be associated with increased morbidity and increased risks of outbreaks among younger age groups. Consequently, the continuous surveillance of hepatitis A cases and the inclusion of hepatitis A vaccine in the expanded immunization programmes are needed in countries of the MENA.

  1. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.

    Directory of Open Access Journals (Sweden)

    Thomas R Hird

    Full Text Available Inactivated poliovirus vaccine (IPV may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24. In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11] or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]. There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

  2. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.

    Science.gov (United States)

    Hird, Thomas R; Grassly, Nicholas C

    2012-01-01

    Inactivated poliovirus vaccine (IPV) may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV) after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24)). In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11]) or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]). There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

  3. Fatal cases of Chikungunya virus infection in Colombia: Diagnostic and treatment challenges.

    Science.gov (United States)

    Hoz, Juan M de la; Bayona, Brayan; Viloria, Samir; Accini, José L; Juan-Vergara, Homero San; Viasus, Diego

    2015-08-01

    Although Chikungunya infection is emerging as an important public health problem in many countries, it is not regarded as a life-threatening disease. Information dealing with fatal cases is scarce. We herein describe three patients with Chickungunya infection who presented with multiple organ failure and died within 24h of admission. Two cases had positive anti-dengue IgM, but dengue coinfection was rejected based on the clinical features and results of real-time reverse transcription polymerase chain reaction. These cases illustrate the challenges of the diagnosis and management of severe Chikungunya infection.

  4. A Live Attenuated Equine Infectious Anemia Virus Proviral Vaccine with a Modified S2 Gene Provides Protection from Detectable Infection by Intravenous Virulent Virus Challenge of Experimentally Inoculated Horses

    Science.gov (United States)

    Li, Feng; Craigo, Jodi K.; Howe, Laryssa; Steckbeck, Jonathan D.; Cook, Sheila; Issel, Charles; Montelaro, Ronald C.

    2003-01-01

    Previous evaluations of inactivated whole-virus and envelope subunit vaccines to equine infectious anemia virus (EIAV) have revealed a broad spectrum of efficacy ranging from highly type-specific protection to severe enhancement of viral replication and disease in experimentally immunized equids. Among experimental animal lentivirus vaccines, immunizations with live attenuated viral strains have proven most effective, but the vaccine efficacy has been shown to be highly dependent on the nature and severity of the vaccine virus attenuation. We describe here for the first time the characterization of an experimental attenuated proviral vaccine, EIAVUKΔS2, based on inactivation of the S2 accessory gene to down regulate in vivo replication without affecting in vitro growth properties. The results of these studies demonstrated that immunization with EIAVUKΔS2 elicited mature virus-specific immune responses by 6 months and that this vaccine immunity provided protection from disease and detectable infection by intravenous challenge with a reference virulent biological clone, EIAVPV. This level of protection was observed in each of the six experimental horses challenged with the reference virulent EIAVPV by using a low-dose multiple-exposure protocol (three administrations of 10 median horse infectious doses [HID50], intravenous) designed to mimic field exposures and in all three experimentally immunized ponies challenged intravenously with a single inoculation of 3,000 HID50. In contrast, naïve equids subjected to the low- or high-dose challenge develop a detectable infection of challenge virus and acute disease within several weeks. Thus, these data demonstrate that the EIAV S2 gene provides an optimal site for modification to achieve the necessary balance between attenuation to suppress virulence and replication potential to sufficiently drive host immune responses to produce vaccine immunity to viral exposure. PMID:12805423

  5. Immunization of African Indigenous Pigs with Attenuated Genotype I African Swine Fever Virus OURT88/3 Induces Protection Against Challenge with Virulent Strains of Genotype I.

    Science.gov (United States)

    Mulumba-Mfumu, L K; Goatley, L C; Saegerman, C; Takamatsu, H-H; Dixon, L K

    2016-10-01

    The attenuated African swine fever virus genotype I strain OURT88/3 has previously been shown to induce protection of European breeds of domestic pigs against challenge with virulent isolates. To determine whether protective immune responses could also be induced in indigenous breeds of pigs from the Kinshassa region in Democratic Republic of Congo, we immunized a group of eight pigs with OURT88/3 strain and challenged the pigs 3 weeks later with virulent genotype I strain OURT88/1. Four of the pigs were protected against challenge. Three of the eight pigs died from African swine fever virus and a fourth from an unknown cause. The remaining four pigs all survived challenge with a recent virulent genotype I strain from the Democratic Republic of Congo, DRC 085/10. Control groups of non-immune pigs challenged with OURT88/1 or DRC 085/10 developed signs of acute ASFV as expected and had high levels of virus genome in blood.

  6. Differential RNAi responses of Nicotiana benthamiana individuals transformed with a hairpin-inducing construct during Plum pox virus challenge.

    Science.gov (United States)

    Montes, Christian; Castro, Álvaro; Barba, Paola; Rubio, Julia; Sánchez, Evelyn; Carvajal, Denisse; Aguirre, Carlos; Tapia, Eduardo; DelÍ Orto, Paola; Decroocq, Veronique; Prieto, Humberto

    2014-10-01

    Gene silencing and large-scale small RNA analysis can be used to develop RNA interference (RNAi)-based resistance strategies for Plum pox virus (PPV), a high impact disease of Prunus spp. In this study, a pPPViRNA hairpin-inducing vector harboring two silencing motif-rich regions of the PPV coat protein (CP) gene was evaluated in transgenic Nicotiana benthamiana (NB) plants. Wild-type NB plants infected with a chimeric PPV virus (PPV::GFP) exhibited affected leaves with mosaic chlorosis congruent to GFP fluorescence at 21 day post-inoculation; transgenic lines depicted a range of phenotypes from fully resistant to susceptible. ELISA values and GFP fluorescence intensities were used to select transgenic-resistant (TG-R) and transgenic-susceptible (TG-S) lines for further characterization of small interfering RNAs (siRNAs) by large-scale small RNA sequencing. In infected TG-S and untransformed (WT) plants, the observed siRNAs were nearly exclusively 21- and 22-nt siRNAs that targeted the whole PPV::GFP genome; 24-nt siRNAs were absent in these individuals. Challenged TG-R plants accumulated a full set of 21- to 24-nt siRNAs that were primarily associated with the selected motif-rich regions, indicating that a trans-acting siRNAs process prevented viral multiplication. BLAST analysis identified 13 common siRNA clusters targeting the CP gene. 21-nt siRNA sequences were associated with the 22-nt siRNAs and the scarce 23- and 24-nt molecules in TG-S plants and with most of the observed 22-, 23-, and 24-nt siRNAs in TG-R individuals. These results validate the use of a multi-hot spot silencing vector against PPV and elucidate the molecules by which hairpin-inducing vectors initiate RNAi in vivo.

  7. Prior infection of pigs with a genotype 3 swine hepatitis E virus (HEV) protects against subsequent challenges with homologous and heterologous genotypes 3 and 4 human HEV.

    Science.gov (United States)

    Sanford, Brenton J; Dryman, Barbara A; Huang, Yao-Wei; Feagins, Alicia R; Leroith, Tanya; Meng, Xiang-Jin

    2011-07-01

    Hepatitis E virus (HEV) is an important human pathogen. At least four recognized and two putative genotypes of mammalian HEV have been reported: genotypes 1 and 2 are restricted to humans whereas genotypes 3 and 4 are zoonotic. The current experimental vaccines are all based on a single strain of HEV, even though multiple genotypes of HEV are co-circulating in some countries and thus an individual may be exposed to more than one genotype. Genotypes 3 and 4 swine HEV is widespread in pigs and known to infect humans. Therefore, it is important to know if prior infection with a genotype 3 swine HEV will confer protective immunity against subsequent exposure to genotypes 3 and 4 human and swine HEV. In this study, specific-pathogen-free pigs were divided into 4 groups of 6 each. Pigs in the three treatment groups were each inoculated with a genotype 3 swine HEV, and 12 weeks later, challenged with the same genotype 3 swine HEV, a genotype 3 human HEV, and a genotype 4 human HEV, respectively. The control group was inoculated and challenged with PBS buffer. Weekly sera from all pigs were tested for HEV RNA and IgG anti-HEV, and weekly fecal samples were also tested for HEV RNA. The pigs inoculated with swine HEV became infected as evidenced by fecal virus shedding and viremia, and the majority of pigs also developed IgG anti-HEV prior to challenge at 12 weeks post-inoculation. After challenge, viremia was not detected and only two pigs challenged with swine HEV had 1-week fecal virus shedding, suggesting that prior infection with a genotype 3 swine HEV prevented pigs from developing viremia and fecal virus shedding after challenges with homologous and heterologous genotypes 3 and 4 HEV. The results from this study have important implications for future development of an effective HEV vaccine.

  8. A single immunization with HA DNA vaccine by electroporation induces early protection against H5N1 avian influenza virus challenge in mice

    Directory of Open Access Journals (Sweden)

    Chen Jianjun

    2009-02-01

    Full Text Available Abstract Background Developing vaccines for the prevention of human infection by H5N1 influenza viruses is an urgent task. DNA vaccines are a novel alternative to conventional vaccines and should contribute to the prophylaxis of emerging H5N1 virus. In this study, we assessed whether a single immunization with plasmid DNA expressing H5N1 hemagglutinin (HA could provide early protection against lethal challenge in a mouse model. Methods Mice were immunized once with HA DNA at 3, 5, 7 days before a lethal challenge. The survival rate, virus titer in the lungs and change of body weight were assayed to evaluate the protective abilities of the vaccine. To test the humoral immune response induced by HA DNA, serum samples were collected through the eye canthus of mice on various days after immunization and examined for specific antibodies by ELISA and an HI assay. Splenocytes were isolated after the immunization to determine the antigen-specific T-cell response by the ELISPOT assay. Results Challenge experiments revealed that a single immunization of H5N1 virus HA DNA is effective in early protection against lethal homologous virus. Immunological analysis showed that an antigen-specific antibody and T-cell response could be elicited in mice shortly after the immunization. The protective abilities were correlated with the amount of injected DNA and the length of time after vaccination. Conclusion A single immunization of 100 μg H5 HA DNA vaccine combined with electroporation was able to provide early protection in mice against homologous virus infection.

  9. Supplementation of inactivated influenza vaccine with norovirus P particle-M2e chimeric vaccine enhances protection against heterologous virus challenge in chickens

    Science.gov (United States)

    Elaish, Mohamed; Ali, Ahmed; Xia, Ming; Ibrahim, Mahmoud; Jang, Hyesun; Hiremath, Jagadish; Dhakal, Santosh; Helmy, Yosra A.; Jiang, Xi; Renukaradhya, Gourapura J.; Lee, Chang-Won

    2017-01-01

    The current inactivated influenza vaccines provide satisfactory protection against homologous viruses but limited cross-protection against antigenically divergent strains. Consequently, there is a need to develop more broadly protective vaccines. The highly conserved extracellular domain of the matrix protein 2 (M2e) has shown promising results as one of the components of a universal influenza vaccine in different animal models. As an approach to overcome the limited, strain specific, protective efficacy of inactivated influenza vaccine (IIV), a combination of recombinant M2e expressed on the surface of norovirus P particle (M2eP) and IIV was tested in chickens. Co-immunization of birds with both vaccines did not affect the production of M2e-specific IgG antibodies compared to the group vaccinated with M2eP alone. However, the co-immunized birds developed significantly higher pre-challenge hemagglutination inhibition antibody titers against the homologous IIV antigen and heterologous challenge virus. These combined vaccine groups also had cross reactive antibody responses against different viruses (H5, H6, and H7 subtypes) compared to the IIV alone vaccinated group. Upon intranasal challenge with homologous and heterologous viruses, the combined vaccine groups showed greater reduction in viral shedding in tracheal swabs compared to those groups receiving IIV alone. Moreover, M2eP antisera from vaccinated birds were able to bind to the native M2 expressed on the surface of whole virus particles and infected cells, and inhibit virus replication in vitro. Our results support the potential benefit of supplementing IIV with M2eP, to expand the vaccine cross protective efficacy. PMID:28151964

  10. Selection of reference genes for analysis of stress-responsive genes after challenge with viruses and temperature changes in the silkworm Bombyx mori.

    Science.gov (United States)

    Guo, Huizhen; Jiang, Liang; Xia, Qingyou

    2016-04-01

    Viruses and high temperature (HT) are the primary threats to silkworms. Changes in the expression of stress-response genes can be measured using quantitative polymerase chain reaction (qPCR) after exposure to viruses or HT. However, appropriate reference genes (RGs) for qPCR data normalization have not been established in this organism. In this study, we summarized the RGs used in the previous silkworm studies after infection with Bombyx mori nucleopolyhedrovirus (BmNPV), B. mori cytoplasmic polyhedrosis virus (BmCPV), or B. mori densovirus (BmDNV) or after HT treatment. The expression levels of these RGs were extracted from silkworm transcriptome data to screen for candidate RGs that were unaffected by the experimental conditions. Actin-1 (A1), actin-3 (A3), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and translation initiation factor 4a (TIF-4A) were selected for further qPCR verification. The results of RNA-seq and qPCR showed that GAPDH and TIF-4A were suitable RGs after BmNPV challenge or HT stress, whereas TIF-4A was an appropriate RG for BmCPV or BmDNV-Z challenge in silkworms. These results suggested that TIF-4A may be the most appropriate RG for gene expression analysis after challenge with viruses or HT in silkworms.

  11. Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models

    DEFF Research Database (Denmark)

    Bukh, Jens; Meuleman, Philip; Tellier, Raymond

    2010-01-01

    Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1-6 and determined the infectivity titer of acute-phase plasma pools in additional a...... resource for studies of HCV molecular virology and for studies of pathogenesis, protective immunity, and vaccine efficacy in vivo....... animals. The courses of first- and second-passage infections were similar, with early appearance of viremia, HCV RNA titers of >10(4.7) IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 10(3)-10(5) chimpanzee infectious doses/mL. Human liver......-chimeric mice developed high-titer infections after inoculation with the challenge viruses of genotypes 1-6. Inoculation studies with different doses of the genotype 1b pool suggested that a relatively high virus dose is required to consistently infect chimeric mice. The challenge pools represent a unique...

  12. Production of Monoclonal Antibodies Against the Challenge Strain of Infectious Laryngotracheitis Virus of Chickens and Their Use in an Indirect Immunofluorescent Diagnostic Test

    Directory of Open Access Journals (Sweden)

    Ferhat Abbas*, James Andreasen1, Rockey Becker1, Masroor Ahmed, M Arif Awan, Abdul Wadood and Anita Sonn1

    2010-07-01

    Full Text Available The objective of the present research was to produce monoclonal antibodies (MCAs against the USDA challenge strain of infectious laryngotracheitis virus and to perform an initial investigation of their use in an indirect immunofluorescence diagnostic test. Fourteen-day old chicken embryo liver cells were grown in tissue culture plates. Confluent monolayers were obtained after 48 hours. Monolayers were infected with the USDA challenge strain of infectious laryngotracheitis virus (ILTV. Cytopethic effect of the virus in the form of syncytial formation and clumping of cells was observed after 24 hours. The virus from the tissue culture flasks was collected and purified using discontinuous sucrose gradient. A clear band of the virus from sucrose gradient was obtained. The refractory index and the density measured were 1.410 and 1.20 g/cm3, respectively. Spectrophotometry of the purified virus showed 68.117 ug/ml of protein and 9.8948 ug/ml of nucleic acid concentration. Spleen cells from immunized mice with pure virus were fused with myeloma cells and hybridomas were obtained after 10 days. Screening was performed using indirect immunofluorescence antibody test (IFAT using rabbit anti-mouse immunoglobulins as secondary antibodies. Three hybridomas, 2D1D8, 2E11G2 and 2C6C7 were found producing antibodies against ILTV. All monoclonal antibodies were of isotype IgM and reacted with different strains of ILTV (ILTV USDA, S 88 00224, 86-1169 in IFAT. None of the monoclonals reacted with Parrot herpesvirus and avian adenovirus 301 in IFAT.

  13. Pre-exposing Canada Geese (Branta canadensis) to a low-pathogenic H1N1 avian influenza virus protects them against H5N1 HPAI virus challenge.

    Science.gov (United States)

    Berhane, Yohannes; Embury-Hyatt, Carissa; Leith, Marsha; Kehler, Helen; Suderman, Matthew; Pasick, John

    2014-01-01

    In previous studies we examined the role of Canada Geese (Branta canadensis) in the epidemiology of Eurasian highly pathogenic avian influenza (HPAI) H5N1. To expand on this and better understand how pre-exposure to heterosubtypic low-pathogenic avian influenza (LPAI) viruses might influence the outcome of H5N1 HPAI infection, we pre-exposed naïve juvenile Canada Geese to different North American wild-bird-origin LPAI viruses. We selected H1, H2, and H6 hemagglutinin subtype viruses based on their higher-order evolutionary relatedness to the H5 hemagglutinin. Pre-exposing Canada Geese to either H2N3 or H6N5 viruses did not protect them against a lethal H5N1 HPAI virus challenge. In addition, H5N1 was transmitted to naïve control birds that were placed among both groups resulting in death by 5 days postcontact. In contrast, Canada Geese that were pre-exposed to H1N1 were protected against a lethal H5N1 challenge, shed minimal amounts of the virus into the environment, and did not transmit the infection to naïve contact birds. None of the H1N1, H2N3, or H6N5 pre-exposure sera neutralized H5N1 in vitro; however, sera from H1N1-infected birds reduced virus plaque size but not number when compared with H2N3, H6N5, or negative sera, suggesting that antibodies directed against the neuraminidase may have had a role in the protective effects observed.

  14. Impact of route of exposure and challenge dose on the pathogenesis of H7N9 low pathogenicity avian influenza virus in chickens.

    Science.gov (United States)

    Spackman, Erica; Pantin-Jackwood, Mary; Swayne, David E; Suarez, David L; Kapczynski, Darrell R

    2015-03-01

    H7N9 influenza A first caused human infections in early 2013 in China. Virus genetics, histories of patient exposures to poultry, and previous experimental studies suggest the source of the virus is a domestic avian species, such as chickens. In order to better understand the ecology of this H7N9 in chickens, we evaluated the infectious dose and pathogenesis of A/Anhui/1/2013 H7N9 in two common breeds of chickens, White Leghorns (table-egg layers) and White Plymouth Rocks (meat chickens). No morbidity or mortality were observed with doses of 10(6) or 10(8)EID50/bird when administered by the upper-respiratory route, and the mean infectious dose (10(6) EID50) was higher than expected, suggesting that the virus is poorly adapted to chickens. Virus was shed at higher titers and spread to the kidneys in chickens inoculated by the intravenous route. Challenge experiments with three other human-origin H7N9 viruses showed a similar pattern of virus replication.

  15. Recombinant H7 hemagglutinin forms subviral particles that protect mice and ferrets from challenge with H7N9 influenza virus

    Science.gov (United States)

    Pushko, Peter; Pujanauski, Lindsey M.; Sun, Xiangjie; Pearce, Melissa; Hidajat, Rachmat; Kort, Thomas; Schwartzman, Louis M.; Tretyakova, Irina; Chunqing, Liu; Taubenberger, Jeffery K.; Tumpey, Terrence M.

    2015-01-01

    A novel avian-origin influenza A H7N9 virus emerged in China in 2013 and continues to cause sporadic human infections with mortality rates approaching 35%. Currently there are no approved human vaccines for H7N9 virus. Recombinant approaches including hemagglutinin (HA) and virus-like particles (VLPs) have resulted in experimental vaccines with advantageous safety and manufacturing characteristics. While high immunogenicity of VLP vaccines has been attributed to the native conformation of HA arranged in the regular repeated patterns within virus-like structures, there is limited data regarding molecular organization of HA within recombinant HA vaccine preparations. In this study, the full-length recombinant H7 protein (rH7) of A/Anhui/1/2013 (H7N9) virus was expressed in Sf9 cells. We showed that purified full-length rH7 retained functional ability to agglutinate red blood cells and formed oligomeric pleomorphic subviral particles (SVPs) of ~20 nm in diameter composed of approximately 10 HA0 molecules. No significant quantities of free monomeric HA0 were observed in rH7 preparation by size exclusion chromatography. Immunogenicity and protective efficacy of rH7 SVPs was confirmed in the mouse and ferret challenge models suggesting that SVPs can be used for vaccination against H7N9 virus. PMID:26207590

  16. Heterologous challenge with porcine reproductive and respiratory syndrome (PRRS) vaccine virus: no evidence of reactivation of previous European-type PRRS virus infection

    DEFF Research Database (Denmark)

    Bøtner, Anette; Nielsen, Jens; Oleksiewicz, M.B.

    1999-01-01

    In Denmark, a porcine reproductive and respiratory syndrome virus (PRRSV) control programme, comprising vaccination of seropositive herds with a live American type PRRSV vaccine, was started in 1996. In several of these herds, spread of vaccine virus from vaccinated 3-18 week old pigs to non-vacc...

  17. Rhizome of life, catastrophes, sequence exchanges, gene creations, and giant viruses: how microbial genomics challenges Darwin.

    Science.gov (United States)

    Merhej, Vicky; Raoult, Didier

    2012-01-01

    Darwin's theory about the evolution of species has been the object of considerable dispute. In this review, we have described seven key principles in Darwin's book The Origin of Species and tried to present how genomics challenge each of these concepts and improve our knowledge about evolution. Darwin believed that species evolution consists on a positive directional selection ensuring the "survival of the fittest." The most developed state of the species is characterized by increasing complexity. Darwin proposed the theory of "descent with modification" according to which all species evolve from a single common ancestor through a gradual process of small modification of their vertical inheritance. Finally, the process of evolution can be depicted in the form of a tree. However, microbial genomics showed that evolution is better described as the "biological changes over time." The mode of change is not unidirectional and does not necessarily favors advantageous mutations to increase fitness it is rather subject to random selection as a result of catastrophic stochastic processes. Complexity is not necessarily the completion of development: several complex organisms have gone extinct and many microbes including bacteria with intracellular lifestyle have streamlined highly effective genomes. Genomes evolve through large events of gene deletions, duplications, insertions, and genomes rearrangements rather than a gradual adaptative process. Genomes are dynamic and chimeric entities with gene repertoires that result from vertical and horizontal acquisitions as well as de novo gene creation. The chimeric character of microbial genomes excludes the possibility of finding a single common ancestor for all the genes recorded currently. Genomes are collections of genes with different evolutionary histories that cannot be represented by a single tree of life (TOL). A forest, a network or a rhizome of life may be more accurate to represent evolutionary relationships among

  18. Rhizome of life, catastrophes, sequence exchanges, gene creations and giant viruses: How microbial genomics challenges Darwin

    Directory of Open Access Journals (Sweden)

    Vicky eMerhej

    2012-08-01

    Full Text Available Darwin’s theory about the evolution of species has been the object of considerable dispute. In this review, we have described seven key principles in Darwin’s book The Origin of Species and tried to present how genomics challenge each of these concepts and improve our knowledge about evolution. Darwin believed that species evolution consists on a positive directional selection ensuring the survival of the fittest. The most developed state of the species is characterized by increasing complexity. Darwin proposed the theory of descent with modification according to which all species evolve from a single common ancestor through a gradual process of small modification of their vertical inheritance. Finally, the process of evolution can be depicted in the form of a tree. However, microbial genomics showed that evolution is better described as the biological changes over time." The mode of change is not unidirectional and does not necessarily favors advantageous mutations to increase fitness it is rather subject to random selection as a result of catastrophic stochastic processes. Complexity is not necessarily the completion of development: several complex organisms have gone extinct and many microbes including bacteria with intracellular lifestyle have streamlined highly effective genomes. Genomes evolve through large events of gene deletions, duplications, insertions and genomes rearrangements rather than a gradual adaptative process. Genomes are dynamic and chimeric entities with gene repertoires that result from vertical and horizontal acquisitions as well as de novo gene creation. The chimeric character of microbial genomes excludes the possibility of finding a single common ancestor for all the genes recorded currently. Genomes are collections of genes with different evolutionary histories that cannot be represented by a single tree of life. A forest, a network or a rhizome of life may be more accurate to represent evolutionary relationships

  19. MicroRNA and Hepatitis C Virus- Challenges in Investigation and Translation: A Review of the Literature

    Science.gov (United States)

    Waldron, Paul; Holodniy, Mark

    2015-01-01

    Investigations into the role of microRNA (miRNA) in hepatitis C virus (HCV) infection, disease pathogenesis and host immune and treatment response have potential to produce innovations in diagnosis, prognosis and therapy. However, investigational challenges remain in generating clinically useful and reproducible results. We review the literature with a primary emphasis on methods and technologies used to construct our current understanding of miRNA and HCV disease. A second emphasis is to understand potential clinical research applications and provide clarification of previous study results. Many miRNA have key roles in viral and immunopathogenesis of HCV infection across multiple tissue compartments. Controversy exists among published studies regarding relative measurements, temporal changes and biological significance of specific miRNA and HCV infection. To reconcile diverging data, additional research into optimal sample processing, in vitro models, techniques for microarray differential expression of miRNAs, practices for sample result normalization, and effect of HCV genotype variation on expression are all necessary. Microarray and miRNA isolation techniques should be selected based on ability to generate reproducible results in the sample type of interest. More direct comparisons of efficacy and reliability of various multiplex microarrays and an improved consensus around miRNA normalization and quantitation are necessary so that data can be compared across studies. PMID:24996839

  20. Bioinformatic characterization and gene expression pattern of apoptosis inhibitor from Macrobrachium rosenbergii challenged with infectious hypodermal and hematopoietic necrosis virus.

    Science.gov (United States)

    Arockiaraj, Jesu; Vanaraja, Puganeshwaran; Easwvaran, Sarasvathi; Singh, Arun; Othman, Rofina Yasmin; Bhassu, Subha

    2011-12-01

    Apoptosis is genetically programmed cellular killing processes that execute unnecessary or infected cells. It plays an important role in embryogenesis, homeostasis, insect metamorphosis and immunity. Apoptosis inhibitor (MrIAP) was sequenced from the freshwater giant prawn Macrobrachium rosenbergii using Illumina Solexa Genome Analyzer Technique. MrIAP consisted of 1753 base pair nucleotides encoded 535 polypeptide with an estimated molecular mass of 60 kDa. MrIAP amino acid sequence contains IAP superfamily domain between 5 and 490. The deduced amino acid sequences of the MrIAP were aligned with the other IAP family members. The highest sequence similarity was observed in IAP-5 from ant Camponotus floridanus (67%) followed by IAP from body louse Pediculus humanus corporis (66%) and the lowest (62%) in IAP-5 isoform-5 from common chimpanzee Pan troglodytes and IAP-5 from Aedes aegypti. The IAP phylogenetic tree showed that MrIAP closely related to other arthropod blacklegged tick Ixodes scapularis, formed a sister group with IAP from a hemichordate acorn worm Saccoglossus kowalevskii and finally clustered together with IAPs from fish groups. The quantitative real time PCR analysis revealed that significantly (P rosenbergii challenged to infectious hypodermal and hematopoietic necrosis virus (IHHNV) was highly induced in hepatopancreas. The collective results of this study indicate that the MrIAP is an essential immune gene and influences the immune response against IHHNV infection in M. rosenbergii.

  1. Sodium alginate from Sargassum wightii retards mortalities in Penaeus monodon postlarvae challenged with white spot syndrome virus.

    Science.gov (United States)

    Immanuel, Grasian; Sivagnanavelmurugan, Madasasmy; Balasubramanian, Varatharajan; Palavesam, Arunachalam

    2012-07-25

    Sodium alginate extracted from brown seaweed Sargassum wightii (16.35 ± 1.42%, mean [±SD] yield from 5 extractions) was prepared as a powder or beads and used to enrich Artemia nauplii at concentrations of 100, 200, 300 and 400 mg l-1. The alginate-enriched nauplii were fed to Penaeus monodon shrimp postlarvae (PL) stage 15 (PL15, i.e. 15 d old) for 20 d. Mean weight gain and specific growth rate over this period were 0.24 g and 15.8%, respectively, in PL groups not fed alginate, and 0.20-0.28 g and 14.7-16.5%, respectively, in PL groups fed alginate. Amongst PL35 then challenged with white spot syndrome virus (WSSV) by immersion, all PL not fed alginate died within 9 d. However, amongst PL fed the 4 concentrations of alginate powder or beads, mortality rates reduced with increasing alginate concentration, and between 25 and 32% PL remained alive when the bioassay was terminated on Day 21. Amongst alginate-fed PL groups compared with the control group, mortality was reduced by 26.5 to 58.4%. Nested PCR detection of WSSV revealed sodium alginate concentration-dependent reductions in infection loads. The data indicate that sodium alginate extracted from brown seaweed and fed to P. monodon can retard progression of WSSV disease.

  2. Chitosan can stop or postpone the death of the suckling mice challenged with foot-and-mouth disease virus

    Directory of Open Access Journals (Sweden)

    Li Dong

    2010-06-01

    Full Text Available Abstract In the study, a method called "hardening in liquid phase" for preparing chitosan granules with glutaraldehyde as crosslinker and Tween 80 as surfactant and paraffin liquid as dispersant was established. The chitosan granules were light yellow and insoluble in water or oil, but they swelled in acid solution and narrowed in neutral or alkaline solution. Furthermore, some of characteristics of the chitosan granules were revealed. (a Stability: Their shapes were stable at pH 7.0 and pH 8.0 and -30°C~120°C. The shelf life is at least one year in vitro at room temperature. (b Safety: Some experiments of their lethal effect to suckling mice and pathogenicity to mature mice proved the chitosan granules were harmless. (c Antiviral activity: Some suckling mice injected with chitosan granules were still alive or delayed death compared with control group when they challenged with foot-and-mouth disease virus (FMDV. Such anti-FMDV capacity could maintain 1 week and was the strongest on the third day.

  3. An adjuvanted, tetravalent dengue virus purified inactivated vaccine candidate induces long-lasting and protective antibody responses against dengue challenge in rhesus macaques.

    Science.gov (United States)

    Fernandez, Stefan; Thomas, Stephen J; De La Barrera, Rafael; Im-Erbsin, Rawiwan; Jarman, Richard G; Baras, Benoît; Toussaint, Jean-François; Mossman, Sally; Innis, Bruce L; Schmidt, Alexander; Malice, Marie-Pierre; Festraets, Pascale; Warter, Lucile; Putnak, J Robert; Eckels, Kenneth H

    2015-04-01

    The immunogenicity and protective efficacy of a candidate tetravalent dengue virus purified inactivated vaccine (TDENV PIV) formulated with alum or an Adjuvant System (AS01, AS03 tested at three different dose levels, or AS04) was evaluated in a 0, 1-month vaccination schedule in rhesus macaques. One month after dose 2, all adjuvanted formulations elicited robust and persisting neutralizing antibody titers against all four dengue virus serotypes. Most of the formulations tested prevented viremia after challenge, with the dengue serotype 1 and 2 virus strains administered at 40 and 32 weeks post-dose 2, respectively. This study shows that inactivated dengue vaccines, when formulated with alum or an Adjuvant System, are candidates for further development.

  4. Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge

    Directory of Open Access Journals (Sweden)

    Roberts Paul C

    2009-04-01

    Full Text Available Abstract Background Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1, demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC. Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine. Results We have evaluated the immunogenicity of inactivated cytokine-bearing influenza vaccines using a mouse model of lethal influenza virus challenge. CYT-IVACs were produced by stably transfecting MDCK cell lines with mouse-derived cytokines (GM-CSF, IL-2 and IL-4 fused to the membrane-anchoring domain of the viral hemagglutinin. Influenza virus replication in these cell lines resulted in the uptake of the bioactive membrane-bound cytokines during virus budding and release. In vivo efficacy studies revealed that a single low dose of IL-2 or IL-4-bearing CYT-IVAC is superior at providing protection against lethal influenza challenge in a mouse model and provides a more balanced Th1/Th2 humoral immune response, similar to live virus infections. Conclusion We have validated the protective efficacy of CYT-IVACs in a mammalian model of influenza virus infection. This technology has broad applications in current influenza virus vaccine development and may prove particularly useful in boosting immune responses in the elderly, where current vaccines are minimally effective.

  5. Comparison of protection provided by type 1 and type 2 porcine reproductive and respiratory syndrome field viruses against homologous and heterologous challenge.

    Science.gov (United States)

    Choi, Kyuhyung; Park, Changhoon; Jeong, Jiwoon; Chae, Chanhee

    2016-08-15

    The objective of this study was to compare protection provided by type 1 and type 2 porcine reproductive and respiratory syndrome virus (PRRSV) against homologous and heterologous challenge based on clinical, virological, immunological, and pathological analysis. At 3 and 8 weeks of age, pigs were inoculated intranasally with either 3mL of tissue culture fluid containing 10(5) TCID50/mL of type 1 PRRSV or 3mL of tissue culture fluid containing 10(5) TCID50/mL of type 2 PRRSV. The homologous challenges resulted in a significant boost of the neutralizing antibodies (NA) and interferon-γ secreting cells (IFN-γ-SC) compared to heterologous challenges. The reduction of secondary challenging PRRSV viremia coincided with the appearance of homologous PRRSV-specific NA and IFN-γ-SC. Homologous challenge reduced the severity of lung lesions and levels of PRRSV viremia significantly in pigs in comparison with heterologous challenge. The differences in homologous and heterologous NA and IFN-γ-SC response may explain the differences in protection against homologous and heterologous challenge between type 1 and type 2 PRRSV. Primary challenge (immunization) with type 1 PRRSV provided protection against the secondary homologous challenge with type 1 PRRSV but failed to provide protection against the secondary heterologous challenge of type 2 PRRSV. Primary challenge with type 2 PRRSV provided protection against both the secondary homologous challenge with type 2 PRRSV and the secondary heterologous challenge with type 1 PRRSV. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. An interferon inducing porcine reproductive and respiratory syndrome virus vaccine candidate elicits protection against challenge with the heterologous virulent type 2 strain VR-2385 in pigs.

    Science.gov (United States)

    Fontanella, Eve; Ma, Zexu; Zhang, Yanjin; de Castro, Alessandra M M G; Shen, Huigang; Halbur, Patrick G; Opriessnig, Tanja

    2017-01-03

    Achieving consistent protection by vaccinating pigs against porcine reproductive and respiratory syndrome virus (PRRSV) remains difficult. Recently, an interferon-inducing PRRSV vaccine candidate strain A2MC2 was demonstrated to be attenuated and induced neutralizing antibodies. The objective of this study was to determine the efficacy of passage 90 of A2MC2 (A2P90) to protect pigs against challenge with moderately virulent PRRSV strain VR-2385 (92.3% nucleic acid identity with A2MC2) and highly virulent atypical PRRSV MN184 (84.5% nucleic acid identity with A2MC2). Forty 3-week old pigs were randomly assigned to five groups including a NEG-CONTROL group (non-vaccinated, non-challenged), VAC-VR2385 (vaccinated, challenged with strain VR-2385), VR2385 (challenged with strain VR-2385), VAC-MN184 (vaccinated, challenged with strain MN184) and a MN184 group (challenged with MN184 virus). Vaccination was done at 3weeks of age followed by challenge at 8weeks of age. No viremia was detectable in any of the vaccinated pigs; however, by the time of challenge, 15/16 vaccinated pigs had seroconverted based on ELISA and had neutralizing antibodies against a homologous strain with titers ranging from 8 to 128. Infection with VR-2385 resulted in mild-to-moderate clinical disease and lesions. For VR-2385 infected pigs, vaccination significantly lowered PRRSV viremia and nasal shedding by 9days post challenge (dpc), significantly reduced macroscopic lung lesions, and significantly increased the average daily weight gain compared to the non-vaccinated pigs. Infection with MN184 resulted in moderate-to-severe clinical disease and lesions regardless of vaccination status; however, vaccinated pigs had significantly less nasal shedding by dpc 5 compared to non-vaccinated pigs. Under the study conditions, the A2P90 vaccine strain was attenuated without detectable shedding, improved weight gain, and offered protection to the pigs challenged with VR-2385 by reduction of virus load and

  7. Profound protection against respiratory challenge with a lethal H7N7 influenza A virus by increasing the magnitude of CD8(+) T-cell memory

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Doherty, P C; Branum, K C

    2000-01-01

    greatly increased subsequent to the H7N7 challenge, and though lung titers remained as high as those in naive controls for 5 days or more, the virus was cleared more rapidly. Expanding the CD8(+) memory T-cell pool (10%) by sequential priming with two different influenza A viruses (H3N2-->H1N1......The recall of CD8(+) T-cell memory established by infecting H-2(b) mice with an H1N1 influenza A virus provided a measure of protection against an extremely virulent H7N7 virus. The numbers of CD8(+) effector and memory T cells specific for the shared, immunodominant D(b)NP(366) epitope were...... for T-cell extravasation. The selective induction of CD8(+) T-cell memory can thus greatly limit the damage caused by a virulent influenza A virus, with the extent of protection being directly related to the number of available responders. Furthermore, a large pool of CD8(+) memory T cells may be only...

  8. Detection of Ebola Virus RNA through Aerosol Sampling of Animal Biosafety Level 4 Rooms Housing Challenged Nonhuman Primates

    Science.gov (United States)

    2016-08-02

    301- 619-4768(f). 1 2 3 4 5 6 7 8 Title: Detection of Ebola Virus RNA through Aerosol Sampling of Animal Biosafety Level 9 4...embedded in the texts. This is the first report demonstrating detection of Ebola virus 17 RNA from animal rooms housing infected nonhuman primates and...on Ebola virus disease and NHP animal models 34 of filovirus infections 35 • Dr. Robert Hawley, Private Consultant, bobhawley226@gmail.com, Former

  9. DNA Vaccination of the American Crow (Corvus brachyrhynchos) Provides Partial Protection Against Lethal Challenge with West Nile Virus

    Science.gov (United States)

    2007-01-01

    protección parcial contra el desafı́o letal con el virus del Oeste del Nilo. La cepa del virus del Oeste del Nilo aislada en Nueva York en el año 1999 es...murieron. La administración parenteral de la vacuna de ADN del virus del Oeste del Nilo estuvo asociada con una reducción de la mortalidad pero no

  10. Dual effects of respiratory syncytial virus infections on airway inflammation by regulation of Th17/Treg responses in ovalbumin-challenged mice.

    Science.gov (United States)

    Wang, Jia; Kong, Lingwen; Luo, Qingli; Li, Bei; Wu, Jinfeng; Liu, Baojun; Wu, Xiao; Dong, Jingcheng

    2014-12-01

    We investigated the effects of respiratory syncytial virus (RSV) infections on ovalbumin (OVA)-challenged mice via regulation of Th17/Treg cell responses. BALB/c mice were challenged with OVA, followed by RSV infections twice. In OVA-challenged mice, the secretion of Th2/Th17-type cytokines, airway hyperresponsiveness and inflammation were significantly inhibited by initial RSV infection. Moreover, the in vivo findings demonstrated that initial RSV infection reversed the imbalance of Th17/Treg responses. In contrast, RSV re-infection strengthened Th2/Th17-type cytokine secretion, airway hyperresponsiveness, and inflammation, especially for lymphocyte infiltration in OVA-challenged mice. Meanwhile, RSV re-infection enhanced the imbalanced Th17/Treg responses. Upon all results reveal that RSV-induced respiratory infections may lead to dual effects pertaining to allergic airway inflammation by regulation of Th17/Treg responses.

  11. Kyasanur forest disease virus: viremia and challenge studies in monkeys with evidence of cross-protection by Langat virus infection [v1; ref status: indexed, http://f1000r.es/UiWGcy

    Directory of Open Access Journals (Sweden)

    Keerti V Shah

    2012-12-01

    Full Text Available Kyasanur Forest Disease Virus (KFDV, discovered in 1957, is a member of the tick-borne encephalitis virus (TBEV complex. Diseases caused by members of the TBEV complex occur in many parts of the world. KFDV produces a hemorrhagic fever in humans in South India and fatal illnesses in both species of monkeys in the area, the black faced langur (Presbytis entellus and the bonnet macaque (Macaca radiata. Experimental infection of the langur and the bonnet macaque with early mouse passage KFDV strain P9605 resulted in a viremia of up to 11 days duration, peak viremia titers as high as 109, and death in 82 = 100% of the animals. Prolonged passage of the KFDV strain P9605 in monkey kidney tissue culture resulted in a markedly reduced virulence of the virus for both species; peak viremia titers in monkeys decreased by 2.5 to 4.0 log LD 50 (p= 0.001, and the mortality decreased to 10% (p= 0.001. In challenge experiments, monkeys previously infected with tissue-culture-adapted KFDV, or with the related Langat virus from Malaysia, were fully protected against virulent KFDV. These studies in non-human primates lend support to the idea that a live virus vaccine from a member of the TBEV complex may be broadly protective against infections by other members of the TBEV complex.

  12. Comparison of Host Immune Responses to Homologous and Heterologous Type II Porcine Reproductive and Respiratory Syndrome Virus (PRRSV Challenge in Vaccinated and Unvaccinated Pigs

    Directory of Open Access Journals (Sweden)

    X. Li

    2014-01-01

    Full Text Available Porcine reproductive and respiratory syndrome (PRRS is a high-consequence animal disease with current vaccines providing limited protection from infection due to the high degree of genetic variation of field PRRS virus. Therefore, understanding host immune responses elicited by different PRRSV strains will facilitate the development of more effective vaccines. Using IngelVac modified live PRRSV vaccine (MLV, its parental strain VR-2332, and the heterologous KS-06-72109 strain (a Kansas isolate of PRRSV, we compared immune responses induced by vaccination and/or PRRSV infection. Our results showed that MLV can provide complete protection from homologous virus (VR-2332 and partial protection from heterologous (KS-06 challenge. The protection was associated with the levels of PRRSV neutralizing antibodies at the time of challenge, with vaccinated pigs having higher titers to VR-2332 compared to KS-06 strain. Challenge strain did not alter the cytokine expression profiles in the serum of vaccinated pigs or subpopulations of T cells. However, higher frequencies of IFN-γ-secreting PBMCs were generated from pigs challenged with heterologous PRRSV in a recall response when PBMCs were re-stimulated with PRRSV. Thus, this study indicates that serum neutralizing antibody titers are associated with PRRSV vaccination-induced protection against homologous and heterologous challenge.

  13. A cytomegalovirus-based vaccine provides long-lasting protection against lethal Ebola virus challenge after a single dose.

    Science.gov (United States)

    Tsuda, Yoshimi; Parkins, Christopher J; Caposio, Patrizia; Feldmann, Friederike; Botto, Sara; Ball, Susan; Messaoudi, Ilhem; Cicin-Sain, Luka; Feldmann, Heinz; Jarvis, Michael A

    2015-05-01

    Ebola virus (Zaire ebolavirus; EBOV) is a highly lethal hemorrhagic disease virus that most recently was responsible for two independent 2014 outbreaks in multiple countries in Western Africa, and the Democratic Republic of the Congo, respectively. Herein, we show that a cytomegalovirus (CMV)-based vaccine provides durable protective immunity from Ebola virus following a single vaccine dose. This study has implications for human vaccination against ebolaviruses, as well as for development of a 'disseminating' vaccine to target these viruses in wild African great apes.

  14. Comparación antigénica y de la respuesta inmune en ratones desafiados con virus CVS y aislados «calle» y «fijo»presumiblemente atípicos del virus rábico Antigenic comparison and immune response in challenges mice with virus CVS and "street" and "fixed" isolates presumably atipics of rabies virus

    Directory of Open Access Journals (Sweden)

    P. MARTINEZ

    1999-01-01

    Full Text Available El virus de la rabia presenta diferencias antigénicas que han sido detectadas en diferentes regiones y países, lo que podría acarrear un serio problema en relación a las vacunas antirrábicas empleadas en terreno que no se corresponden con las cepas actuantes pudiendo provocar fracaso del tratamiento vacunal preventivo o post-exposición. Ante la sospecha de la existencia de virus rabia presuntamente atípicos en nuestro país, nos planteamos como objetivo estudiar el comportamiento antigénico de aislados vírales "calle" y "fijo" en relación a la cepa estándar, Challenge Virus Standar, frente a las vacunas antirrábicas veterinaria y de referencia nacional, y el suero antirrábico hiperinmune de referencia nacional. Se estudiaron 6 aislados de virus rábico presuntamente atípicos (5 de murciélagos y 1 de gato obtenidos en 1985 en el Instituto de Salud Pública y mantenidos a -70ºC en cerebro de ratón lactante. Para ello, primeramente, con la finalidad de lograr la fijación de los aislados a los animales de laboratorio, se procedió a realizar pasajes sucesivos en CRL, confirmando en cada pasaje la causa de muerte a través de la prueba de inmunofluorescencia directa. Para determinar la protección conferida en ratones, por las vacunas tradicionales frente a los aislados presuntamente atípicos, se compararon las respuestas de ratones vacunados y desafiados con los 6 aislados en su forma "calle" y "fija", con las respuestas de los ratones vacunados y desafiados con la cepa de referencia del virus estándar de desafío CVS. Para conocer la capacidad de neutralización del suero de referencia nacional frente a los aislados vírales "fijo", se compararon los resultados de neutralización en ratones, de cada uno de los aislados enfrentados al suero de referencia nacional, con la neutralización de la cepa CVS enfrentada al mismo suero. La fijación se logró en el pasaje Nº 16, para los aislados 85/423, 85/433, 85/684, 85/882, 85

  15. Comparison of the efficacy of autogenous inactivated Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) vaccines with that of commercial vaccines against homologous and heterologous challenges.

    Science.gov (United States)

    Geldhof, Marc F; Vanhee, Merijn; Van Breedam, Wander; Van Doorsselaere, Jan; Karniychuk, Uladzimir U; Nauwynck, Hans J

    2012-10-03

    The porcine reproductive and respiratory syndrome virus (PRRSV) is a rapidly evolving pathogen of swine. At present, there is a high demand for safe and more effective vaccines that can be adapted regularly to emerging virus variants. A recent study showed that, by the use of a controlled inactivation procedure, an experimental BEI-inactivated PRRSV vaccine can be developed that offers partial protection against homologous challenge with the prototype strain LV. At present, it is however not known if this vaccine can be adapted to currently circulating virus variants. In this study, two recent PRRSV field isolates (07 V063 and 08 V194) were used for BEI-inactivated vaccine production. The main objective of this study was to assess the efficacy of these experimental BEI-inactivated vaccines against homologous and heterologous challenge and to compare it with an experimental LV-based BEI-inactivated vaccine and commercial inactivated and attenuated vaccines. In addition, the induction of challenge virus-specific (neutralizing) antibodies by the different vaccines was assessed. In a first experiment (challenge with 07 V063), vaccination with the experimental homologous (07 V063) inactivated vaccine shortened the viremic phase upon challenge with approximately 2 weeks compared to the mock-vaccinated control group. Vaccination with the commercial attenuated vaccines reduced the duration of viremia with approximately one week compared to the mock-vaccinated control group. In contrast, the experimental heterologous (LV) inactivated vaccine and the commercial inactivated vaccine did not influence viremia. Interestingly, both the homologous and the heterologous experimental inactivated vaccine induced 07 V063-specific neutralizing antibodies upon vaccination, while the commercial inactivated and attenuated vaccines failed to do so.In the second experiment (challenge with 08 V194), use of the experimental homologous (08 V194) inactivated vaccine shortened viremia upon

  16. Transcriptome analysis of hemocytes and hepatopancreas in red swamp crayfish, Procambarus clarkii, challenged with white spot syndrome virus

    Directory of Open Access Journals (Sweden)

    X-Z Shi

    2010-04-01

    Full Text Available Red swamp crayfish Procambarus clarkii is used for the innate immune defense of crustaceans due to its convenience for laboratory culture and study. To know more about the transcriptome of the crayfish, we constructed and sequenced a cDNA library from a mixture of hemocytes and hepatopancreas from white spot syndrome virus (WSSV-infected crayfish. By random sequencing, we obtained 9115 high-quality expressed sequence tags with a mean length of 370 bp, representing 3033 unigenes. Most of the unigenes are first reports for the red swamp crayfish. Besides the metabolic genes, many genes that may be involved in the innate immune system of the crayfish are also obtained from the library, such as antimicrobial peptides, pattern recognition receptors, proteases and protease inhibitors, signal transduction proteins, apoptosis-, antioxidant-, and RNA interference-related proteins. We chose ten immune-related genes to analyze their expression pattern by quantitative real time polymerase chain reaction (qRT-PCR from the hemocytes of normal and WSSV-challenged crayfish. Seven of them, including anti-lipopolysaccharide factor, astacidin, crustin 1, H3 histone family 3A, serine/threonine protein kinase, TGF beta-inducible nuclear protein, and tar RNA binding protein, were upregulated after WSSV injection, but the mRNA expression levels of crustin 2, a lectin, and a digestive cysteine protease decreased after WSSV infection. Our results showed that the transcriptome analysis provides a useful resource for identification of immune related genes and understanding the immune responses of the crayfish.

  17. Intranasal vaccination with a plant-derived H5 HA vaccine protects mice and ferrets against highly pathogenic avian influenza virus challenge.

    Science.gov (United States)

    Major, Diane; Chichester, Jessica A; Pathirana, Rishi D; Guilfoyle, Kate; Shoji, Yoko; Guzman, Carlos A; Yusibov, Vidadi; Cox, Rebecca J

    2015-01-01

    Highly pathogenic avian influenza H5N1 infection remains a public health threat and vaccination is the best measure of limiting the impact of a potential pandemic. Mucosal vaccines have the advantage of eliciting immune responses at the site of viral entry, thereby preventing infection as well as further viral transmission. In this study, we assessed the protective efficacy of hemagglutinin (HA) from the A/Indonesia/05/05 (H5N1) strain of influenza virus that was produced by transient expression in plants. The plant-derived vaccine, in combination with the mucosal adjuvant (3',5')-cyclic dimeric guanylic acid (c-di-GMP) was used for intranasal immunization of mice and ferrets, before challenge with a lethal dose of the A/Indonesia/05/05 (H5N1) virus. Mice vaccinated with 15 μg or 5 μg of adjuvanted HA survived the viral challenge, while all control mice died within 10 d of challenge. Vaccinated animals elicited serum hemagglutination inhibition, IgG and IgA antibody titers. In the ferret challenge study, all animals vaccinated with the adjuvanted plant vaccine survived the lethal viral challenge, while 50% of the control animals died. In both the mouse and ferret models, the vaccinated animals were better protected from weight loss and body temperature changes associated with H5N1 infection compared with the non-vaccinated controls. Furthermore, the systemic spread of the virus was lower in the vaccinated animals compared with the controls. Results presented here suggest that the plant-produced HA-based influenza vaccine adjuvanted with c-di-GMP is a promising vaccine/adjuvant combination for the development of new mucosal influenza vaccines.

  18. A recombinant Rift Valley fever virus glycoprotein subunit vaccine confers full protection against Rift Valley fever challenge in sheep

    Science.gov (United States)

    Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease outbreaks in Africa and the Arabian Peninsula. The virus has great potential for transboundary spread due to the presence of competent vectors in non-endemic areas. There is currently no fully licensed vaccine suita...

  19. Differential expression of miRNA-423-5p in serum from cattle challenged with bovine viral diarrhea virus

    Science.gov (United States)

    Bovine viral diarrhea virus (BVDV) is an RNA virus that causes respiratory disease in cattle. MicroRNAs have been proposed as indicators of exposure to respiratory pathogens. However, microRNA profiles in cattle exposed to BVDV are currently nonexistent and few studies have been reported; therefore,...

  20. Vaccination with experimental feline immunodeficiency virus vaccines, based on autologous infected cells, elicits enhancement of homologous challenge infection.

    NARCIS (Netherlands)

    J.A. Karlas (Jos); C.H.J. Siebelink (Kees); M.A. van Peer (Maartje); W. Huisman (Willem); A.M. Cuisinier; G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

    1999-01-01

    textabstractCats were vaccinated with fixed autologous feline immunodeficiency virus (FIV)-infected cells in order to present viral proteins to the immune system of individual cats in an MHC-matched fashion. Upon vaccination, a humoral response against Gag was induced. Furthermore, virus-neutralizin

  1. Protective efficacy of an H5N1 DNA vaccine against challenge with a lethal H5N1 virus in quail.

    Science.gov (United States)

    Li, Junping; Jiang, Yongping; Zhao, Shuangcheng; Chang, Xiaofei; Liu, Jinxiong; Zeng, Xianying; Li, Yanbing; Chen, Hualan

    2012-12-01

    Some H5N1 avian influenza viruses (AIVs) are lethal to quail; however, the use of inactivated vaccines in these birds is largely restricted because of side effects caused by oil adjuvants. Here we evaluated the protective efficacy of a DNA vaccine against lethal challenge with H5N1 highly pathogenic avian influenza virus (HPAIV) in quail. Groups of ten 3-wk-old quail were intramuscularly inoculated three times at 3-wk intervals with 10, 15, 30, or 60 microg, respectively, of plasmid pCAGGoptiHA, which expresses a codon-optimized hemagglutinin gene of the H5N1 virus A/goose/Guangdong/1/96 (GS/GD/96). The control group was inoculated with phosphate-buffered saline. Hemagglutination-inhibition (HI) antibodies were monitored every week after the primary vaccination. The quail were challenged intranasally with 10(5) EID50 of heterologous HPAIV A/duck/Fujian/31/2007 (DK/ FJ/31) (H5N1) 2 wk after the third inoculation. Oropharyngeal and cloacal swab specimens were collected 3, 5, and 7 days after inoculation, and quail were observed daily for disease signs and death for 2 wk. The quail showed no side effects after the plasmid inoculation, and HI antibodies were detectable 1 wk after the second vaccination in all groups and increased sharply after the third inoculation. All quail in the PBS-inoculated group and 20% of the birds in the 10 microg plasmid-inoculated group died after the lethal H5N1 virus challenge; however, birds in the 15, 30, and 60 jg plasmid-inoculated groups were completely protected. These results indicate that this DNA vaccine holds promise for use in quail to protect against H5N1 AIV.

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

    Directory of Open Access Journals (Sweden)

    John M. Dye

    2016-04-01

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

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

    Science.gov (United States)

    Dye, John M; Warfield, Kelly L; Wells, Jay B; Unfer, Robert C; Shulenin, Sergey; Vu, Hong; Nichols, Donald K; Aman, M Javad; Bavari, Sina

    2016-04-08

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

  4. Comparison of protein expression profiles of the hepatopancreas in Fenneropenaeus chinensis challenged with heat-inactivated Vibrio anguillarum and white spot syndrome virus.

    Science.gov (United States)

    Jiang, Hao; Li, Fuhua; Zhang, Jiquan; Zhang, Jinkang; Huang, Bingxin; Yu, Yang; Xiang, Jianhai

    2014-02-01

    Fenneropenaeus chinensis (Chinese shrimp) culture industry, like other Penaeidae culture, has been seriously affected by the shrimp diseases caused by bacteria and virus. To better understand the mechanism of immune response of shrimp to different pathogens, proteome research approach was utilized in this study. Firstly, the soluble hepatopancreas protein samples in adult Chinese shrimp among control, heat-inactivated Vibrio-challenged and white spot syndrome virus-infected groups were separated by 2-DE (pH range, 4-7; sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and pH range, 3-10; tricine-SDS-PAGE). Then the differentially expressed protein spots (≥1.5-fold or ≤0.67-fold averagely of controls) were analyzed by LC-ESI-MS/MS. Using Mascot online database searching algorithm and SEQUEST searching program, 48 and 49 differentially expressed protein spots were successfully identified in response to Vibrio and white spot syndrome virus infection, respectively. Based on these results, we discussed the mechanism of immune response of the shrimp and shed light on the differences between immune response of shrimp toward Vibrio and white spot syndrome virus. This study also set a basis for further analyses of some key genes in immune response of Chinese shrimp.

  5. An equine herpesvirus 1 (EHV-1) vectored H1 vaccine protects against challenge with swine-origin influenza virus H1N1.

    Science.gov (United States)

    Said, Abdelrahman; Damiani, Armando; Ma, Guanggang; Kalthoff, Donata; Beer, Martin; Osterrieder, Nikolaus

    2011-12-29

    In 2009, a novel swine-origin H1N1 influenza A virus (S-OIV), antigenically and genetically divergent from seasonal H1N1, caused a flu pandemic in humans. Development of an effective vaccine to limit transmission of S-OIV in animal reservoir hosts and from reservoir hosts to humans and animals is necessary. In the present study, we constructed and evaluated a vectored vaccine expressing the H1 hemagglutinin of a recent S-OIV isolate using equine herpesvirus 1 (EHV-1) as the delivery vehicle. Expression of the recombinant protein was demonstrated by immunofluorescence and western blotting and the in vitro growth properties of the modified live vector were found to be comparable to those of the parental virus. The EHV-1-H1 vaccine induced an influenza virus-specific antibody response when inoculated into mice by both the intranasal and subcutaneous routes. Upon challenge infection, protection of vaccinated mice could be demonstrated by reduction of clinical signs and faster virus clearance. Our study shows that an EHV-1-based influenza H1N1 vaccine may be a promising alternative for protection against S-OIV infection.

  6. Examination of virus shedding in semen from vaccinated and from previously infected boars after experimental challenge with porcine reproductive and respiratory syndrome virus

    DEFF Research Database (Denmark)

    Nielsen, Thomas L.; Nielsen, Jens; Have, Per;

    1997-01-01

    Danish artificial insemination (AI) centres house several boars antibody positive to porcine reproductive and respiratory syndrome virus as well as PRRSV-naive boars which may become acutely infected, The risk of transmission of PRRSV by semen may therefore constitute a serious problem...

  7. Efficacy of CMX001 as a Prophylactic and Presymptomatic Antiviral Agent in New Zealand White Rabbits Infected with Rabbitpox Virus, a Model for Orthopoxvirus Infections of Humans

    Directory of Open Access Journals (Sweden)

    Richard W. Moyer

    2011-01-01

    Full Text Available CMX001, a lipophilic nucleotide analog formed by covalently linking 3‑(hexdecyloxypropan-1-ol to cidofovir (CDV, is being developed as a treatment for smallpox. CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date. Although smallpox has been eliminated from the environment, treatments are urgently being sought due to the risk of smallpox being used as a bioterrorism agent and for monkeypox virus, a zoonotic disease of Africa, and adverse reactions to smallpox virus vaccinations. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Here we first review and discuss the rabbitpox virus (RPV infection of New Zealand White rabbits as a model for smallpox to test the efficacy of CMX001 as a prophylactic and early disease antiviral. Our results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to smallpox vaccination.

  8. Influenza Virus Specific CD8+ T Cells Exacerbate Infection Following High Dose Influenza Challenge of Aged Mice

    Directory of Open Access Journals (Sweden)

    E. M. Parzych

    2013-01-01

    Full Text Available Influenza viruses cause severe illnesses and death, mainly in the aged population. Protection afforded by licensed vaccines through subtype-specific neutralizing antibodies is incomplete, especially when the vaccine antigens fail to closely match those of the circulating viral strains. Efforts are underway to generate a so-called universal influenza vaccine expressing conserved viral sequences that induce broad protection to multiple strains of influenza virus through the induction of CD8+ T cells. Here we assess the effect of a potent antiviral CD8+ T cell response on influenza virus infection of young and aged mice. Our results show that CD8+ T cell-inducing vaccines can provide some protection to young mice, but they exacerbate influenza virus-associated disease in aged mice, causing extensive lung pathology and death.

  9. A Vaccine against CCR5 Protects a Subset of Macaques upon Intravaginal Challenge with Simian Immunodeficiency Virus SIVmac251

    OpenAIRE

    2014-01-01

    As an alternative to targeting human immunodeficiency virus (HIV), we have developed vaccines targeting CCR5, a self-protein critically involved in HIV replication and pathogenesis. By displaying peptides derived from CCR5 at high density on the surface of virus-like particles, we can efficiently induce high-titer IgG antibodies against this self-molecule. Here, we investigated whether prophylactic immunization of rhesus macaques with a particle-based vaccine targeting two regions of macaque ...

  10. Vaccine-induced protection from egg production losses in commercial turkey breeder hens following experimental challenge with a triple-reassortant H3N2 avian influenza virus.

    Science.gov (United States)

    Kapczynski, Darrell R; Gonder, Eric; Liljebjelke, Karen; Lippert, Ron; Petkov, Daniel; Tilley, Becky

    2009-03-01

    Infections of avian influenza virus (AIV) in turkey breeder hens can cause a decrease in both egg production and quality, resulting in significant production losses. In North Carolina in 2003, a triple-reassortant H3N2 AIV containing human, swine, and avian gene segments was isolated from turkey breeder hens (A/turkey/NC/16108/03). This viral subtype was subsequently isolated from both turkeys and swine in Ohio in 2004, and in Minnesota in 2005, and was responsible for significant losses in turkey production. The objective of this study was to determine if currently available commercial, inactivated avian influenza H3 subtype oil-emulsion vaccines would protect laying turkey hens from egg production losses following challenge with the 2003 H3N2 field virus isolate from North Carolina. Laying turkey hens were vaccinated in the field with two injections of either a commercial monovalent (A/duck/Minnesota/79/79 [H3N4]) or autogenous bivalent (A/turkey/North Carolina/05 (H3N2)-A/turkey/North Carolina/88 [H1N1]) vaccine, at 26 and 30 wk of age, and subsequently challenged under BSL 3-Ag conditions at 32 wk of age. Vaccine-induced efficacy was determined as protection from a 50% decrease in egg production and from a decrease in egg quality within 21 days postchallenge. Results indicate that, following a natural route of challenge (eye drop and intranasal), birds vaccinated with the 2005 North Carolina H3N2 subtype were significantly protected from the drop in egg production observed in both the H3N4 vaccinated and sham-vaccinated hens. The results demonstrate that groups receiving vaccines containing either H3 subtype had a decreased number of unsettable eggs, increased hemagglutination inhibition titers following challenge, and decreased virus isolations from cloacal swabs as compared to the sham-vaccinated group. Phylogenetic analysis of the nucleotide sequence of the HA1 gene segment from the three H3 viruses used in these studies indicated that the two North Carolina

  11. Vaccination with recombinant adenoviruses expressing the peste des petits ruminants virus F or H proteins overcomes viral immunosuppression and induces protective immunity against PPRV challenge in sheep.

    Science.gov (United States)

    Rojas, José M; Moreno, Héctor; Valcárcel, Félix; Peña, Lourdes; Sevilla, Noemí; Martín, Verónica

    2014-01-01

    Peste des petits ruminants (PPR) is a highly contagious disease of small ruminants caused by the Morbillivirus peste des petits ruminants virus (PPRV). Two recombinant replication-defective human adenoviruses serotype 5 (Ad5) expressing either the highly immunogenic fusion protein (F) or hemagglutinin protein (H) from PPRV were used to vaccinate sheep by intramuscular inoculation. Both recombinant adenovirus vaccines elicited PPRV-specific B- and T-cell responses. Thus, neutralizing antibodies were detected in sera from immunized sheep. In addition, we detected a significant antigen specific T-cell response in vaccinated sheep against two different PPRV strains, indicating that the vaccine induced heterologous T cell responses. Importantly, no clinical signs and undetectable virus shedding were observed after virulent PPRV challenge in vaccinated sheep. These vaccines also overcame the T cell immunosuppression induced by PPRV in control animals. The results indicate that these adenovirus constructs could be a promising alternative to current vaccine strategies for the development of PPRV DIVA vaccines.

  12. Experimental challenge and pathology of highly pathogenic avian influenza virus H5N1 in dunlin (Calidris alpina), an intercontinental migrant shorebird species

    Science.gov (United States)

    Hall, Jeffrey S.; Franson, J. Christian; Gill, Robert E.; Meteyer, Carol U.; TeSlaa, Joshua L.; Nashold, Sean; Dusek, Robert J.; Ip, Hon S.

    2011-01-01

    Background Shorebirds (Charadriiformes) are considered one of the primary reservoirs of avian influenza. Because these species are highly migratory, there is concern that infected shorebirds may be a mechanism by which highly pathogenic avian influenza virus (HPAIV) H5N1 could be introduced into North America from Asia. Large numbers of dunlin (Calidris alpina) migrate from wintering areas in central and eastern Asia, where HPAIV H5N1 is endemic, across the Bering Sea to breeding areas in Alaska. Low pathogenic avian influenza virus has been previously detected in dunlin, and thus, dunlin represent a potential risk to transport HPAIV to North America. To date no experimental challenge studies have been performed in shorebirds.

  13. H5N1 VLP vaccine induced protection in ferrets against lethal challenge with highly pathogenic H5N1 influenza viruses.

    Science.gov (United States)

    Mahmood, Kutubuddin; Bright, Rick A; Mytle, Nutan; Carter, Donald M; Crevar, Corey J; Achenbach, Jenna E; Heaton, Penny M; Tumpey, Terrence M; Ross, Ted M

    2008-10-03

    In this study, recombinant virus-like particles (VLPs) were evaluated as a candidate vaccine against emerging influenza viruses with pandemic potential. The VLPs are composed of the hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1) proteins of the H5N1 A/Indonesia/05/2005 (clade 2.1; [Indo/05]) virus, which were expressed using baculovirus in Spodoptera frugiperda (Sf9) cells. Ferrets received either 2 injections of the VLP vaccine at escalating doses (based on HA content), recombinant HA, or were mock vaccinated. Vaccinated ferrets were then challenged with either H5N1 Indo/05 or H5N1 A/Viet Nam 1203/2004 (VN/04) wild-type viruses. All ferrets that received the VLP vaccine survived regardless of the VLP dose or challenge strain, whereas seven of eight mock vaccinated ferrets died. The VLP vaccine induced HAI antibodies against the homologous H5N1 clade 2.1 strain, as well as heterologous strains from H5N1 clades 1, 2.2, and 2.3. The magnitude of the HAI titers correlated with VLP dose. Neutralizing antibody responses against the Indo/05 and VN/04 strains showed a similar pattern. Affinity of the anti-HA antibodies raised by the H5N1 Indo/05 VLPs had a higher association rate to the homologous clade 2.1 HA than to the clade 1 (VN/04) HA; however, once bound, antibodies had similar slow disassociation rates. These results provide support for continued development of the H5N1 VLPs as a candidate vaccine against pandemic influenza. Exploration of immunologic correlates of protection for H5N1 vaccines beyond HAI and neutralizing antibody responses is warranted.

  14. BoHV-4-Based Vector Single Heterologous Antigen Delivery Protects STAT1(-/- Mice from Monkeypoxvirus Lethal Challenge.

    Directory of Open Access Journals (Sweden)

    Valentina Franceschi

    2015-06-01

    Full Text Available Monkeypox virus (MPXV is the etiological agent of human (MPX. It is an emerging orthopoxvirus zoonosis in the tropical rain forest of Africa and is endemic in the Congo-basin and sporadic in West Africa; it remains a tropical neglected disease of persons in impoverished rural areas. Interaction of the human population with wildlife increases human infection with MPX virus (MPXV, and infection from human to human is possible. Smallpox vaccination provides good cross-protection against MPX; however, the vaccination campaign ended in Africa in 1980, meaning that a large proportion of the population is currently unprotected against MPXV infection. Disease control hinges on deterring zoonotic exposure to the virus and, barring that, interrupting person-to-person spread. However, there are no FDA-approved therapies against MPX, and current vaccines are limited due to safety concerns. For this reason, new studies on pathogenesis, prophylaxis and therapeutics are still of great interest, not only for the scientific community but also for the governments concerned that MPXV could be used as a bioterror agent. In the present study, a new vaccination strategy approach based on three recombinant bovine herpesvirus 4 (BoHV-4 vectors, each expressing different MPXV glycoproteins, A29L, M1R and B6R were investigated in terms of protection from a lethal MPXV challenge in STAT1 knockout mice. BoHV-4-A-CMV-A29LgD106ΔTK, BoHV-4-A-EF1α-M1RgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK were successfully constructed by recombineering, and their capacity to express their transgene was demonstrated. A small challenge study was performed, and all three recombinant BoHV-4 appeared safe (no weight-loss or obvious adverse events following intraperitoneal administration. Further, BoHV-4-A-EF1α-M1RgD106ΔTK alone or in combination with BoHV-4-A-CMV-A29LgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK, was shown to be able to protect, 100% alone and 80% in combination, STAT1(-/- mice

  15. 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

    Directory of Open Access Journals (Sweden)

    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.

  16. Selection of a rare neutralization-resistant variant following passive transfer of convalescent immune plasma in equine infectious anemia virus-challenged SCID horses.

    Science.gov (United States)

    Taylor, Sandra D; Leib, Steven R; Carpenter, Susan; Mealey, Robert H

    2010-07-01

    Vaccines preventing HIV-1 infection will likely elicit antibodies that neutralize diverse strains. However, the capacity for lentiviruses to escape broadly neutralizing antibodies (NAbs) is not completely understood, nor is it known whether NAbs alone can control heterologous infection. Here, we determined that convalescent immune plasma from a horse persistently infected with equine infectious anemia virus (EIAV) neutralized homologous virus and several envelope variants containing heterologous principal neutralizing domains (PND). Plasma was infused into young horses (foals) affected with severe combined immunodeficiency (SCID), followed by challenge with a homologous EIAV stock. Treated SCID foals were protected against clinical disease, with complete prevention of infection occurring in one foal. In three SCID foals, a novel neutralization-resistant variant arose that was found to preexist at a low frequency in the challenge inoculum. In contrast, SCID foals infused with nonimmune plasma developed acute disease associated with high levels of the predominant challenge virus. Following transfer to an immunocompetent horse, the neutralization-resistant variant induced a single febrile episode and was subsequently controlled in the absence of type-specific NAb. Long-term control was associated with the presence of cytotoxic T lymphocytes (CTL). Our results demonstrate that immune plasma with neutralizing activity against heterologous PND variants can prevent lentivirus infection and clinical disease in the complete absence of T cells. Importantly, however, rare neutralization-resistant envelope variants can replicate in vivo under relatively broad selection pressure, highlighting the need for protective lentivirus vaccines to elicit NAb responses with increased breadth and potency and/or CTL that target conserved epitopes.

  17. Vaccination of sows against type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) before artificial insemination protects against type 2 PRRSV challenge but does not protect against type 1 PRRSV challenge in late gestation

    Science.gov (United States)

    2014-01-01

    The objective of the present study was to determine the effects of the commercially available type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)-based modified live vaccine against type 1 and type 2 PRRSV challenge in pregnant sows. Half of the sows in the study were vaccinated with a type 2 PRRSV-based vaccine 4 weeks prior to artificial insemination while the other half remained non-vaccinated. Sows were then challenged intranasally with type 1 or type 2 PRRSV at 93 days of gestation. The sows which received the type 2 PRRSV-based vaccine followed by type 2 PRRSV challenge had significantly higher neutralizing antibody titers against type 2 PRRSV than they did against type 1 PRRSV. These same sows had higher frequencies of IFN-γ-secreting cells when stimulated with type 2 PRRSV compared to those stimulated with type 1 PRRSV. Subsequent virological evaluation demonstrated that the type 2 PRRSV-based vaccine reduced the type 2 PRRSV load but not the type 1 PRRSV load present in the blood of the sows. Additionally, vaccination of pregnant sows with the type 2 PRRSV-based vaccine effectively reduced the level of type 2 PRRSV nucleic acids observed in fetal tissues from type 2 PRRSV-challenged sows but did not reduce the level of type 1 PRRSV nucleic acid observed in fetal tissues from type 1 PRRSV-challenged sows. This study demonstrates that the vaccination of pregnant sows with the type 2 PRRSV-based vaccine protects against type 2 PRRSV challenge but does not protect against type 1 PRRSV challenge. PMID:24484238

  18. An immersion of Gracilaria tenuistipitata extract improves the immunity and survival of white shrimp Litopenaeus vannamei challenged with white spot syndrome virus.

    Science.gov (United States)

    Lin, Yong-Chin; Yeh, Su-Tuen; Li, Chang-Che; Chen, Li-Li; Cheng, Ann-Chang; Chen, Jiann-Chu

    2011-12-01

    The innate immunity and resistance against white spot syndrome virus (WSSV) in white shrimp Litopenaeus vannamei which received the Gracilaria tenuistipitata extract were examined. Shrimp immersed in seawater containing the extract at 0 (control), 400 and 600 mg L(-1) for 3 h were challenged with WSSV at 2 × 10(4) copies shrimp(-1). Shrimp not exposed to the extract and not received WSSV challenge served as unchallenged control. The survival rate of shrimp immersed in 400 mg L(-1) or 600 mg L(-1) extract was significantly higher than that of challenged control shrimp over 24-120 h. The haemocyte count, phenoloxidase activity, respiratory burst, superoxide dismutase activity, and lysozyme activity of shrimp immersed in 600 mg L(-1) extract were significantly higher than those of unchallenged control shrimp at 6, 6, 6, 6, and 6-24 h post-challenge. In another experiment, shrimp which had received 3 h immersion of 0, 400, 600 mg L(-1) extract were challenged with WSSV. The shrimp were then received a booster (3 h immersion in the same dose of the extract), and the immune parameters were examined at 12-120 h post-challenge. The immune parameters of shrimp immersed in 600 mg L(-1) extract, and then received a booster at 9, 21, and 45 h were significantly higher than those of unchallenged control shrimp at 12-48 h post-challenge. In conclusion, shrimp which had received the extract exhibited protection against WSSV as evidenced by the higher survival rate and higher values of immune parameters. Shrimp which had received the extract and infected by WSSV showed improved immunity when they received a booster at 9, 21, and 45 h post-WSSV challenge. The extract treatment caused less decrease in PO activity, and showed better performance of lysozyme activity and antioxidant response in WSSV-infected shrimp.

  19. Challenges of Generating and Maintaining Protective Vaccine-Induced Immune Responses for Foot-and-Mouth Disease Virus in Pigs

    Science.gov (United States)

    Lyons, Nicholas A.; Lyoo, Young S.; King, Donald P.; Paton, David J.

    2016-01-01

    Vaccination can play a central role in the control of outbreaks of foot-and-mouth disease (FMD) by reducing both the impact of clinical disease and the extent of virus transmission between susceptible animals. Recent incursions of exotic FMD virus lineages into several East Asian countries have highlighted the difficulties of generating and maintaining an adequate immune response in vaccinated pigs. Factors that impact vaccine performance include (i) the potency, antigenic payload, and formulation of a vaccine; (ii) the antigenic match between the vaccine and the heterologous circulating field strain; and (iii) the regime (timing, frequency, and herd-level coverage) used to administer the vaccine. This review collates data from studies that have evaluated the performance of foot-and-mouth disease virus vaccines at the individual and population level in pigs and identifies research priorities that could provide new insights to improve vaccination in the future. PMID:27965966

  20. Comparison of vaccine efficacy for different antigen delivery systems for infectious pancreatic necrosis virus vaccines in Atlantic salmon (Salmo salar L.) in a cohabitation challenge model.

    Science.gov (United States)

    Munang'andu, Hetron M; Fredriksen, Børge N; Mutoloki, Stephen; Brudeseth, Bjørn; Kuo, Tsun-Yung; Marjara, Inderjit S; Dalmo, Roy A; Evensen, Øystein

    2012-06-01

    Two strains of IPNV made by reverse genetics on the Norwegian Sp strain NVI-015 (GenBank AY379740) backbone encoding the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs were used to prepare inactivated whole virus (IWV), nanoparticle vaccines with whole virus, Escherichia coli subunit encoding truncated VP2-TA and VP2-PT, VP2-TA and VP2-PT fusion antigens with putative translocating domains of Pseudomonas aeruginosa exotoxin, and plasmid DNA encoding segment A of the TA strain. Post challenge survival percentages (PCSP) showed that IWV vaccines conferred highest protection (PCSP=42-53) while nanoparticle, sub-unit recombinant and DNA vaccines fell short of the IWV vaccines in Atlantic salmon (Salmo salar L.) postsmolts challenged with the highly virulent Sp strain NVI-015 (TA strain) of IPNV after 560 degree days post vaccination. Antibody levels induced by these vaccines did not show antigenic differences between the virulent and avirulent motifs for vaccines made with the same antigen dose and delivery system after 8 weeks post vaccination. Our findings show that fish vaccinated with less potent vaccines comprising of nanoparticle, DNA and recombinant vaccines got infected much earlier and yielded to higher infection rates than fish vaccinated with IWV vaccines that were highly potent. Ability of the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs to limit establishment of infection showed equal protection for vaccines made of the same antigen dose and delivery systems. Prevention of tissue damage linked to viral infection was eminent in the more potent vaccines than the less protective ones. Hence, there still remains the challenge of developing highly efficacious vaccines with the ability to eliminate the post challenge carrier state in IPNV vaccinology.

  1. Molecular and biological comparison of two Tomato Yellow Ring Virus (TYRV) isolates: challenging the Tospovirus species concept

    NARCIS (Netherlands)

    Hassani-Mehraban, A.; Saaijer, J.; Peters, D.; Goldbach, R.W.; Kormelink, R.J.M.

    2007-01-01

    Two strains of Tomato yellow ring virus (TYRV, genus Tospovirus), one from tomato (referred to as TYRV-t) and the other from soybean and potato (denoted TYRV-s), collected from different geographical regions in Iran, were compared. Their genomic S RNA segments differed in size by 55 nucleotides. Com

  2. Vaccination with experimental feline immunodeficiency virus vaccines, based on autologous infected cells, elicits enhancement of homologous challenge infection

    NARCIS (Netherlands)

    J.A. Karlas (Jos); C.H.J. Siebelink (Kees); M.A. Peer; W. Huisman (Willem); A.M. Cuisinier; G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Ab)

    1999-01-01

    textabstractCats were vaccinated with fixed autologous feline immunodeficiency virus (FIV)-infected cells in order to present viral proteins to the immune system of individual cats in an MHC-matched fashion. Upon vaccination, a humoral response against Gag was induced. Furthermore,

  3. 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.

  4. Informing the Historical Record of Experimental Nonhuman Primate Infections with Ebola Virus: Genomic Characterization of USAMRIID Ebola Virus/H.sapiens-tc/COD/1995/Kikwit-9510621 Challenge Stock "R4368" and Its Replacement "R4415".

    Science.gov (United States)

    Kugelman, Jeffrey R; Rossi, Cynthia A; Wiley, Michael R; Ladner, Jason T; Nagle, Elyse R; Pfeffer, Bradley P; Garcia, Karla; Prieto, Karla; Wada, Jiro; Kuhn, Jens H; Palacios, Gustavo

    2016-01-01

    The creation of licensed medical countermeasures against Select Agents such as Ebola virus (EBOV) is critically dependent on the use of standardized reagents, assays, and animal models. We performed full genome reconstruction, population genomics, contaminant analysis, and characterization of the glycoprotein gene editing site of historical United States Army Medical Research Institute of Infectious Diseases (USAMRIID) nonhuman-primate challenge stock Ebola virus Kikwit "R4368" and its 2014 replacement "R4415." We also provide characterization of the master stock used to create "R4415." The obtained data are essential to understanding the quality of the seed stock reagents used in pivotal animal studies that have been used to inform medical countermeasure development. Furthermore, these data might add to the understanding of the influence of EBOV variant populations on pathogenesis and disease outcome and inform attempts to avoid the evolution of EBOV escape mutants in response to current therapeutics. Finally, as the primary challenge stocks have changed over time, these data will provide a baseline for understanding and correlating past and future animal study results.

  5. Informing the Historical Record of Experimental Nonhuman Primate Infections with Ebola Virus: Genomic Characterization of USAMRIID Ebola Virus/H.sapiens-tc/COD/1995/Kikwit-9510621 Challenge Stock "R4368" and Its Replacement "R4415".

    Directory of Open Access Journals (Sweden)

    Jeffrey R Kugelman

    Full Text Available The creation of licensed medical countermeasures against Select Agents such as Ebola virus (EBOV is critically dependent on the use of standardized reagents, assays, and animal models. We performed full genome reconstruction, population genomics, contaminant analysis, and characterization of the glycoprotein gene editing site of historical United States Army Medical Research Institute of Infectious Diseases (USAMRIID nonhuman-primate challenge stock Ebola virus Kikwit "R4368" and its 2014 replacement "R4415." We also provide characterization of the master stock used to create "R4415." The obtained data are essential to understanding the quality of the seed stock reagents used in pivotal animal studies that have been used to inform medical countermeasure development. Furthermore, these data might add to the understanding of the influence of EBOV variant populations on pathogenesis and disease outcome and inform attempts to avoid the evolution of EBOV escape mutants in response to current therapeutics. Finally, as the primary challenge stocks have changed over time, these data will provide a baseline for understanding and correlating past and future animal study results.

  6. An attenuated herpes simplex virus type 1 (HSV1 encoding the HIV-1 Tat protein protects mice from a deadly mucosal HSV1 challenge.

    Directory of Open Access Journals (Sweden)

    Mariaconcetta Sicurella

    Full Text Available Herpes simplex virus types 1 and 2 (HSV1 and HSV2 are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat. In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ, induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1

  7. The bovine viral diarrhea virus E2 protein formulated with a novel adjuvant induces strong, balanced immune responses and provides protection from viral challenge in cattle.

    Science.gov (United States)

    Snider, Marlene; Garg, Ravendra; Brownlie, Robert; van den Hurk, Jan V; van Drunen Littel-van den Hurk, Sylvia

    2014-11-28

    Bovine viral diarrhea virus (BVDV) is still one of the most serious pathogens in cattle, meriting the development of improved vaccines. Recently, we developed a new adjuvant consisting of poly[di(sodium carboxylatoethylphenoxy)]-phosphazene (PCEP), either CpG ODN or poly(I:C), and an immune defense regulator (IDR) peptide. As this adjuvant has been shown to mediate the induction of robust, balanced immune responses, it was evaluated in an E2 subunit vaccine against BVDV in lambs and calves. The BVDV type 2 E2 protein was produced at high levels in a mammalian expression system and purified. When formulated with either CpG ODN or poly(I:C), together with IDR and PCEP, the E2 protein elicited high antibody titers and production of IFN-γ secreting cells in lambs. As the immune responses were stronger when poly(I:C) was used, the E2 protein with poly(I:C), IDR and PCEP was subsequently tested in cattle. Robust virus neutralizing antibodies as well as cell-mediated immune responses, including CD8(+) cytotoxic T cell (CTL) responses, were induced. The fact that CTL responses were demonstrated in calves vaccinated with an E2 protein subunit vaccine indicates that this adjuvant formulation promotes cross-presentation. Furthermore, upon challenge with a high dose of virulent BVDV-2, the vaccinated calves showed almost no temperature response, weight loss, leukopenia or virus replication, in contrast to the control animals, which had severe clinical disease. These data suggest that this E2 subunit formulation induces significant protection from BVDV-2 challenge, and thus is a promising BVDV vaccine candidate; in addition, the adjuvant platform has applications in bovine vaccines in general.

  8. A review of the vector management methods to prevent and control outbreaks of West Nile virus infection and the challenge for Europe

    Science.gov (United States)

    2014-01-01

    West Nile virus infection is a growing concern in Europe. Vector management is often the primary option to prevent and control outbreaks of the disease. Its implementation is, however, complex and needs to be supported by integrated multidisciplinary surveillance systems and to be organized within the framework of predefined response plans. The impact of the vector control measures depends on multiple factors and the identification of the best combination of vector control methods is therefore not always straightforward. Therefore, this contribution aims at critically reviewing the existing vector control methods to prevent and control outbreaks of West Nile virus infection and to present the challenges for Europe. Most West Nile virus vector control experiences have been recently developed in the US, where ecological conditions are different from the EU and vector control is organized under a different regulatory frame. The extrapolation of information produced in North America to Europe might be limited because of the seemingly different epidemiology in the European region. Therefore, there is an urgent need to analyse the European experiences of the prevention and control of outbreaks of West Nile virus infection and to perform robust cost-benefit analysis that can guide the implementation of the appropriate control measures. Furthermore, to be effective, vector control programs require a strong organisational backbone relying on a previously defined plan, skilled technicians and operators, appropriate equipment, and sufficient financial resources. A decision making guide scheme is proposed which may assist in the process of implementation of vector control measures tailored on specific areas and considering the available information and possible scenarios. PMID:25015004

  9. Effect of timing of challenge following short-term natural exposure to bovine viral diarrhea virus type 1b on animal performance and immune response in beef steers.

    Science.gov (United States)

    Carlos-Valdez, L; Wilson, B K; Burciaga-Robles, L O; Step, D L; Holland, B P; Richards, C J; Montelongo, M A; Confer, A W; Fulton, R W; Krehbiel, C R

    2016-11-01

    Bovine respiratory disease (BRD) is the most common and economically detrimental disease of beef cattle during the postweaning period, causing the majority of morbidity and mortality in feedlots. The pathogenesis of this disease often includes an initial viral infection, which can predispose cattle to a secondary bacterial infection. The objective of this experiment was to determine the effects of timing of an intratracheal (MH) challenge relative to 72 h of natural exposure to bovine viral diarrhea virus (BVDV) type 1b persistently infected (PI) calves on performance, serum antibody production, total and differential white blood cell (WBC) count, rectal temperature, clinical severity score (CS), and haptoglobin (Hp). Steers ( = 24; 276 ± 31 kg initial BW) were randomly allocated to 1 of 3 treatments (8 steers/treatment) in a randomized complete block design. Treatments were steers not exposed to calves PI with BVDV 1b and not challenged with MH (CON), steers intratracheally challenged with MH 84 h after being exposed to calves PI with BVDV 1b for 72 h (LateCh), and steers intratracheally challenged with MH 12 h after being exposed to calves PI with BVDV 1b for 72 h (EarlyCh). Performance (ADG, DMI, and G:F) was decreased ( marketing channels allow for variation in the timing of respiratory pathogen exposure, understanding the physiological changes in morbid cattle will lead to improved management of BRD.

  10. The challenge of detecting classical swine fever virus circulation in wild boar (Sus scrofa): Simulation of sampling options

    DEFF Research Database (Denmark)

    Schulz, Jana; Schulz, Katja; Blome, Sandra;

    2016-01-01

    populations can be a major cause of primary outbreaks in domestic pigs, strict control measures for both species were implemented. To guarantee early detection and to demonstrate freedom from disease, intensive surveillance is carried out based on a hunting bag sample. In this context, virologic...... investigations play a major role in the early detection of new introductions and in regions immunized with a conventional vaccine. The required financial resources and personnel for reliable testing are often large, and sufficient sample sizes to detect low virus prevalences are difficult to obtain. We conducted...... a simulation to model the possible impact of changes in sample size and sampling intervals on the probability of CSF virus detection based on a study area of 65 German hunting grounds. A 5-yr period with 4,652 virologic investigations was considered. Results suggest that low prevalences could not be detected...

  11. Challenges and Strategies of Laboratory Diagnosis for Newly Emerging Influenza Viruses in Taiwan: A Decade after SARS

    Directory of Open Access Journals (Sweden)

    Jih-Hui Lin

    2015-01-01

    Full Text Available Since the first case of severe acute respiratory syndrome (SARS in Taiwan was identified in March 2003, viral respiratory infections, in particular the influenza virus, have become a national public health concern. Taiwan would face a serious threat of public health problems if another SARS epidemic overlapped with a flu outbreak. After SARS, the Taiwan Centers for Disease Control accelerated and strengthened domestic research on influenza and expanded the exchange of information with international counterparts. The capacity of influenza A to cross species barriers presents a potential threat to human health. Given the mutations of avian flu viruses such as H7N9, H6N1, and H10N8, all countries, including Taiwan, must equip themselves to face a possible epidemic or pandemic. Such preparedness requires global collaboration.

  12. Direct-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challenge.

    Science.gov (United States)

    De Monte, Anne; Courjon, Johan; Anty, Rodolphe; Cua, Eric; Naqvi, Alissa; Mondain, Véronique; Cottalorda, Jacqueline; Ollier, Laurence; Giordanengo, Valérie

    2016-05-01

    Use of direct-acting antiviral drugs (DAAs) greatly improves management of adults infected with hepatitis C virus (HCV) whether patients are treatment-naive or unsuccessfully pre-treated. Several inhibitors of viral nonstructural proteins (NS3/4A protease, NS5A and NS5B polymerase) allow a rapid HCV clearance and increase rates of sustained virological response. Both the EASL and AASLD guidelines have recently published up-to-date recommendations for their use, addressing each HCV genotype and particular situations. However, management of patients coinfected with hepatitis B virus (HBV) has been developed by these guidelines with reference to cases of HBV reactivation reported during previous anti-HCV regimens containing interferon known active against both HBV and HCV. In the setting of the interferon-free HCV therapies with DAAs only, the possibility of HBV reactivation during treatment of hepatitis C is raised due to viral interferences in HCV/HBV coinfected persons. Herein, we report a case of early HBV reactivation during DAAs-based anti-HCV treatment (ledipasvir/sofosbuvir) in a patient having a resolved HBV infection and chronically infected with HCV genotype 4 and HIV. Moreover, we review similar recent cases of HBV reactivation in patients infected with HBV and HCV genotype 1 during treatment of hepatitis C by regimen incorporating other combination of DAAs (sofosbuvir/simeprevir or daclatasvir/asunaprevir). Due to the potential risk of early HBV reactivation in HCV/HBV-coinfected patients during interferon-free DAAs-based HCV therapies, altogether these cases highlight the necessity to closely monitor HBV coinfection, regardless its stage (chronic, occult, resolved), whatever HCV genotype or class of DAAs used.

  13. THE CHALLENGE OF DETECTING CLASSICAL SWINE FEVER VIRUS CIRCULATION IN WILD BOAR (SUS SCROFA): SIMULATION OF SAMPLING OPTIONS.

    Science.gov (United States)

    Sonnenburg, Jana; Schulz, Katja; Blome, Sandra; Staubach, Christoph

    2016-10-01

    Classical swine fever (CSF) is one of the most important viral diseases of domestic pigs ( Sus scrofa domesticus) and wild boar ( Sus scrofa ). For at least 4 decades, several European Union member states were confronted with outbreaks among wild boar and, as it had been shown that infected wild boar populations can be a major cause of primary outbreaks in domestic pigs, strict control measures for both species were implemented. To guarantee early detection and to demonstrate freedom from disease, intensive surveillance is carried out based on a hunting bag sample. In this context, virologic investigations play a major role in the early detection of new introductions and in regions immunized with a conventional vaccine. The required financial resources and personnel for reliable testing are often large, and sufficient sample sizes to detect low virus prevalences are difficult to obtain. We conducted a simulation to model the possible impact of changes in sample size and sampling intervals on the probability of CSF virus detection based on a study area of 65 German hunting grounds. A 5-yr period with 4,652 virologic investigations was considered. Results suggest that low prevalences could not be detected with a justifiable effort. The simulation of increased sample sizes per sampling interval showed only a slightly better performance but would be unrealistic in practice, especially outside the main hunting season. Further studies on other approaches such as targeted or risk-based sampling for virus detection in connection with (marker) antibody surveillance are needed.

  14. Non-typeable Haemophilus influenzae protects human airway epithelial cells from a subsequent respiratory syncytial virus challenge.

    Science.gov (United States)

    Hartwig, Stacey M; Ketterer, Margaret; Apicella, Michael A; Varga, Steven M

    2016-11-01

    Respiratory syncytial virus (RSV) and the common commensal and opportunistic pathogen, non-typeable Haemophilus influenzae (NTHi) both serve as a frequent cause of respiratory infection in children. Although it is well established that some respiratory viruses can increase host susceptibility to secondary bacterial infections, few studies have examined how commensal bacteria could influence a secondary viral response. Here, we examined the impact of NTHi exposure on a subsequent RSV infection of human bronchial epithelial cells (16HBE14o-). Co-culture of 16HBE14o- cells with NTHi resulted in inhibition of viral gene expression following RSV infection. 16HBE14o- cells co-cultured with heat-killed NTHi failed to protect against an RSV infection, indicating that protection requires live bacteria. However, NTHi did not inhibit influenza A virus replication, indicating that NTHi-mediated protection was RSV-specific. Our data demonstrates that prior exposure to a commensal bacterium such as NTHi can elicit protection against a subsequent RSV infection.

  15. Depo-provera treatment does not abrogate protection from intravenous SIV challenge in female macaques immunized with an attenuated AIDS virus.

    Directory of Open Access Journals (Sweden)

    Meritxell Genescà

    Full Text Available BACKGROUND: In a previous study, progesterone treatment of female monkeys immunized with live, attenuated SHIV89.6 abrogated the generally consistent protection from vaginal simian immunodeficiency virus (SIV challenge. The mechanisms responsible for the loss of protection remain to be defined. The objective of the present study was to determine whether Depo-Provera administration alters protection from intravenous SIV challenge in SHIV-immunized female macaques. METHODS AND FINDINGS: Two groups of female macaques were immunized with attenuated SHIV89.6 and then challenged intravenously with SIVmac239. Four weeks before challenge, one animal group was treated with Depo-Provera, a commonly used injectable contraceptive progestin. As expected, SHIV-immunized monkeys had significantly lower peak and set-point plasma viral RNA levels compared to naïve controls, but in contrast to previously published findings with vaginal SIV challenge, the Depo-Provera SHIV-immunized animals controlled SIV replication to a similar, or even slightly greater, degree than did the untreated SHIV-immunized animals. Control of viral replication from week 4 to week 20 after challenge was more consistent in the progesterone-treated, SHIV-immunized animals than in untreated, SHIV-immunized animals. Although levels of interferon-gamma production were similar, the SIV-specific CD8(+ T cells of progesterone-treated animals expressed more functions than the anti-viral CD8(+ T cells from untreated animals. CONCLUSIONS: Depo-Provera did not diminish the control of viral replication after intravenous SIV challenge in female macaques immunized with a live-attenuated lentivirus. This result contrasts with the previously reported effect of Depo-Provera(R on protection from vaginal SIV challenge and strongly implies that the decreased protection from vaginal challenge is due to effects of progesterone on the genital tract rather than to systemic effects. Further, these results

  16. Optimisations and challenges involved in the creation of various bioluminescent and fluorescent influenza a virus strains for in vitro and in vivo applications

    NARCIS (Netherlands)

    M.I. Spronken (Monique); K.R. Short (Kirsty); S. Herfst (Sander); T.M. Bestebroer (Theo); Vaes, V.P. (Vincent P.); Van Der Hoeven, B. (Barbara); A.J. Koster (Abraham J.); G.J. Kremers (Gert-Jan); D.P. Scott (Dana P.); A.P. Gultyaev (Alexander); Sorell, E.M. (Erin M.); M.T. de Graaf (Marieke); M. Bárcena (Montserrat); G.F. Rimmelzwaan (Guus); R.A.M. Fouchier (Ron)

    2015-01-01

    textabstractBioluminescent and fluorescent influenza A viruses offer new opportunities to study influenza virus replication, tropism and pathogenesis. To date, several influenza A reporter viruses have been described. These strategies typically focused on a single reporter gene (either

  17. Chasing Jenner's vaccine: revisiting cowpox virus classification.

    Directory of Open Access Journals (Sweden)

    Darin S Carroll

    Full Text Available Cowpox virus (CPXV is described as the source of the first vaccine used to prevent the onset and spread of an infectious disease. It is one of the earliest described members of the genus Orthopoxvirus, which includes the viruses that cause smallpox and monkeypox in humans. Both the historic and current literature describe "cowpox" as a disease with a single etiologic agent. Genotypic data presented herein indicate that CPXV is not a single species, but a composite of several (up to 5 species that can infect cows, humans, and other animals. The practice of naming agents after the host in which the resultant disease manifests obfuscates the true taxonomic relationships of "cowpox" isolates. These data support the elevation of as many as four new species within the traditional "cowpox" group and suggest that both wild and modern vaccine strains of Vaccinia virus are most closely related to CPXV of continental Europe rather than the United Kingdom, the homeland of the vaccine.

  18. Patterns of Cellular Immunity Associated with Experimental Infection with rDEN2Δ30 (Tonga/74) Support Its Suitability as a Human Dengue Virus Challenge Strain.

    Science.gov (United States)

    Grifoni, Alba; Angelo, Michael; Sidney, John; Paul, Sinu; Peters, Bjoern; de Silva, Aruna D; Phillips, Elizabeth; Mallal, Simon; Diehl, Sean A; Botten, Jason; Boyson, Jonathan; Kirkpatrick, Beth D; Whitehead, Stephen S; Durbin, Anna P; Sette, Alessandro; Weiskopf, Daniela

    2017-04-15

    A deletion variant of the dengue virus (DENV) serotype 2 (DENV2) Tonga/74 strain lacking 30 nucleotides from its 3' untranslated region (rDEN2Δ30) has previously been established for use in a controlled human DENV challenge model. To evaluate if this model is appropriate for the derivation of correlates of protection for DENV vaccines on the basis of cellular immunity, we wanted to compare the cellular immune response to this challenge strain to the response induced by natural infection. To achieve this, we predicted HLA class I- and class II-restricted peptides from rDEN2Δ30 and used them in a gamma interferon enzyme-linked immunosorbent spot assay to interrogate CD8(+) and CD4(+) T cell responses in healthy volunteers infected with rDEN2Δ30. At the level of CD8 responses, vigorous ex vivo responses were detected in approximately 80% of donors. These responses were similar in terms of the magnitude and the numbers of epitopes recognized to the responses previously observed in peripheral blood mononuclear cells from donors from regions where DENV is hyperendemic. The similarity extended to the immunodominance hierarchy of the DENV nonstructural proteins, with NS3, NS5, and NS1 being dominant in both donor cohorts. At the CD4 level, the responses to rDEN2Δ30 vaccination were less vigorous than those to natural DENV infection and were more focused on nonstructural proteins. The epitopes recognized following rDEN2Δ30 infection and natural infection were largely overlapping for both the CD8 (100%) and CD4 (85%) responses. Finally, rDEN2Δ30 induced stronger CD8 responses than other, more attenuated DENV isolates.IMPORTANCE The lack of a known correlate of protection and the failure of a neutralizing antibody to correlate with protection against dengue virus have highlighted the need for a human DENV challenge model to better evaluate the candidate live attenuated dengue vaccines. In this study, we sought to characterize the immune profiles of rDEN2Δ30-infected

  19. Smallpox vaccination and bioterrorism with pox viruses.

    Science.gov (United States)

    Mayr, Anton

    2003-10-01

    Bioterrorist attacks occupy a special place amongst the innumerable potential types of terrorist attack, with the intentional release of pox viruses being especially feared in this connection. Apart from the variola virus, the agent responsible for smallpox in humans, the monkeypox virus and numerous other animal pox viruses pose potential risks for humans and animals. This risk scenario also includes recombinations between the various pox viruses, changes in hosts and genetically engineered manipulations of pox viruses. For over 200 years, the method of choice for combatting smallpox was via vaccination with a reproductive, original vaccinia virus. Worldwide eradication of smallpox at the end of the 1970s and the discontinuation of routine smallpox vaccination in 1980 can be credited to such vaccination. Unfortunately, these vaccinations were associated with a large number of postvaccinal impairments, sometimes resulting in death (e.g. postvaccinal encephalitis). The only way to restrict such postvaccinal complications was to carry out initial vaccination within the first 2 postnatal years. Initial vaccination at a later age led to such a sharp increase in the number of vaccines with complications that vaccination had to be discouraged. The dilemma of the smallpox vaccine stocks stems from the fact that a large portion of these stocks are produced with the same vaccinia strains as before. This is irresponsible, especially as the percentage of immune-suppressed persons in the population, for whom vaccination-related complications pose an especial threat, is increasing. One solution to the dilemma of the smallpox vaccine stocks is the MVA strain. It is harmless, protects humans and animals equally well against smallpox and can be applied parenterally.

  20. Effects of germanium biotite supplement on immune responses of vaccinated mini-pigs to foot-and-mouth disease virus challenge.

    Science.gov (United States)

    Jung, Myunghwan; Park, Hong-Tea; Park, Jong-Hyeon; Lee, Kwang-Nyeong; Shin, Seung Won; Shin, Min-Kyoung; Sung, Kyung Yong; Jung, Yeon-Kwon; Kim, Byounghan; Yoo, Han Sang

    2015-01-01

    Since the outbreaks of foot-and-mouth disease (FMD) in South Korea in 2010-2011, a trivalent vaccine has been used as a routine vaccination. Despite the high efficacy of the trivalent vaccine, low antibody formation was reported in the pig industry and there is considerable concern about the ability of the vaccine to protect against the Andong strain responsible for recent outbreaks in South Korea. To overcome these problems, immunostimulators have been widely used to improve vaccine efficacy in South Korea, although without any scientific evidence. Based on the current situation, the aim of this study was to investigate the effects of germanium biotite, a feed supplement used to enhance the immune system, on the immune responses to FMD vaccination through the Andong strain challenge experiment in trivalent vaccinated pigs. Following the challenge, the germanium biotite-fed pigs showed high levels of IL-8 in serum, and increased cellular immune responses to stimulation with the Andong strain antigen compared to nonsupplemented pigs. In addition, higher FMD virus (FMDV) neutralizing antibody titers were detected in the germanium biotite-fed group than in the nonsupplemented group before the challenge. The findings of this study indicate that germanium biotite supplement might enhance immune responses to the FMD vaccine in pigs.

  1. Enhanced mucosal immunoglobulin A response and solid protection against foot-and-mouth disease virus challenge induced by a novel dendrimeric peptide.

    Science.gov (United States)

    Cubillos, Carolina; de la Torre, Beatriz G; Jakab, Annamaria; Clementi, Giorgia; Borrás, Eva; Bárcena, Juan; Andreu, David; Sobrino, Francisco; Blanco, Esther

    2008-07-01

    The successful use of a dendrimeric peptide to protect pigs against challenge with foot-and-mouth disease virus (FMDV), which causes the most devastating animal disease worldwide, is described. Animals were immunized intramuscularly with a peptide containing one copy of a FMDV T-cell epitope and branching out into four copies of a B-cell epitope. The four immunized pigs did not develop significant clinical signs upon FMDV challenge, neither systemic nor mucosal FMDV replication, nor was its transmission to contact control pigs observed. The dendrimeric construction specifically induced high titers of FMDV-neutralizing antibodies and activated FMDV-specific T cells. Interestingly, a potent anti-FMDV immunoglobulin A response (local and systemic) was observed, despite the parenteral administration of the peptide. On the other hand, peptide-immunized animals showed no antibodies specific of FMDV infection, which qualifies the peptide as a potential marker vaccine. Overall, the dendrimeric peptide used elicited an immune response comparable to that found for control FMDV-infected pigs that correlated with a solid protection against FMDV challenge. Dendrimeric designs of this type may hold substantial promise for peptide subunit vaccine development.

  2. Analysis of Virus Algorithms

    Directory of Open Access Journals (Sweden)

    Jyoti Kalyani

    2006-01-01

    Full Text Available Security of wired and wireless networks is the most challengeable in today's computer world. The aim of this study was to give brief introduction about viruses and worms, their creators and characteristics of algorithms used by viruses. Here wired and wireless network viruses are elaborated. Also viruses are compared with human immune system. On the basis of this comparison four guidelines are given to detect viruses so that more secure systems are made. While concluding this study it is found that the security is most challengeable, thus it is required to make more secure models which automatically detect viruses and prevent the system from its affect.

  3. Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro.

    Directory of Open Access Journals (Sweden)

    Ussama M Abdel-Motal

    Full Text Available BACKGROUND: Although cervico-vaginal epithelial cells of the female lower genital tract provide the initial defense system against HIV-1 infection, the protection is sometimes incomplete. Thus, enhancing anti-HIV-1 humoral immunity at the mucosal cell surface by local expression of anti-HIV-1 broadly neutralizing antibodies (BnAb that block HIV-1 entry would provide an important new intervention that could slow the spread of HIV/AIDS. METHODS AND FINDINGS: This study tested the hypothesis that adeno-associated virus (AAV-BnAb gene transfer to cervico-vaginal epithelial cells will lead to protection against HIV-1. Accordingly, a recombinant AAV vector that encodes human b12 anti-HIV gp120 BnAb as a single-chain variable fragment Fc fusion (scFvFc, or "minibody" was constructed. The secreted b12 minibody was shown to be biologically functional in binding to virus envelope protein, neutralizing HIV-1 and importantly, blocking transfer and infectivity of HIV-1(bal in an organotypic human vaginal epithelial cell (VEC model. Furthermore, cervico-vaginal epithelial stem cells were found to be efficiently transduced by the optimal AAV serotype mediated expression of GFP. CONCLUSION: This study provides the foundation for a novel microbicide strategy to protect against sexual transmission of HIV-1 by AAV transfer of broadly neutralizing antibody genes to cervico-vaginal epithelial stem cells that could replenish b12 BnAb secreting cells through multiple menstrual cycles.

  4. Intervention strategies to reduce the risk of zoonotic infection with avian influenza viruses: scientific basis, challenges and knowledge gaps.

    Science.gov (United States)

    Sims, Leslie D

    2013-09-01

    A range of measures has been recommended and used for the control and prevention of avian influenza. These measures are based on the assessment of local epidemiological situations, field observations and other scientific information. Other non-technical factors are (or in some cases should be) taken into account when developing and recommending control measures. The precise effects under field conditions of most individual interventions applied to control and prevent avian influenza have not been established or subjected to critical review, often because a number of measures are applied simultaneously without controls. In most cases, the combination of measures used results in control or elimination of the virus although there are some countries where this has not been the case. In others, especially those with low poultry density, it is not clear whether the link between the adoption of a set of measures and the subsequent control of the disease is causative. This article discusses the various measures recommended, with particular emphasis on stamping out and vaccination, examines how these measures assist in preventing zoonotic infections with avian influenza viruses and explores gaps in knowledge regarding their effectiveness.

  5. Flow cytometric assessment of chicken T cell-mediated immune responses after Newcastle disease virus vaccination and challenge

    DEFF Research Database (Denmark)

    Dalgaard, T. S.; Norup, L. R.; Pedersen, A.R.

    2010-01-01

    . Despite a delayed NDV-specific antibody response to vaccination, L133 appeared to be better protected than L130 in the subsequent infection challenge as determined by the presence of viral genomes. Peripheral blood was analyzed by flow cytometry and responses in vaccinated/challenged birds were studied....... Furthermore, peripheral lymphocytes from L133 exhibited a significantly higher expression of CD44 and CD45 throughout the experiment. Interestingly, also vaccine-induced differences were observed in L133 as immune chickens had a significantly higher CD45 expression on their lymphocytes than the naïve controls....... Immune chickens from both lines had a significantly higher frequency of circulating γδ T cells than the naïve controls both after vaccination and challenge. Finally, the proliferative capacity of peripheral CD4+ and CD8+ cells specific for NDV was addressed 3 weeks after vaccination and 1 week after...

  6. A novel inactivated gE/gI deleted pseudorabies virus (PRV) vaccine completely protects pigs from an emerged variant PRV challenge.

    Science.gov (United States)

    Gu, Zhenqing; Dong, Jing; Wang, Jichun; Hou, Chengcai; Sun, Haifeng; Yang, Wenping; Bai, Juan; Jiang, Ping

    2015-01-02

    A highly virulent and antigenic variant of pseudorabies virus (PRV) broke out in China at the end of 2011 and caused great economic loss in the pig industry. In this study, an infectious bacterial artificial chromosome (BAC) clone containing the full-length genome of the emerged variant PRV ZJ01 strain was generated. The BAC-derived viruses, vZJ01-GFPΔgE/gI (gE/gI deleted strain, and exhibiting green autofluorescence), vZJ01ΔgE/gI (gE/gI deleted strain), and vZJ01gE/gI-R (gE/gI revertant strain), showed similar in vitro growth to their parent strain. In pigs, inactivated vZJ01ΔgE/gI vaccine generated significantly high levels of neutralizing antibodies against ZJ01 compared with Bartha-K61 live vaccine (pgI vaccine group survived without exhibiting any clinical sings, but two of five animals exhibited central nervous signs in the Bartha-K61 group. Meanwhile, all the non-vaccinated control animals died at 7 days post-challenge. This indicates that the inactivated vZJ01ΔgE/gI vaccine is a promising vaccine candidate for controlling the variant strains of PRV now circulating in China. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Novel chimeric foot-and-mouth disease virus-like particles harboring serotype O VP1 protect guinea pigs against challenge.

    Science.gov (United States)

    Li, Haitao; Li, Zhiyong; Xie, Yinli; Qin, Xiaodong; Qi, Xingcai; Sun, Peng; Bai, Xingwen; Ma, Youji; Zhang, Zhidong

    2016-02-01

    Foot-and-mouth disease is a highly contagious, acute viral disease of cloven-hoofed animal species causing severe economic losses worldwide. Among the seven serotypes of foot-and-mouth disease virus (FMDV), serotype O is predominant, but its viral capsid is more acid sensitive than other serotypes, making it more difficult to produce empty serotype O VLPs in the low pH insect hemolymph. Therefore, a novel chimeric virus-like particle (VLP)-based candidate vaccine for serotype O FMDV was developed and characterized in the present study. The chimeric VLPs were composed of antigenic VP1 from serotype O and segments of viral capsid proteins from serotype Asia1. These VLPs elicited significantly higher FMDV-specific antibody levels in immunized mice than did the inactivated vaccine. Furthermore, the chimeric VLPs protected guinea pigs from FMDV challenge with an efficacy similar to that of the inactivated vaccine. These results suggest that chimeric VLPs have the potential for use in vaccines against serotype O FMDV infection.

  8. Vaccination with recombinant adenoviruses expressing the peste des petits ruminants virus F or H proteins overcomes viral immunosuppression and induces protective immunity against PPRV challenge in sheep.

    Directory of Open Access Journals (Sweden)

    José M Rojas

    Full Text Available Peste des petits ruminants (PPR is a highly contagious disease of small ruminants caused by the Morbillivirus peste des petits ruminants virus (PPRV. Two recombinant replication-defective human adenoviruses serotype 5 (Ad5 expressing either the highly immunogenic fusion protein (F or hemagglutinin protein (H from PPRV were used to vaccinate sheep by intramuscular inoculation. Both recombinant adenovirus vaccines elicited PPRV-specific B- and T-cell responses. Thus, neutralizing antibodies were detected in sera from immunized sheep. In addition, we detected a significant antigen specific T-cell response in vaccinated sheep against two different PPRV strains, indicating that the vaccine induced heterologous T cell responses. Importantly, no clinical signs and undetectable virus shedding were observed after virulent PPRV challenge in vaccinated sheep. These vaccines also overcame the T cell immunosuppression induced by PPRV in control animals. The results indicate that these adenovirus constructs could be a promising alternative to current vaccine strategies for the development of PPRV DIVA vaccines.

  9. Immunological response to parenteral vaccination with recombinant hepatitis B virus surface antigen virus-like particles expressing Helicobacter pylori KatA epitopes in a murine H. pylori challenge model.

    Science.gov (United States)

    Kotiw, Michael; Johnson, Megan; Pandey, Manisha; Fry, Scott; Hazell, Stuart L; Netter, Hans J; Good, Michael F; Olive, Colleen

    2012-02-01

    Virus-like particles (VLPs) based on the small envelope protein of hepatitis B virus (HBsAg-S) are immunogenic at the B- and T-cell level. In this study, we inserted overlapping sequences encoding the carboxy terminus of the Helicobacter pylori katA gene product into HBsAg-S. The HBsAg-S-KatA fusion proteins were able to assemble into secretion-competent VLPs (VLP-KatA). The VLP-KatA proteins were able to induce KatA-specific antibodies in immunized mice. The mean total IgG antibody titers 41 days post-primary immunization with VLP-KatA (2.3 × 10(3)) were significantly greater (P < 0.05) than those observed for vaccination with VLP alone (5.2 × 10(2)). Measurement of IgG isotypes revealed responses to both IgG1 and IgG2a (mean titers, 9.0 × 10(4) and 2.6 × 10(4), respectively), with the IgG2a response to vaccination with VLP-KatA being significantly higher than that for mice immunized with KatA alone (P < 0.05). Following challenge of mice with H. pylori, a significantly reduced bacterial load in the gastric mucosa was observed (P < 0.05). This is the first report describing the use of VLPs as a delivery vehicle for H. pylori antigens.

  10. Antibody-mediated protection against mucosal simian-human immunodeficiency virus challenge of macaques immunized with alphavirus replicon particles and boosted with trimeric envelope glycoprotein in MF59 adjuvant.

    Science.gov (United States)

    Barnett, Susan W; Burke, Brian; Sun, Yide; Kan, Elaine; Legg, Harold; Lian, Ying; Bost, Kristen; Zhou, Fengmin; Goodsell, Amanda; Zur Megede, Jan; Polo, John; Donnelly, John; Ulmer, Jeffrey; Otten, Gillis R; Miller, Christopher J; Vajdy, Michael; Srivastava, Indresh K

    2010-06-01

    We have previously shown that rhesus macaques were partially protected against high-dose intravenous challenge with simian-human immunodeficiency virus SHIV(SF162P4) following sequential immunization with alphavirus replicon particles (VRP) of a chimeric recombinant VEE/SIN alphavirus (derived from Venezuelan equine encephalitis virus [VEE] and the Sindbis virus [SIN]) encoding human immunodeficiency virus type 1 HIV-1(SF162) gp140DeltaV2 envelope (Env) and trimeric Env protein in MF59 adjuvant (R. Xu, I. K. Srivastava, C. E. Greer, I. Zarkikh, Z. Kraft, L. Kuller, J. M. Polo, S. W. Barnett, and L. Stamatatos, AIDS Res. Hum. Retroviruses 22:1022-1030, 2006). The protection did not require T-cell immune responses directed toward simian immunodeficiency virus (SIV) Gag. We extend those findings here to demonstrate antibody-mediated protection against mucosal challenge in macaques using prime-boost regimens incorporating both intramuscular and mucosal routes of delivery. The macaques in the vaccination groups were primed with VRP and then boosted with Env protein in MF59 adjuvant, or they were given VRP intramuscular immunizations alone and then challenged with SHIV(SF162P4) (intrarectal challenge). The results demonstrated that these vaccines were able to effectively protect the macaques to different degrees against subsequent mucosal SHIV challenge, but most noteworthy, all macaques that received the intramuscular VRP prime plus Env protein boost were completely protected. A statistically significant association was observed between the titer of virus neutralizing and binding antibodies as well as the avidity of anti-Env antibodies measured prechallenge and protection from infection. These results highlight the merit of the alphavirus replicon vector prime plus Env protein boost vaccine approach for the induction of protective antibody responses and are of particular relevance to advancing our understanding of the potential correlates of immune protection against

  11. Adsorption of recombinant poxvirus L1-protein to aluminum hydroxide/CpG vaccine adjuvants enhances immune responses and protection of mice from vaccinia virus challenge.

    Science.gov (United States)

    Xiao, Yuhong; Zeng, Yuhong; Alexander, Edward; Mehta, Shyam; Joshi, Sangeeta B; Buchman, George W; Volkin, David B; Middaugh, C Russell; Isaacs, Stuart N

    2013-01-02

    The stockpiling of live vaccinia virus vaccines has enhanced biopreparedness against the intentional or accidental release of smallpox. Ongoing research on future generation smallpox vaccines is providing key insights into protective immune responses as well as important information about subunit-vaccine design strategies. For protein-based recombinant subunit vaccines, the formulation and stability of candidate antigens with different adjuvants are important factors to consider for vaccine design. In this work, a non-tagged secreted L1-protein, a target antigen on mature virus, was expressed using recombinant baculovirus technology and purified. To identify optimal formulation conditions for L1, a series of biophysical studies was performed over a range of pH and temperature conditions. The overall physical stability profile was summarized in an empirical phase diagram. Another critical question to address for development of an adjuvanted vaccine was if immunogenicity and protection could be affected by the interactions and binding of L1 to aluminum salts (Alhydrogel) with and without a second adjuvant, CpG. We thus designed a series of vaccine formulations with different binding interactions between the L1 and the two adjuvants, and then performed a series of vaccination-challenge experiments in mice including measurement of antibody responses and post-challenge weight loss and survival. We found that better humoral responses and protection were conferred with vaccine formulations when the L1-protein was adsorbed to Alhydrogel. These data demonstrate that designing vaccine formulation conditions to maximize antigen-adjuvant interactions is a key factor in smallpox subunit-vaccine immunogenicity and protection.

  12. Protective efficacy of Marek's disease virus (MDV) CVI-988 CEF65 clone C against challenge infection with three very virulent MDV strains.

    Science.gov (United States)

    de Boer, G F; Groenendal, J E; Boerrigter, H M; Kok, G L; Pol, J M

    1986-01-01

    Comparative 50% protective dose (PD50) assays were performed using a plaque-purified preparation of Marek's disease virus (MDV) strain CVI-988 at the 65th chicken embryo fibroblast (CEF) passage level (MDV CVI-988 CEF65 clone C) and three commercial MD vaccines: herpesvirus of turkeys (HVT) FC126, MDV CVI-988 CEF35, and a bivalent vaccine composed of HVT FC126 and MDV SB-1. In addition, comparative PD50 assays were performed in groups of chickens with maternal antibody to each of the three vaccines. Three representatives of the newly emerged biovariant very virulent (vv) MDV strains-RB/1B, Tun, and Md5-were employed as challenge virus. The experiments made feasible the differentiation between virulent MDV and vvMDV strains, within serotype 1. Vaccination with CVI-988 clone C vaccine resulted in PD50 estimates of about 5 plaque-forming units (PFUs) against challenge infection with each of the three vvMDV strains. The PD50 estimate of CVI-988 clone C vaccine was 12-fold below the PD50 of HVT FC126. The protective synergism of bivalent vaccine, composed of HVT and SB-1, was confirmed by groups given the lowest vaccine doses. The bivalent vaccine, however, resulted in incomplete protection in groups given the highest vaccine doses. Homologous maternal antibodies to serotype 1 caused a fivefold increase in the PD50 estimate of CVI-988 clone C. Heterologous maternal antibodies against HVT did not interfere with efficacy of CVI-988 clone C vaccination. However, the combination of maternal antibodies against both HVT and SB-1 (serotypes 2 and 3) showed a strong adverse effect on CVI-988 clone C vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Informing the Historical Record of Experimental Nonhuman Primate Infections with Ebola Virus: Genomic Characterization of USAMRIID Ebola Virus/H.sapiens-tc/COD/1995/Kikwit-9510621 Challenge Stock R4368 and Its Replacement R4415

    Science.gov (United States)

    2016-03-20

    Lefkowitz EJ, editors. Virus Taxonomy - 8 Ninth Report of the International Committee on Taxonomy of Viruses . London, UK: 9 Elsevier/Academic Press...Ebola virus variants that emerged in Guinea and the 16 Democratic Republic of the Congo in 2014. Viruses . 2014;6(11):4760-99. doi: 17 10.3390/v6114760...1 Informing the historical record of experimental nonhuman primate 1 infections with Ebola virus : genomic characterization of 2 USAMRIID Ebola

  14. Differential expression of small non-coding RNAs in serum from cattle challenged with viruses causing bovine respiratory disease

    Science.gov (United States)

    MicroRNAs and tRNA-derived RNA fragments (tRFs) are the two most abundant groups of small non-coding RNAs. The potential for microRNAs and tRFs to be used as pathogen exposure indicators is yet to be fully explored. Our objective was to identify microRNAs and tRFs in cattle challenged with a non-cy...

  15. Protective efficacy of recombinant and inactivated H5 avian influenza vaccines against challenge from the 2014 intercontinental H5 highly pathogenic avian influenza viruses (H5N8 and H5N2)

    Science.gov (United States)

    Protective immunity against highly pathogenic avian influenza (HPAI) largely depends on the development of an antibody response against a specific subtype of challenge virus. Historically, the use of antigenically closely matched isolates has proven efficacious when used as inactivated vaccines. M...

  16. Correction: Forrester, N.L.; Coffey, L.L.; Weaver, S.C. Arboviral Bottlenecks and Challenges to Maintaining Diversity and Fitness during Mosquito Transmission. Viruses 2014, 6, 3991–4004

    Directory of Open Access Journals (Sweden)

    Naomi L. Forrester

    2014-11-01

    Full Text Available In the original manuscript, Forrester, N.L.; Coffey, L.L.; Weaver, S.C. Arboviral Bottlenecks and Challenges to Maintaining Diversity and Fitness during Mosquito Transmission. Viruses 2014, 6, 3991–4004, Figure 1 contains an error, the third bottle was absent from the figure:[...

  17. Antibodies specific for hypervariable regions 3 to 5 of the feline immunodeficiency virus envelope glycoprotein are not solely responsible for vaccine-induced acceleration of challenge infection in cats

    NARCIS (Netherlands)

    W. Huisman (Willem); E.J.A. Schrauwen (Eefje); S.D. Pas (Suzan); J.A. Karlas (Jos); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

    2004-01-01

    textabstractIn a previous vaccination study in cats, the authors reported on accelerated feline immunodeficiency virus (FIV) replication upon challenge in animals vaccinated with a candidate envelope subunit vaccine. Plasma transfer studies as well as antibody profiles in vaccinated cats indicated a

  18. Examination of influenza specific T cell responses after influenza virus challenge in individuals vaccinated with MVA-NP+M1 vaccine.

    Directory of Open Access Journals (Sweden)

    Timothy J Powell

    Full Text Available Current influenza vaccines stimulate neutralising antibody to the haemagglutinin antigen but as there is antigenic drift in HA it is difficult to prepare a vaccine in advance against an emergent strain. A potential strategy is to induce CD8(+ and CD4(+ T cells that recognize epitopes within internal proteins that are less subject to antigenic drift. Augmenting humoral responses to HA with T cell responses to more conserved antigens may result in a more broadly protective vaccine. In this study, we evaluate the quality of influenza specific T cell responses in a clinical trial using MVA-NP+M1 vaccination followed by influenza virus challenge. In vaccinated volunteers, the expression of Granzyme A, Perforin and CD57 on influenza HLA A*02 M158-66 antigen specific cells was higher than non-vaccinated volunteers before and after challenge despite a similar frequency of antigen specific cells. BCL2 expression was lower in vaccinated volunteers. These data indicate that antigen specific T cells are a useful additional measure for use in human vaccination or immunization studies.

  19. Evaluating the Orthopoxvirus Type I Interferon-Binding Molecule as a Vaccine Target in the Vaccinia Virus Intranasal Murine Challenge Model ▿

    Science.gov (United States)

    Golden, Joseph W.; Hooper, Jay W.

    2010-01-01

    The biological threat imposed by orthopoxviruses warrants the development of safe and effective vaccines. We developed a candidate orthopoxvirus DNA-based vaccine, termed 4pox, which targets four viral structural components, A33, B5, A27, and L1. While this vaccine protects mice and nonhuman primates from lethal infections, we are interested in further enhancing its potency. One approach to enhance potency is to include additional orthopoxvirus immunogens. Here, we investigated whether vaccination with the vaccinia virus (VACV) interferon (IFN)-binding molecule (IBM) could protect BALB/c mice against lethal VACV challenge. We found that vaccination with this molecule failed to significantly protect mice from VACV when delivered alone. IBM modestly augmented protection when delivered together with the 4pox vaccine. All animals receiving the 4pox vaccine plus IBM lived, whereas only 70% of those receiving a single dose of 4pox vaccine survived. Mapping studies using truncated mutants revealed that vaccine-generated antibodies spanned the immunoglobulin superfamily domains 1 and 2 and, to a lesser extent, 3 of the IBM. These antibodies inhibited IBM cell binding and IFN neutralization activity, indicating that they were functionally active. This study shows that DNA vaccination with the VACV IBM results in a robust immune response but that this response does not significantly enhance protection in a high-dose challenge model. PMID:20844086

  20. Targeting the non-structural protein 1 from dengue virus to a dendritic cell population confers protective immunity to lethal virus challenge.

    Science.gov (United States)

    Henriques, Hugo R; Rampazo, Eline V; Gonçalves, Antonio J S; Vicentin, Elaine C M; Amorim, Jaime H; Panatieri, Raquel H; Amorim, Kelly N S; Yamamoto, Marcio M; Ferreira, Luís C S; Alves, Ada M B; Boscardin, Silvia B

    2013-01-01

    Dengue is the most prevalent arboviral infection, affecting millions of people every year. Attempts to control such infection are being made, and the development of a vaccine is a World Health Organization priority. Among the proteins being tested as vaccine candidates in preclinical settings is the non-structural protein 1 (NS1). In the present study, we tested the immune responses generated by targeting the NS1 protein to two different dendritic cell populations. Dendritic cells (DCs) are important antigen presenting cells, and targeting proteins to maturing DCs has proved to be an efficient means of immunization. Antigen targeting is accomplished by the use of a monoclonal antibody (mAb) directed against a DC cell surface receptor fused to the protein of interest. We used two mAbs (αDEC205 and αDCIR2) to target two distinct DC populations, expressing either DEC205 or DCIR2 endocytic receptors, respectively, in mice. The fusion mAbs were successfully produced, bound to their respective receptors, and were used to immunize BALB/c mice in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C)), as a DC maturation stimulus. We observed induction of strong anti-NS1 antibody responses and similar antigen binding affinity irrespectively of the DC population targeted. Nevertheless, the IgG1/IgG2a ratios were different between mouse groups immunized with αDEC-NS1 and αDCIR2-NS1 mAbs. When we tested the induction of cellular immune responses, the number of IFN-γ producing cells was higher in αDEC-NS1 immunized animals. In addition, mice immunized with the αDEC-NS1 mAb were significantly protected from a lethal intracranial challenge with the DENV2 NGC strain when compared to mice immunized with αDCIR2-NS1 mAb. Protection was partially mediated by CD4(+) and CD8(+) T cells as depletion of these populations reduced both survival and morbidity signs. We conclude that targeting the NS1 protein to the DEC205(+) DC population with poly (I:C) opens

  1. Targeting the non-structural protein 1 from dengue virus to a dendritic cell population confers protective immunity to lethal virus challenge.

    Directory of Open Access Journals (Sweden)

    Hugo R Henriques

    Full Text Available Dengue is the most prevalent arboviral infection, affecting millions of people every year. Attempts to control such infection are being made, and the development of a vaccine is a World Health Organization priority. Among the proteins being tested as vaccine candidates in preclinical settings is the non-structural protein 1 (NS1. In the present study, we tested the immune responses generated by targeting the NS1 protein to two different dendritic cell populations. Dendritic cells (DCs are important antigen presenting cells, and targeting proteins to maturing DCs has proved to be an efficient means of immunization. Antigen targeting is accomplished by the use of a monoclonal antibody (mAb directed against a DC cell surface receptor fused to the protein of interest. We used two mAbs (αDEC205 and αDCIR2 to target two distinct DC populations, expressing either DEC205 or DCIR2 endocytic receptors, respectively, in mice. The fusion mAbs were successfully produced, bound to their respective receptors, and were used to immunize BALB/c mice in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C, as a DC maturation stimulus. We observed induction of strong anti-NS1 antibody responses and similar antigen binding affinity irrespectively of the DC population targeted. Nevertheless, the IgG1/IgG2a ratios were different between mouse groups immunized with αDEC-NS1 and αDCIR2-NS1 mAbs. When we tested the induction of cellular immune responses, the number of IFN-γ producing cells was higher in αDEC-NS1 immunized animals. In addition, mice immunized with the αDEC-NS1 mAb were significantly protected from a lethal intracranial challenge with the DENV2 NGC strain when compared to mice immunized with αDCIR2-NS1 mAb. Protection was partially mediated by CD4(+ and CD8(+ T cells as depletion of these populations reduced both survival and morbidity signs. We conclude that targeting the NS1 protein to the DEC205(+ DC population with poly (I

  2. Hepatitis C virus reinfection after liver transplant: New chances and new challenges in the era of direct-actingantiviral agents

    Institute of Scientific and Technical Information of China (English)

    Kerstin Herzer; Guido Gerken

    2015-01-01

    The first interferon-free regimens have been approvedfor the treatment of patients with chronic hepatitisC virus (HCV). In the liver transplant (LT) setting,these regimens are expected to have an importanteffect, because graft loss due to HCV recurrenceis aserious problem after LT. The response to the hithertoconventional treatment with pegylated interferon andribavirin is poor. The significantly better responserates achieved with boceprevir-based and telaprevirbasedtriple therapy have led to better graft andpatient survival rates, but severe drug interactionswith immunosuppressants limit the feasibility of thistherapy for LT patients. With the approval of sofosbuvirin January 2014, of simeprevir in May 2014, and ofdaclatasvir in August 2014, three antiviral agents arenow available and promise to be applicable withoutrelevant adverse effects or negative interactions withimmunosuppressants. Thus, 2014 marks the beginningof a new era of treatment options for HCV recurrenceafter LT. Although safety and efficacy studies of severalinterferon-free regimens for patients with HCVrecurrence after LT have achieved good preliminaryresults, reports of clinical experiences with LT patientsare scarce. The lack of randomized studies, the smallnumber of enrolled and carefully selected patients, andthe heterogeneity of these studies make the resultsquestionable. Real-life experiences are eagerly awaitedso that clinicians can estimate the usefulness and thepitfalls of these new regimens. Additionally, the highcosts of these agents may limit their accessibility formany patients. The aim of this review is to summarizethe current experience with and the expectations of thenew direct-acting antiviral agents for LT patients.

  3. Gene expression and functional studies of small heat shock protein 37 (MrHSP37) from Macrobrachium rosenbergii challenged with infectious hypodermal and hematopoietic necrosis virus (IHHNV).

    Science.gov (United States)

    Arockiaraj, Jesu; Vanaraja, Puganeshwaran; Easwvaran, Sarasvathi; Singh, Arun; Othman, Rofina Yasmin; Bhassu, Subha

    2012-06-01

    In this study, we have reported a full length of small heat shock protein 37 (designated MrHSP37) gene, identified from the transcriptome database of freshwater prawn Macrobrachium rosenbergii. The complete gene sequence of the MrHSP37 is 2,425 base pairs in length, and encodes 338 amino acids. MrHSP37 contains a long heat shock protein family profile in the amino acid sequence between 205 and 288. The mRNA expressions of MrHSP37 in healthy and the infectious hypodermal and hematopoietic necrosis virus (IHHNV) challenged M. rosenbergii were examined using quantitative real time polymerase chain reaction (qRT-PCR). MrHSP37 is highly expressed in hepatopancreas and all the other tissues (walking leg, gills, muscle, stomach, haemocyte, intestine, pleopods, brain and eye stalk) of M. rosenbergii taken for analysis. The expression is strongly up-regulated after IHHNV challenge. To understand its biological activity, the recombinant MrHSP37 gene was constructed and expressed in Escherichia coli BL21 (DE3). The results of ATPase assay showed that the recombinant MrHSP37 protein exhibited apparent ATPase activity which increased with the concentration of the protein. And also the purified recombinant MrHSP37 protein was used for thermal aggregation assay (chaperone activity). It showed that the recombinant MrHSP37 protein is an active chaperone in this assay. Taken together, these results suggest that MrHSP37 is potentially involved in the immune responses against IHHNV challenge in M. rosenbergii.

  4. Infectious bursal disease: evaluation of maternal immunity and protection by vaccination of one-day old chicks against challenge with a very virulent virus isolate

    Directory of Open Access Journals (Sweden)

    HLS Moraes

    2005-03-01

    Full Text Available Broiler chicks belonging to two poultry companies, A and B, with different breeders' vaccination programs were challenged with a very virulent strains of infectious bursal disease virus (vvIBDV, genotyped as G11. Birds were separated in four groups, two vaccinated at the first day of life and two unvaccinated. They were then challenged at the 1st, 4th, 7th, 10th, 13th, 16th, 19th and 22nd days. At every day of challenge, before and after the procedure, the following data were collected from each group: Bursa of Fabricius (BF relative weight, BF diameter, BF for histologie examination, serum for measuring antibodies against IBDV through the ELISA and clinical evaluation of IBD. The results obtained have shown a non-significant drop in antibody level between the vaccinated and the unvaccinated groups. When analyzing the different results, it could be established that an ELISA titre of 3,4 log10 was the cutoff point between healthy and sick birds. Regression equations were built to determinate the best moment for vaccination and also the ELISA log titre birds what could present in a given age. Based on that, chicks from Company A should receive a vaccine against IBD from the 6th to 7th day of age, while the ones from Company B should get it between the 11th and the 12th day of age. Finally, the overall results suggest that the birds should not be vaccinated at one day old, and also that the breeders' different vaccination schemes resulted in progenies with different levels of maternal protection, and as a consequence the same vaccination plan should not be applied indiscriminately to broilers from different poultry companies.

  5. Co-expression of Erns and E2 genes of classical swine fever virus by replication-defective recombinant adenovirus completely protects pigs against virulent challenge with classical swine fever virus.

    Science.gov (United States)

    Sun, Yongke; Yang, Yuai; Zheng, Huanli; Xi, Dongmei; Lin, Mingxing; Zhang, Xiaomin; Yang, Linfu; Yan, Yulin; Chu, Xiaohui; Bi, Baoliang

    2013-04-01

    The objective of this study was to construct a recombinant adenovirus for future CSFV vaccines used in the pig industry for the reduction of losses involved in CSF outbreaks. The Erns and E2 genes of classical swine fever virus (CSFV), which encode the two main protective glycoproteins from the "Shimen" strain of CSFV, were combined and inserted into the replication-defective human adenovirus type-5 and named the rAd-Erns-E2. Nine pigs were randomly assigned to three treatment groups (three pigs in each group) including the rAd-Erns-E2, hAd-CMV control and DMEM control. Intramuscular vaccination with 2×10(6) TCID(50) of the rAd-Erns-E2 was administered two times with an interval of 21 days. At 42 days post inoculation, pigs in all groups were challenged with a lethal dose of 1×10(3) TCID(50) CSFV "Shimen" strain. Observation of clinical signs was made and the existence of CSFV RNA was detected. Animals in the hAd-CMV and DMEM groups showed severe clinical CSF symptoms and were euthanized from 7 to 10 days after the challenge. However, no adverse clinical CSF signs were observed in vaccinated pigs after the administration of rAd-Erns-E2 and even after CSFV challenge. Neither CSFV RNA nor pathological changes were detected in the tissues of interest of the above vaccinated pigs. These results implied that the recombination adenovirus carrying the Erns-E2 genes could be used to prevent swine from classical swine fever.

  6. Influenza virus-like particles produced by transient expression in Nicotiana benthamiana induce a protective immune response against a lethal viral challenge in mice.

    Science.gov (United States)

    D'Aoust, Marc-André; Lavoie, Pierre-Olivier; Couture, Manon M-J; Trépanier, Sonia; Guay, Jean-Martin; Dargis, Michèle; Mongrand, Sébastien; Landry, Nathalie; Ward, Brian J; Vézina, Louis-P

    2008-12-01

    A strain-specific vaccine represents the best possible response to the threat of an influenza pandemic. Rapid delivery of such a vaccine to the world's population before the peak of the first infection wave seems to be an unattainable goal with the current influenza vaccine manufacturing capacity. Plant-based transient expression is one of the few production systems that can meet the anticipated surge requirement. To assess the capability of plant agroinfiltration to produce an influenza vaccine, we expressed haemagglutinin (HA) from strains A/Indonesia/5/05 (H5N1) and A/New Caledonia/20/99 (H1N1) by agroinfiltration of Nicotiana benthamiana plants. Size distribution analysis of protein content in infiltrated leaves revealed that HA was predominantly assembled into high-molecular-weight structures. H5-containing structures were purified and examination by transmission electron microscopy confirmed virus-like particle (VLP) assembly. High-performance thin layer chromatography analysis of VLP lipid composition highlighted polar and neutral lipid contents comparable with those of purified plasma membranes from tobacco plants. Electron microscopy of VLP-producing cells in N. benthamiana leaves confirmed that VLPs accumulated in apoplastic indentations of the plasma membrane. Finally, immunization of mice with two doses of as little as 0.1 microg of purified influenza H5-VLPs triggered a strong immune response against the homologous virus, whereas two doses of 0.5 microg of H5-VLPs conferred complete protection against a lethal challenge with the heterologous A/Vietnam/1194/04 (H5N1) strain. These results show, for the first time, that plants are capable of producing enveloped influenza VLPs budding from the plasma membrane; such VLPs represent very promising candidates for vaccination against influenza pandemic strains.

  7. Learning from Experience: The Public Health Response to West Nile Virus, SARS, Monkeypox, and Hepatitis A Outbreaks in the United States

    Science.gov (United States)

    2005-01-01

    water Identify potential cases; Isolation of suspected cases; Contact tracing (critical to containment) Isolation of cases; Isolation/ euthanasia ...department also fielded phone calls from the worried well (e.g., businesses and universities with personnel who had recently returned from overseas

  8. Role of the DNA Sensor STING in Protection from Lethal Infection following Corneal and Intracerebral Challenge with Herpes Simplex Virus 1.

    Science.gov (United States)

    Parker, Zachary M; Murphy, Aisling A; Leib, David A

    2015-11-01

    STING is a protein in the cytosolic DNA and cyclic dinucleotide sensor pathway that is critical for the initiation of innate responses to infection by various pathogens. Consistent with this, herpes simplex virus 1 (HSV-1) causes invariable and rapid lethality in STING-deficient (STING(-/-)) mice following intravenous (i.v.) infection. In this study, using real-time bioluminescence imaging and virological assays, as expected, we demonstrated that STING(-/-) mice support greater replication and spread in ocular tissues and the nervous system. In contrast, they did not succumb to challenge via the corneal route even with high titers of a virus that was routinely lethal to STING(-/-) mice by the i.v. route. Corneally infected STING(-/-) mice also showed increased periocular disease and increased corneal and trigeminal ganglia titers, although there was no difference in brain titers. They also showed elevated expression of tumor necrosis factor alpha (TNF-α) and CXCL9 relative to control mice but surprisingly modest changes in type I interferon expression. Finally, we also showed that HSV strains lacking the ability to counter autophagy and the PKR-driven antiviral state had near-wild-type virulence following intracerebral infection of STING(-/-) mice. Together, these data show that while STING is an important component of host resistance to HSV in the cornea, its previously shown immutable role in mediating host survival by the i.v. route was not recapitulated following a mucosal infection route. Furthermore, our data are consistent with the idea that HSV counters STING-mediated induction of the antiviral state and autophagy response, both of which are critical factors for survival following direct infection of the nervous system. HSV infections represent an incurable source of morbidity and mortality in humans and are especially severe in neonatal and immunocompromised populations. A key step in the development of an immune response is the recognition of microbial

  9. Identification of viral epitopes recognized by the immune system following vaccination and challenge with the H7N9 avian influenza virus from China

    Science.gov (United States)

    In March of 2013, the first cases of H7N9 influenza were reported in humans in China, and shortly thereafter the virus was confirmed from poultry in live bird markets. Since that time the virus has persisted in both human and avian populations. The genetic composition of these H7N9 influenza virus...

  10. Optimisations and Challenges Involved in the Creation of Various Bioluminescent and Fluorescent Influenza A Virus Strains for In Vitro and In Vivo Applications.

    Science.gov (United States)

    Spronken, Monique I; Short, Kirsty R; Herfst, Sander; Bestebroer, Theo M; Vaes, Vincent P; van der Hoeven, Barbara; Koster, Abraham J; Kremers, Gert-Jan; Scott, Dana P; Gultyaev, Alexander P; Sorell, Erin M; de Graaf, Miranda; Bárcena, Montserrat; Rimmelzwaan, Guus F; Fouchier, Ron A

    2015-01-01

    Bioluminescent and fluorescent influenza A viruses offer new opportunities to study influenza virus replication, tropism and pathogenesis. To date, several influenza A reporter viruses have been described. These strategies typically focused on a single reporter gene (either bioluminescent or fluorescent) in a single virus backbone. However, whilst bioluminescence is suited to in vivo imaging, fluorescent viruses are more appropriate for microscopy. Therefore, the idea l reporter virus varies depending on the experiment in question, and it is important that any reporter virus strategy can be adapted accordingly. Herein, a strategy was developed to create five different reporter viruses in a single virus backbone. Specifically, enhanced green fluorescent protein (eGFP), far-red fluorescent protein (fRFP), near-infrared fluorescent protein (iRFP), Gaussia luciferase (gLUC) and firefly luciferase (fLUC) were inserted into the PA gene segment of A/PR/8/34 (H1N1). This study provides a comprehensive characterisation of the effects of different reporter genes on influenza virus replication and reporter activity. In vivo reporter gene expression, in lung tissues, was only detected for eGFP, fRFP and gLUC expressing viruses. In vitro, the eGFP-expressing virus displayed the best reporter stability and could be used for correlative light electron microscopy (CLEM). This strategy was then used to create eGFP-expressing viruses consisting entirely of pandemic H1N1, highly pathogenic avian influenza (HPAI) H5N1 and H7N9. The HPAI H5N1 eGFP-expressing virus infected mice and reporter gene expression was detected, in lung tissues, in vivo. Thus, this study provides new tools and insights for the creation of bioluminescent and fluorescent influenza A reporter viruses.

  11. Optimisations and Challenges Involved in the Creation of Various Bioluminescent and Fluorescent Influenza A Virus Strains for In Vitro and In Vivo Applications

    Science.gov (United States)

    Herfst, Sander; Bestebroer, Theo M.; Vaes, Vincent P.; van der Hoeven, Barbara; Koster, Abraham J.; Kremers, Gert-Jan; Scott, Dana P.; Gultyaev, Alexander P.; Sorell, Erin M.; de Graaf, Miranda; Bárcena, Montserrat; Rimmelzwaan, Guus F.; Fouchier, Ron A.

    2015-01-01

    Bioluminescent and fluorescent influenza A viruses offer new opportunities to study influenza virus replication, tropism and pathogenesis. To date, several influenza A reporter viruses have been described. These strategies typically focused on a single reporter gene (either bioluminescent or fluorescent) in a single virus backbone. However, whilst bioluminescence is suited to in vivo imaging, fluorescent viruses are more appropriate for microscopy. Therefore, the idea l reporter virus varies depending on the experiment in question, and it is important that any reporter virus strategy can be adapted accordingly. Herein, a strategy was developed to create five different reporter viruses in a single virus backbone. Specifically, enhanced green fluorescent protein (eGFP), far-red fluorescent protein (fRFP), near-infrared fluorescent protein (iRFP), Gaussia luciferase (gLUC) and firefly luciferase (fLUC) were inserted into the PA gene segment of A/PR/8/34 (H1N1). This study provides a comprehensive characterisation of the effects of different reporter genes on influenza virus replication and reporter activity. In vivo reporter gene expression, in lung tissues, was only detected for eGFP, fRFP and gLUC expressing viruses. In vitro, the eGFP-expressing virus displayed the best reporter stability and could be used for correlative light electron microscopy (CLEM). This strategy was then used to create eGFP-expressing viruses consisting entirely of pandemic H1N1, highly pathogenic avian influenza (HPAI) H5N1 and H7N9. The HPAI H5N1 eGFP-expressing virus infected mice and reporter gene expression was detected, in lung tissues, in vivo. Thus, this study provides new tools and insights for the creation of bioluminescent and fluorescent influenza A reporter viruses. PMID:26241861

  12. Co-administration of an adjuvanted FeLV vaccine together with a multivalent feline vaccine to cats is protective against virulent challenge with feline leukaemia virus, calicivirus, herpes virus and panleukopenia virus

    Directory of Open Access Journals (Sweden)

    Stephen Wilson

    2014-01-01

    In conclusion, the results from this study demonstrate that concurrent or simultaneous administration of these two vaccines resulted in equivalent efficacy; both vaccine administration regimes showing significant differences in clinical scores or lower levels of persistent antigenaemia when compared to non-vaccinated control cats following challenge.

  13. UV-inactivated vaccinia virus (VV) in a multi-envelope DNA-VV-protein (DVP) HIV-1 vaccine protects macaques from lethal challenge with heterologous SHIV

    Science.gov (United States)

    Jones, Bart G; Sealy, Robert E; Zhan, Xiaoyan; Freiden, Pamela J; Surman, Sherri L; Blanchard, James L.; Hurwitz, Julia L

    2012-01-01

    The pandemic of HIV-1 has continued for decades, yet there remains no licensed vaccine. Previous research has demonstrated the effectiveness of a multi-envelope, multi-vectored HIV-1 vaccine in a macaque-SHIV model, illustrating a potential means of combating HIV-1. Specifically, recombinant DNA, vaccinia virus (VV) and purified protein (DVP) delivery systems were used to vaccinate animals with dozens of antigenically-distinct HIV-1 envelopes for induction of immune breadth. The vaccinated animals controlled disease following challenge with a heterologous SHIV. This demonstration suggested that the antigenic cocktail vaccine strategy, which has succeeded in several other vaccine fields (e.g. pneumococcus), might also succeed against HIV-1. The strategy remains untested in an advanced clinical study, in part due to safety concerns associated with the use of replication-competent VV. To address this concern, we designed a macaque study in which psoralen/ultraviolet light-inactivated VV (UV VV) was substituted for replication-competent VV in the multi-envelope DVP protocol. Control animals received a vaccine encompassing no VV, or no vaccine. All VV vaccinated animals generated an immune response toward VV, and all vaccinated animals generated an immune response toward HIV-1 envelope. After challenge with heterologous SHIV 89.6P, animals that received replication-competent VV or UV VV experienced similar outcomes. They exhibited reduced peak viral loads, maintenance of CD4+ T cell counts and improved survival compared to control animals that received no VV or no vaccine; there were 0/15 deaths among all animals that received VV and 5/9 deaths among controls. Results define a practical means of improving VV safety, and encourage advancement of a promising multi-envelope DVP HIV-1 vaccine candidate. PMID:22425790

  14. A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus.

    Directory of Open Access Journals (Sweden)

    Sanchita Das

    Full Text Available CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR. The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively. The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus.

  15. A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus

    Science.gov (United States)

    Das, Sanchita; Rundell, Mark S.; Mirza, Aashiq H.; Pingle, Maneesh R.; Shigyo, Kristi; Garrison, Aura R.; Paragas, Jason; Smith, Scott K.; Olson, Victoria A.; Larone, Davise H.; Spitzer, Eric D.; Barany, Francis; Golightly, Linnie M.

    2015-01-01

    CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus). PMID:26381398

  16. Attenuated Salmonella typhimurium delivering DNA vaccine encoding duck enteritis virus UL24 induced systemic and mucosal immune responses and conferred good protection against challenge

    Directory of Open Access Journals (Sweden)

    Yu Xia

    2012-07-01

    Full Text Available Abstract Orally delivered DNA vaccines against duck enteritis virus (DEV were developed using live attenuated Salmonella typhimurium (SL7207 as a carrier and Escherichia coli heat labile enterotoxin B subunit (LTB as a mucosal adjuvant. DNA vaccine plasmids pVAX-UL24 and pVAX-LTB-UL24 were constructed and transformed into attenuated Salmonella typhimurium SL7207 resulting SL7207 (pVAX-UL24 and SL7207 (pVAX-LTB-UL24 respectively. After ducklings were orally inoculated with SL7207 (pVAX-UL24 or SL7207 (pVAX-LTB-UL24, the anti-DEV mucosal and systemic immune responses were recorded. To identify the optimum dose that confers maximum protection, we used different doses of the candidate vaccine SL7207 (pVAX-LTB-UL24 during oral immunization. The strongest mucosal and systemic immune responses developed in the SL7207 (pVAX-LTB-UL24 (1011 CFU immunized group. Accordingly, oral immunization of ducklings with SL7207 (pVAX-LTB-UL24 showed superior efficacy of protection (60-80% against a lethal DEV challenge (1000 LD50, compared with the limited survival rate (40% of ducklings immunized with SL7207 (pVAX-UL24. Our study suggests that the SL7207 (pVAX-LTB-UL24 can be a candidate DEV vaccine.

  17. Peritrophin-like protein from Litopenaeus vannamei (LvPT) involved in white spot syndrome virus (WSSV) infection in digestive tract challenged with reverse gavage

    Science.gov (United States)

    Xie, Shijun; Li, Fuhua; Zhang, Xiaojun; Zhang, Jiquan; Xiang, Jianhai

    2017-05-01

    The peritrophic membrane plays an important role in the defense system of the arthropod gut. The digestive tract is considered one of the major tissues targeted by white spot syndrome virus (WSSV) in shrimp. In this study, the nucleotide sequence encoding peritrophin-like protein of Litopenaeus vannamei (LvPT) was amplified from a yeast two-hybrid library of L. vannamei. The epitope peptide of LvPT was predicted with the GenScript OptimumAntigen™ design tool. An anti-LvPT polyclonal antibody was produced and shown to specifically bind a band at 27 kDa, identified as LvPT. The LvPT protein was expressed and its concentration determined. LvPT dsRNA (4 μg per shrimp) was used to inhibit LvPT expression in shrimp, and a WSSV challenge experiment was then performed with reverse gavage. The pleopods, stomachs, and guts were collected from the shrimp at 0, 24, 48, and 72 h post-infection (hpi). Viral load quantification showed that the levels of WSSV were significantly lower in the pleopods, stomachs, and guts of shrimp after LvPT dsRNA interference than in those of the controls at 48 and 72 hpi. Our results imply that LvPT plays an important role during WSSV infection of the digestive tract.

  18. Construction of a gE-Deleted Pseudorabies Virus and Its Efficacy to the New-Emerging Variant PRV Challenge in the Form of Killed Vaccine

    Directory of Open Access Journals (Sweden)

    Tongyan Wang

    2015-01-01

    Full Text Available The new-emerging PRV variants plague the vaccinated pigs and caused huge economic loss to local pig industry in China since 2011. The current commercial PRV vaccines cannot provide complete protection as the new-emerging PRV variants are antigenically different from the classical viruses. It is urgent to develop more safe and effective PRV vaccines based on the current circulating field isolates. In this study, a gE gene-deleted PRV based on the PRV HN1201, a representative PRV variant, was generated and the efficacy was tested on 3-week-old pigs in the form of killed vaccine. After fatal PRV HN1201 challenge, all vaccinated pigs survived without showing any clinical symptoms, but all unvaccinated pigs exhibited pseudorabies-specific respiratory and neurological signs with 100% mortality rate within 6 days after infection. The vaccinated pigs developed high level of gB and neutralizing antibodies after vaccination which may correlate to the protection provided by vaccine. Therefore, this gE gene-deleted PRV could be a promising vaccine candidate for the control of currently epidemic pseudorabies in China.

  19. Simulation-guided phase 3 trial design to evaluate vaccine effectiveness to prevent Ebola virus disease infection: Statistical considerations, design rationale, and challenges.

    Science.gov (United States)

    Vandebosch, An; Mogg, Robin; Goeyvaerts, Nele; Truyers, Carla; Greenwood, Brian; Watson-Jones, Debby; Herrera-Taracena, Guillermo; Parys, Wim; Vangeneugden, Tony

    2016-02-01

    Starting in December 2013, West Africa was overwhelmed with the deadliest outbreak of Ebola virus known to date, resulting in more than 27,500 cases and 11,000 deaths. In response to the epidemic, development of a heterologous prime-boost vaccine regimen was accelerated and involved preparation of a phase 3 effectiveness study. While individually randomized controlled trials are widely acknowledged as the gold standard for demonstrating the efficacy of a candidate vaccine, there was considerable debate on the ethical appropriateness of these designs in the context of an epidemic. A suitable phase 3 trial must convincingly ensure unbiased evaluation with sufficient statistical power. In addition, efficient evaluation of a vaccine candidate is required so that an effective vaccine can be immediately disseminated. This manuscript aims to present the statistical and modeling considerations, design rationale and challenges encountered due to the emergent, epidemic setting that led to the selection of a cluster-randomized phase 3 study design under field conditions.

  20. Induction of mucosal immune responses and protection of cattle against direct-contact challenge by intranasal delivery with foot-and-mouth disease virus antigen mediated by nanoparticles

    Directory of Open Access Journals (Sweden)

    Pan L

    2014-12-01

    Full Text Available Li Pan,1,2 Zhongwang Zhang,1,2 Jianliang Lv,1,2 Peng Zhou,1,2 Wenfa Hu,1,2 Yuzhen Fang,1,2 Haotai Chen,1,2 Xinsheng Liu,1,2 Junjun Shao,1,2 Furong Zhao,1,2 Yaozhong Ding,1,2 Tong Lin,1,2 Huiyun Chang,1,2 Jie Zhang,1,2 Yongguang Zhang,1,2 Yonglu Wang1,2 1State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS, Lanzhou, Gansu, People’s Republic of China; 2Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, People’s Republic of China Abstract: The aim of this study was to enhance specific mucosal, systemic, and cell-mediated immunity and to induce earlier onset of protection against direct-contact challenge in cattle by intranasal delivery of a nanoparticle-based nasal vaccine against type A foot-and-mouth disease (FMD. In this study, two kinds of nanoparticle-based nasal vaccines against type A FMD were designed: (1 chitosan-coated poly(lactic-co-glycolic acid (PLGA loaded with plasmid DNA (Chi-PLGA-DNA and (2 chitosan-trehalose and inactivated foot-and-mouth disease virus (FMDV (Chi-Tre-Inactivated. Cattle were immunized by an intranasal route with nanoparticles and then challenged for 48 hours by direct contact with two infected donor cattle per pen. Donors were inoculated intradermally in the tongue 48 hours before challenge, with 0.2 mL cattle-passaged FMDV. Serological and mucosal antibody responses were evaluated, and virus excretion and the number of contact infections were quantified. FMDV-specific secretory immunoglobulin (IgA (sIgA antibodies in nasal washes were initially detected at 4 days postvaccination (dpv with two kinds of nanoparticles. The highest levels of sIgA expression were observed in nasal washes, at 10 dpv, from animals with Chi-PLGA-DNA nanoparticles, followed by animals immunized once by intranasal route with

  1. Ebola Virus and Marburg Virus

    Science.gov (United States)

    Diseases and Conditions Ebola virus and Marburg virus By Mayo Clinic Staff Ebola virus and Marburg virus are related viruses that cause hemorrhagic ... Africa, where sporadic outbreaks have occurred for decades. Ebola virus and Marburg virus live in animal hosts, ...

  2. Ebola Virus and Marburg Virus

    Science.gov (United States)

    Ebola virus and Marburg virus Overview By Mayo Clinic Staff Ebola virus and Marburg virus are related viruses that ... Africa, where sporadic outbreaks have occurred for decades. Ebola virus and Marburg virus live in animal hosts, ...

  3. A Malaysia 97 monovalent foot-and-mouth disease vaccine (>6PD50/dose) protects pigs against challenge with a variant FMDV A SEA-97 lineage virus, 4 and 7 days post vaccination.

    Science.gov (United States)

    Nagendrakumar, Singanallur Balasubramanian; Hong, Nguyen Thi Thu; Geoffrey, Fosgate T; Jacqueline, Morris Michelle; Andrew, Davis; Michelle, Giles; Van Phuc, Kim; Ngon, Quach Vo; Phuong, Le Thi Thu; Phuc, Nguyen Ngoc Hong; Hanh, Tran Xuan; Van Hung, Vo; Quynhanh, Le Thi; Tan, Tran Minh; Long, Ngo Thanh; Wilna, Vosloo

    2015-08-26

    Pigs play a significant role during outbreaks of foot-and-mouth disease (FMD) due to their ability to amplify the virus. It is therefore essential to determine what role vaccination could play to prevent clinical disease and lower virus excretion into the environment. In this study we investigated the efficacy of the double oil emulsion A Malaysia 97 vaccine (>6PD50/dose) against heterologous challenge with an isolate belonging to the A SEA-97 lineage at 4 and 7 days post vaccination (dpv). In addition, we determined whether physical separation of pigs in the same room could prevent virus transmission. Statistically there was no difference in the level of protection offered by 4 and 7 dpv. However, no clinical disease or viral RNA was detected in the blood of pigs challenged 4 dpv, although three of the pigs had antibodies to the non-structural proteins (NSPs), indicating viral replication. Viral RNA was also detected in nasal and saliva swabs, but on very few occasions. Two of the pigs vaccinated seven days prior to challenge had vesicles distal from the injection site, but on the inoculated foot, and two pigs had viral RNA detected in the blood. One pig sero-converted to the NSPs. In contrast, all unvaccinated and inoculated pigs had evidence of infection. No infection occurred in any of the susceptible pigs in the same room, but separated from the infected pigs, indicating that strict biosecurity measures were sufficient under these experimental conditions to prevent virus transmission. However, viral RNA was detected in the nasal swabs of one group of pigs, but apparently not at sufficient levels to cause clinical disease. Vaccination led to a significant decrease in viral RNA in vaccinated pigs compared to unvaccinated and infected pigs, even with this heterologous challenge, and could therefore be considered as a control option during outbreaks.

  4. Efficacy of a Recombinant Turkey Herpesvirus H5 Vaccine Against Challenge With H5N1 Clades 1.1.2 and 2.3.2.1 Highly Pathogenic Avian Influenza Viruses in Domestic Ducks (Anas platyrhynchos domesticus).

    Science.gov (United States)

    Pantin-Jackwood, Mary J; Kapczynski, Darrell R; DeJesus, Eric; Costa-Hurtado, Mar; Dauphin, Gwenaelle; Tripodi, Astrid; Dunn, John R; Swayne, David E

    2016-03-01

    Domestic ducks are the second most abundant poultry species in many Asian countries and have played a critical role in the epizootiology of H5N1 highly pathogenic avian influenza (HPAI).In this study, the protective efficacy of a live recombinant vector vaccine based on a turkey herpesvirus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAI strain (A/Swan/Hungary/4999/ 2006) (rHVT-H5/2.2), given at 3 days of age, was examined in Pekin ducks (Anas platyrhynchos domesticus). The vaccine was given alone or in combination with an inactivated H5N1 clade 2.3.2.1 reverse genetic (rgGD/2.3.2.1) vaccine given at 16 days of age, either as a single vaccination or in a prime-boost regime. At 30 days of age, ducks were challenged with one of two H5N1 HPAI viruses: A/duck/Vietnam/NCVD-2721/2013 (clade 1.1.2) or A/duck/Vietnam/NCVD-1584/2012 (clade 2.3.2.1.C). These viruses produced 100% mortality in less than 5 days in nonvaccinated control ducks. Ducks vaccinated with the rgGD/2.3.2.1 vaccine, with or without the rHVT-H5/2.2 vaccine, were 90%-100% protected against mortality after challenge with either of the two H5N1 HPAI viruses. The rHVT-H5/2.2 vaccine alone, however, conferred only 30% protection against mortality after challenge with either H5N1 HPAI virus; the surviving ducks from these groups shed higher amount of virus and for longer than the single-vaccinated rgGD/2.3.2.1 group. Despite low protection, ducks vaccinated with the rHVT-H5/2.2 vaccine and challenged with the clade 1.1.2 Vietnam virus had a longer mean death time than nonvaccinated controls (P = 0.02). A booster effect was found on reduction of virus shedding when using both vaccines, with lower oropharyngeal viral titers at 4 days after challenge with either HPAI virus (P vaccine could be detected in samples collected from multiple tissues at different time points, indicting minimal levels of viral replication. In conclusion, although a minor effect on survival was observed, this study demonstrates

  5. Investigation of wild caught whitefish, Coregonus lavaretus (L.), for infection with viral haemorrhagic septicaemia virus (VHSV) and experimental challenge of whitefish with VHSV

    DEFF Research Database (Denmark)

    Skall, Helle Frank; Kjær, Torben Egil; Olesen, Niels Jørgen

    2004-01-01

    into contact with farmed rainbow trout. All samples were examined on cell cultures. No viruses were isolated. Three viral haemorrhagic septicaemia virus (VHSV) isolates of different origin were tested in infection trials by immersion and intraperitoneal (IP) injection, using 1.5 g farmed whitefish: an isolate...... in the spread of VHSV in Denmark is probably not significant. The experimental studies, however, showed that whitefish are potential carriers of VHSV as they suffer only low mortality after infection but continue to carry virus....

  6. Vaccination with a soluble recombinant hemagglutinin trimer protects pigs against a challenge with pandemic (H1N1) 2009 influenza virus to high titres

    NARCIS (Netherlands)

    Loeffen, W.L.A.; Vries, de R.P.; Stockhofe, N.; Zoelen-Bos, van D.J.; Maas, H.A.; Koch, G.; Moormann, R.J.M.; Rottier, P.J.M.; Haan, de C.A.M.

    2011-01-01

    In 2009 a new influenza A/H1N1 virus strain (“pandemic (H1N1) 2009”, H1N1v) emerged that rapidly spread around the world. The virus is suspected to have originated in swine through reassortment and to have subsequently crossed the species-barrier towards humans. Several cases of reintroduction into

  7. Low pathogenic avian influenza A(H7N9) virus causes high mortality in ferrets upon intratracheal challenge: a model to study intervention strategies.

    Science.gov (United States)

    Kreijtz, J H C M; Kroeze, E J B Veldhuis; Stittelaar, K J; de Waal, L; van Amerongen, G; van Trierum, S; van Run, P; Bestebroer, T; T Kuiken; Fouchier, R A M; Rimmelzwaan, G F; Osterhaus, A D M E

    2013-10-09

    Infections with low pathogenic avian influenza (LPAI) A(H7N9) viruses have caused more than 100 hospitalized human cases of severe influenza in China since February 2013 with a case fatality rate exceeding 25%. Most of these human infections presented with severe viral pneumonia, while limited information is available currently on the occurrence of mild and subclinical cases. In the present study, a ferret model for this virus infection in humans is presented to evaluate the pathogenesis of the infection in a mammalian host, as ferrets have been shown to mimic the pathogenesis of human infection with influenza viruses most closely. Ferrets were inoculated intratracheally with increasing doses (>10 e5 TCID50) of H7N9 influenza virus A/Anhui/1/2013 and were monitored for clinical and virological parameters up to four days post infection. Virus replication was detected in the upper and lower respiratory tracts while animals developed fatal viral pneumonia. This study illustrates the high pathogenicity of LPAI-H7N9 virus for mammals. Furthermore, the intratracheal inoculation route in ferrets proofs to offer a solid model for LPAI-H7N9 virus induced pneumonia in humans. This model will facilitate the development and assessment of clinical intervention strategies for LPAI-H7N9 virus infection in humans, such as preventive vaccination and the use of antivirals.

  8. Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models

    DEFF Research Database (Denmark)

    Bukh, Jens; Meuleman, Philip; Tellier, Raymond

    2010-01-01

    Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1-6 and determined the infectivity titer of acute-phase plasma pools in additional a...

  9. A Herpes Simplex Virus 2 (HSV-2) gD Mutant Impaired for Neural Tropism Is Superior to an HSV-2 gD Subunit Vaccine To Protect Animals from Challenge with HSV-2

    Science.gov (United States)

    Goodman, Kyle N.; Li, Daniel Y.; Raffeld, Mark; Chavez, Mayra

    2015-01-01

    ABSTRACT A recent phase 3 trial with soluble herpes simplex virus 2 (HSV-2) glycoprotein D (gD2t) in adjuvant failed to show protection against genital herpes. We postulated that live attenuated HSV-2 would provide more HSV antigens for induction of virus-specific antibodies and cellular immunity than would gD2t. We previously reported an HSV-2 mutant, HSV2-gD27, in which the nectin-1 binding domain of gD2 is altered so that the virus is impaired for infecting neural cells, but not epithelial cells, in vitro and is impaired for infecting dorsal root ganglia in mice (K. Wang, J. D. Kappel, C. Canders, W. F. Davila, D. Sayre, M. Chavez, L. Pesnicak, and J. I. Cohen, J Virol 86:12891–12902, 2012, doi:10.1128/JVI.01055-12). Here we report that the mutations in HSV2-gD27 were stable when the virus was passaged in cell culture and during acute infection of mice. HSV2-gD27 was attenuated in mice when it was inoculated onto the cornea, intramuscularly (i.m.), intravaginally, and intracranially. Vaccination of mice i.m. with HSV2-gD27 provided better inhibition of challenge virus replication in the vagina than when the virus was used to vaccinate mice intranasally or subcutaneously. Comparison of i.m. vaccinations with HSV2-gD27 versus gD2t in adjuvant showed that HSV2-gD27 induced larger reductions of challenge virus replication in the vagina and reduced latent viral loads in dorsal root ganglia but induced lower serum neutralizing antibody titers than those obtained with gD2t in adjuvant. Taken together, our data indicate that a live attenuated HSV-2 vaccine impaired for infection of neurons provides better protection from vaginal challenge with HSV-2 than that obtained with a subunit vaccine, despite inducing lower titers of HSV-2 neutralizing antibodies in the serum. IMPORTANCE Genital herpes simplex is one of the most prevalent sexually transmitted diseases. Though HSV-2 disease is usually mild, it can be life threatening in neonates and immunocompromised persons. In

  10. Characterisation of genotype VII Newcastle disease virus (NDV) isolated from NDV vaccinated chickens, and the efficacy of LaSota and recombinant genotype VII vaccines against challenge with velogenic NDV.

    Science.gov (United States)

    Roohani, Kiarash; Tan, Sheau Wei; Yeap, Swee Keong; Ideris, Aini; Bejo, Mohd Hair; Omar, Abdul Rahman

    2015-01-01

    A Newcastle disease virus (NDV) isolate designated IBS002 was isolated from a commercial broiler farm in Malaysia. The virus was characterised as a virulent strain based on the multiple basic amino acid motif of the fusion (F) cleavage site (112)RRRKGF(117) and length of the C-terminus extension of the hemagglutinin-neuraminidase (HN) gene. Furthermore, IBS002 was classified as a velogenic NDV with mean death time (MDT) of 51.2 h and intracerebral pathogenicity index (ICPI) of 1.76. A genetic distance analysis based on the full-length F and HN genes showed that both velogenic viruses used in this study, genotype VII NDV isolate IBS002 and genotype VIII NDV isolate AF2240-I, had high genetic variations with genotype II LaSota vaccine. In this study, the protection efficacy of the recombinant genotype VII NDV inactivated vaccine was also evaluated when added to an existing commercial vaccination program against challenge with velogenic NDV IBS002 and NDV AF2240-I in commercial broilers. The results indicated that both LaSota and recombinant genotype VII vaccines offered full protection against challenge with AF2240-I. However, the LaSota vaccine only conferred partial protection against IBS002. In addition, significantly reduced viral shedding was observed in the recombinant genotype VII-vaccinated chickens compared to LaSota-vaccinated chickens.

  11. A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets and monkeys

    Science.gov (United States)

    A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (HA) and neuraminidase (NA) genes of HP A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca) (...

  12. Real-Time PCR Assay To Detect Smallpox Virus

    Science.gov (United States)

    Sofi Ibrahim, M.; Kulesh, David A.; Saleh, Sharron S.; Damon, Inger K.; Esposito, Joseph J.; Schmaljohn, Alan L.; Jahrling, Peter B.

    2003-01-01

    We developed a highly sensitive and specific assay for the rapid detection of smallpox virus DNA on both the Smart Cycler and LightCycler platforms. The assay is based on TaqMan chemistry with the orthopoxvirus hemagglutinin gene used as the target sequence. With genomic DNA purified from variola virus Bangladesh 1975, the limit of detection was estimated to be approximately 25 copies on both machines. The assay was evaluated in a blinded study with 322 coded samples that included genomic DNA from 48 different isolates of variola virus; 25 different strains and isolates of camelpox, cowpox, ectromelia, gerbilpox, herpes, monkeypox, myxoma, rabbitpox, raccoonpox, skunkpox, vaccinia, and varicella-zoster viruses; and two rickettsial species at concentrations mostly ranging from 100 fg/μl to 1 ng/μl. Contained within those 322 samples were variola virus DNA, obtained from purified viral preparations, at concentrations of 1 fg/μl to 1 ng/μl. On the Smart Cycler platform, 2 samples with false-positive results were detected among the 116 samples not containing variola virus tested; i.e., the overall specificity of the assay was 98.3%. On the LightCycler platform, five samples with false-positive results were detected (overall specificity, 95.7%). Of the 206 samples that contained variola virus DNA ranging in concentrations from 100 fg/μl to 1 ng/μl, 8 samples were considered negative on the Smart Cycler platform and 1 sample was considered negative on the LightCycler platform. Thus, the clinical sensitivities were 96.1% for the Smart Cycler instrument and 99.5% for the LightCycler instrument. The vast majority of these samples were derived from virus-infected cell cultures and variola virus-infected tissues; thus, the DNA material contained both viral DNA and cellular DNA. Of the 43 samples that contained purified variola virus DNA ranging in concentration from 1 fg/μl to 1 ng/μl, the assay correctly detected the virus in all 43 samples on both the Smart Cycler

  13. A novel highly reproducible and lethal nonhuman primate model for orthopox virus infection.

    Directory of Open Access Journals (Sweden)

    Marit Kramski

    Full Text Available The intentional re-introduction of Variola virus (VARV, the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV and Monkeypox virus (MPXV cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus.A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1-3 days after onset of symptoms, even when very low infectious viral doses of 5x10(2 pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed.We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50 (minimal monkey infectious dose 50% of 8.3x10(2 pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis.

  14. Monkeypox detection in rodents using real-time 3’minor groove binder Taqman assays on the Roche LightCycler, Laboratory Investigation 84:1200 - 1208

    Science.gov (United States)

    2007-11-02

    DNA 1000 MPV Zaire 79-I-05 10 + + MPXR Zaire 79-I-05 ( Cidofovir - resistant) 10 + + MPV Utrecht 10 + + MPV Sierra Leone 10 + + MPV 12003k 10 + + MPV...100 CMLR— Cidofovir -resistant Camelpox Somalia 100 CPX—cowpox Brighton Red (BR) 100 CPXR— Cidofovir -resistant cowpox Brighton Red 100 VAC...Vaccinia Copenhagen 100 VACR— Cidofovir -resistant Vaccinia Copenhagen 100 HSV-1—Herpes Simplex virus type 1 100 HSV-2—Herpes Simplex virus

  15. Assessment of the cross-protective capability of recombinant capsid proteins derived from pig, rat, and avian hepatitis E viruses (HEV) against challenge with a genotype 3 HEV in pigs.

    Science.gov (United States)

    Sanford, Brenton J; Opriessnig, Tanja; Kenney, Scott P; Dryman, Barbara A; Córdoba, Laura; Meng, Xiang-Jin

    2012-09-28

    Hepatitis E virus (HEV), the causative agent of hepatitis E, is primarily transmitted via the fecal-oral route through contaminated water supplies, although many sporadic cases of hepatitis E are transmitted zoonotically via direct contact with infected animals or consumption of contaminated animal meats. Genotypes 3 and 4 HEV are zoonotic and infect humans and other animal species, whereas genotypes 1 and 2 HEV are restricted to humans. There exists a single serotype of HEV, although the cross-protective ability among the animal HEV strains is unknown. Thus, in this study we expressed and characterized N-terminal truncated ORF2 capsid antigens derived from swine, rat, and avian HEV strains and evaluated their cross-protective ability in a pig challenge model. Thirty, specific-pathogen-free, pigs were divided into 5 groups of 6 pigs each, and each group of pigs were vaccinated with 200 μg of swine HEV, rat HEV, or avian HEV ORF2 antigen or PBS buffer (2 groups) as positive and negative control groups. After a booster dose immunization at 2 weeks post-vaccination, the vaccinated animals all seroconverted to IgG anti-HEV. At 4 weeks post-vaccination, the animals were intravenously challenged with a genotype 3 mammalian HEV, and necropsied at 4 weeks post-challenge. Viremia, fecal virus shedding, and liver histological lesions were compared to assess the protective and cross-protective abilities of these antigens against HEV challenge in pigs. The results indicated that pigs vaccinated with truncated recombinant capsid antigens derived from three animal strains of HEV induced a strong IgG anti-HEV response in vaccinated pigs, but these antigens confer only partial cross-protection against a genotype 3 mammalian HEV. The results have important implications for the efficacy of current vaccines and for future vaccine development, especially against the novel zoonotic animal strains of HEV.

  16. Lemna (duckweed) expressed hemagglutinin from avian influenza H5N1 protects chickens against H5N1 high pathogenicity avian influenza virus challenge

    Science.gov (United States)

    In the last two decades, transgenic plants have been explored as safe and cost effective alternative expression platforms for producing recombinant proteins. In this study, a synthetic hemagglutinin (HA) gene from the high pathogenicity avian influenza (HPAI) virus A/chicken/Indonesia/7/2003 (H5N1)...

  17. Challenges for bovine viral diarrhoea virus antibody detection in bulk milk by antibody enzyme-linked immunosorbent assays due to changes in milk production levels

    DEFF Research Database (Denmark)

    Foddai, Alessandro; Enøe, Claes; Stockmarr, Anders

    2015-01-01

    Background: Bovine viral diarrhoea (BVD) is considered eradicated from Denmark. Currently, very few (if any) Danish cattle herds could be infected with BVD virus (BVDV). The Danish antibody blocking enzyme-linked immunosorbent assay (ELISA) has been successfully used during the Danish BVD eradica...

  18. Experimental evaluation of killed and live Newcastle disease virus vaccines heterologous to the virulent genotype XII challenge strain from the Peru/2008 outbreak

    Science.gov (United States)

    While all Newcastle disease viruses (NDV) are contained within one serotype and different NDV provide cross-protection against others, antigenically matched strains have been shown to decrease viral shedding. Therefore, using recombinant technology, some companies have directed efforts in developin...

  19. A virosomal respiratory syncytial virus vaccine adjuvanted with monophosphoryl lipid A provides protection against viral challenge without priming for enhanced disease in cotton rats

    NARCIS (Netherlands)

    Kamphuis, Tobias; Stegmann, Toon; Meijerhof, Tjarko; Wilschut, Jan; de Haan, Aalzen

    2013-01-01

    Background Non-replicating respiratory syncytial virus (RSV) vaccine candidates could potentially prime for enhanced respiratory disease (ERD) due to a T-cell-mediated immunopathology, following RSV infection. Vaccines with built-in immune response modifiers, such as Toll-like receptor (TLR)

  20. Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using direct homologous challenge

    Science.gov (United States)

    The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularl...

  1. Challenging Students' Intuitions--The Influence of a Tangible Model of Virus Assembly on Students' Conceptual Reasoning about the Process of Self-Assembly

    Science.gov (United States)

    Larsson, Caroline; Tibell, Lena A.

    2015-01-01

    A well-ordered biological complex can be formed by the random motion of its components, i.e. self-assemble. This is a concept that incorporates issues that may contradict students' everyday experiences and intuitions. In previous studies, we have shown that a tangible model of virus self-assembly, used in a group exercise, helps students to grasp…

  2. MicroRNA expression profiling in tonsils of calves challenged with a laboratory strain or field isolates of Bovine Respiratory Syncytial Virus

    Science.gov (United States)

    Bovine respiratory syncytial virus (BRSV) is a leading cause of bovine respiratory disease in cattle worldwide. MicroRNAs have been suggested to play a role in viral infections via their regulation of cellular molecules involved in either viral replication or in host innate immunity to infection. Th...

  3. Immunogenicity of avian influenza H7N9 virus in birds: Identification of viral epitopes recognized by the immune system following vaccination and challenge

    Science.gov (United States)

    In March of 2013, the first cases of H7N9 influenza were reported in humans in China and shortly thereafter the virus was isolated from poultry in live bird markets. In 2014, a second wave of human infections occurred with similar mortality rates. The genetic composition of these H7N9 influenza vi...

  4. Efficacy of a modified live intranasal bovine respiratory syncytial virus vaccine in three-week-old calves experimentally challenged with BRSV

    NARCIS (Netherlands)

    Vangeel, I.; Antonis, A.F.G.; Fluess, M.; Peters, A.R.; Harmeyer, S.S.

    2005-01-01

    Bovine respiratory syncytial virus (BRSV) is a widespread cause of lower respiratory tract disease in cattle. Calves less than four months of age are often involved in outbreaks of respiratory disease. We evaluated the efficacy of a single intranasal dose of a bivalent modified live vaccine containi

  5. Determination of efficacious vaccine seed strains for use against Egyptian H5N1 highly pathogenic avian influenza viruses through antigenic cartography and in vivo challenge studies

    Science.gov (United States)

    Since 2006, there have been reported outbreaks of H5N1 highly pathogenic avian influenza (HPAI) in vaccinated chickens in Africa and Asia. This study provides experimental data for selection of efficacious H5N1 vaccine seed strains against recently circulating strains of H5N1 HPAI viruses in Egypt....

  6. African Swine Fever Virus Georgia isolate harboring deletions of 9GL and MGF360/505 genes in highly attenuated in swine but does not confer protection against parental virus challenge

    Science.gov (United States)

    African swine fever virus (ASFV) produces a contagious disease of domestic pigs that results in severe economic consequences to the swine industry. Control of the disease has been hampered by the unavailability of vaccines. We recently reported the development of two experimental vaccine strains (...

  7. Deletion of African swine fever virus Georgia 2007 virulence-associated gene 9GL (B119L) leads to virus attenuation in swine at low doses while inducing an effective protection against homologous challenge

    Science.gov (United States)

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs that has significant economic consequences for swine breeding. The control of African Swine Fever (ASF) has been hampered by the unavailability of vaccines. Experimental vaccines...

  8. African swine fever virus Georgia isolate harboring deletions of MGF360 and MGF505 genes is attenuated in swine and confers protection against challenge with the virulent parental virus

    Science.gov (United States)

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. The control of African Swine Fever (ASF) has been hampered by the unavailability of vaccines. Experimental vaccines h...

  9. Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV

    Science.gov (United States)

    Liu, Ye V.; Massare, Michael J.; Barnard, Dale L.; Kort, Thomas; Nathan, Margret; Wang, Lei; Smith, Gale

    2011-01-01

    SARS-CoV was the cause of the global pandemic in 2003 that infected over 8000 people in 8 months. Vaccines against SARS are still not available. We developed a novel method to produce high levels of a recombinant SARS virus-like particles (VLPs) vaccine containing the SARS spike (S) protein and the influenza M1 protein using the baculovirus insect cell expression system. These chimeric SARS VLPs have a similar size and morphology to the wild type SARS-CoV. We tested the immunogenicity and protective efficacy of purified chimeric SARS VLPs and full length SARS S protein vaccines in a mouse lethal challenge model. The SARS VLP vaccine, containing 0.8 μg of SARS S protein, completely protected mice from death when administered intramuscular (IM) or intranasal (IN) routes in the absence of an adjuvant. Likewise, the SARS VLP vaccine, containing 4 μg of S protein without adjuvant, reduced lung virus titer to below detectable level, protected mice from weight loss, and elicited a high level of neutralizing antibodies against SARS-CoV. Sf9 cell-produced full length purified SARS S protein was also an effective vaccine against SARS-CoV but only when co-administered IM with aluminum hydroxide. SARS-CoV VLPs are highly immunogenic and induce neutralizing antibodies and provide protection against lethal challenge. Sf9 cell-based VLP vaccines are a potential tool to provide protection against novel pandemic agents. PMID:21762752

  10. A Multi-Agent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges

    Science.gov (United States)

    2016-07-26

    and 44 eastern equine encephalitis virus (EEEV) are recognized as significant biological defense threats . 45 There are currently no licensed human...stable (4). 75 Consequently, VEEV, WEEV, and EEEV represent significant potential biological defense 76 threats and are classified as Category B...obtained from vaccinated mice using 223 BD Falcon 100 µM nylon cell strainers ( Corning , Catalog # 352360) were resuspended in 224 complete RPMI 1640

  11. EPIPOX: Immunoinformatic Characterization of the Shared T-Cell Epitome between Variola Virus and Related Pathogenic Orthopoxviruses.

    Science.gov (United States)

    Molero-Abraham, Magdalena; Glutting, John-Paul; Flower, Darren R; Lafuente, Esther M; Reche, Pedro A

    2015-01-01

    Concerns that variola viruses might be used as bioweapons have renewed the interest in developing new and safer smallpox vaccines. Variola virus genomes are now widely available, allowing computational characterization of the entire T-cell epitome and the use of such information to develop safe and yet effective vaccines. To this end, we identified 124 proteins shared between various species of pathogenic orthopoxviruses including variola minor and major, monkeypox, cowpox, and vaccinia viruses, and we targeted them for T-cell epitope prediction. We recognized 8,106, and 8,483 unique class I and class II MHC-restricted T-cell epitopes that are shared by all mentioned orthopoxviruses. Subsequently, we developed an immunological resource, EPIPOX, upon the predicted T-cell epitome. EPIPOX is freely available online and it has been designed to facilitate reverse vaccinology. Thus, EPIPOX includes key epitope-focused protein annotations: time point expression, presence of leader and transmembrane signals, and known location on outer membrane structures of the infective viruses. These features can be used to select specific T-cell epitopes suitable for experimental validation restricted by single MHC alleles, as combinations thereof, or by MHC supertypes.

  12. Concurrent vaccination of pigs with type 1 and type 2 porcine reproductive and respiratory syndrome virus (PRRSV) protects against type 1 PRRSV but not against type 2 PRRSV on dually challenged pigs.

    Science.gov (United States)

    Park, Changhoon; Choi, Kyuhyung; Jeong, Jiwoon; Kang, Ikjae-; Park, Su-Jin; Chae, Chanhee

    2015-12-01

    The objective of the present study was to evaluate the effect of concurrent vaccination of pigs with both type 1 and type 2 porcine reproductive and respiratory syndrome virus (PRRSV) vaccine against heterologous dual challenge of both genotypes and compare with single vaccination of pigs against heterologous single challenge of both genotypes. Pigs were administered both type 1 and type 2 PRRSV vaccine concurrently into separate anatomical sites at 28 days of age and inoculated intranasally with both genotypes at 63 days of age. Neutralizing antibodies (NA) were not detected in any pigs in any group (NA titer vaccination of pigs with two PRRSV genotypes had significantly lower numbers of type 1 and type 2 PRRSV-specific interferon-γ secreting cells (IFN-γ-SC) compared to vaccination of pigs with type 1 or type 2 PRRSV only. Despite the decreased induction of type 1 PRRSV-specific IFN-γ-SC, concurrent vaccination is still able to reduce type 1 PRRSV viremia whereas the decreased induction of type 2 PRRSV-specific IFN-γ-SC by concurrent vaccination correlates with lack of reduction of type 2 PRRSV viremia after dual challenge. The results of this study demonstrated that concurrent vaccination of pigs with two PRRSV genotypes is able to reduce the levels of type 1 PRRSV viremia and lung lesions but not able to reduce the levels of type 2 PRRSV viremia and lung lesions.

  13. The combination of attenuated Newcastle disease (ND) vaccine with rHVT-ND vaccine at 1 day old is more protective against ND virus challenge than when combined with inactivated ND vaccine.

    Science.gov (United States)

    Rauw, F; Gardin, Y; Palya, V; van den Berg, T; Lambrecht, B

    2014-01-01

    The recurrent outbreaks of fatal Newcastle disease (ND) in commercial poultry flocks throughout the world indicate that routine vaccinations are failing to sufficiently induce the high levels of immunity necessary to control ND. There is a need for vaccination programmes that could be initiated at 1-day-old for mass application and which would induce a long-lasting immunity, with no need for a booster vaccination at a later age. In this context, the duration of immunity delivered by a vaccination programme including a recombinant herpesvirus of turkeys expressing the F gene of ND virus (rHVT-ND) and live ND vaccine at 1-day-old was compared with a classical programme that included a conventional live and an inactivated ND vaccine at the same age in commercial layer chickens. The humoral, cell-mediated and local immunity were followed weekly and birds were challenged with a viscerotropic velogenic ND virus strain at 6 and 10 weeks of age. We determined that immunity induced by the vaccination programme involving the rHVT-ND vaccine was more protective than that provided by the conventional vaccine-based regime. This might be related to a T-helper type 1 (Th1) cellular-driven immunological response, in contrast to the T-helper type 2 (Th2) humoral-oriented immune response provided by the current conventional vaccine-based vaccination programmes.

  14. Informing the Historical Record of Experimental Nonhuman Primate Infections with Ebola Virus: Genomic Characterization of USAMRIID Ebola Virus/H.sapiens-tc/COD/1995/Kikwit-9510621 Challenge Stock “R4368” and Its Replacement “R4415”

    Science.gov (United States)

    Kugelman, Jeffrey R.; Rossi, Cynthia A.; Wiley, Michael R.; Ladner, Jason T.; Nagle, Elyse R.; Pfeffer, Bradley P.; Garcia, Karla; Prieto, Karla; Wada, Jiro; Kuhn, Jens H.; Palacios, Gustavo

    2016-01-01

    The creation of licensed medical countermeasures against Select Agents such as Ebola virus (EBOV) is critically dependent on the use of standardized reagents, assays, and animal models. We performed full genome reconstruction, population genomics, contaminant analysis, and characterization of the glycoprotein gene editing site of historical United States Army Medical Research Institute of Infectious Diseases (USAMRIID) nonhuman-primate challenge stock Ebola virus Kikwit “R4368” and its 2014 replacement “R4415.” We also provide characterization of the master stock used to create “R4415.” The obtained data are essential to understanding the quality of the seed stock reagents used in pivotal animal studies that have been used to inform medical countermeasure development. Furthermore, these data might add to the understanding of the influence of EBOV variant populations on pathogenesis and disease outcome and inform attempts to avoid the evolution of EBOV escape mutants in response to current therapeutics. Finally, as the primary challenge stocks have changed over time, these data will provide a baseline for understanding and correlating past and future animal study results. PMID:27002733

  15. Radiology preparedness in ebola virus disease: guidelines and challenges for disinfection of medical imaging equipment for the protection of staff and patients.

    Science.gov (United States)

    Mollura, Daniel J; Palmore, Tara N; Folio, Les R; Bluemke, David A

    2015-05-01

    The overlap of early Ebola virus disease (EVD) symptoms (eg, fever, headache, abdominal pain, diarrhea, emesis, and fatigue) with symptoms of other more common travel-related diseases (eg, malaria, typhoid fever, pneumonia, and meningococcemia) may result in delayed diagnosis of EVD before isolation of infected patients. Radiology departments should consider policies for and approaches to decontamination of expensive and potentially easily damaged radiology equipment. In addition, the protection of radiology personnel must be considered during the work-up phase of undiagnosed EVD patients presenting to emergency departments. The purpose of this article is to consider the effect of EVD on radiology departments and imaging equipment, with particular consideration of guidelines currently available from the Centers for Disease Control and Prevention that may be applicable to radiology. (©) RSNA, 2015.

  16. Viruses as teratogens.

    Science.gov (United States)

    Oberst, R D

    1993-03-01

    The ability of certain viruses to affect prenatal development in domestic animals is well documented. However, differentiating a viral-induced malformation from those caused by genetic or other environmental causes is a diagnostic dilemma. Understanding how viruses interact with their embryo-fetal hosts and the potential consequences on prenatal development requires refining and dispelling some old concepts and injecting new insights into this diagnostic challenge. This article discusses several viral teratogens affecting domestic animals: Akabane, bluetongue, Cache Valley, Japanese B encephalitis, bovine viral diarrhea, Border disease, Chuzan, epizootic hemorrhagic disease, hog cholera, Rift Valley fever, and Wesselsbron disease viruses.

  17. Responses of three very large inducible GTPases to bacterial and white spot syndrome virus challenges in the giant fresh water prawn Macrobrachium rosenbergii.

    Science.gov (United States)

    Huang, Ying; Jin, Min; Yin, Shaowu; Ding, Zhengfeng; Wang, Wen; Ren, Qian

    2016-04-01

    Interferons (IFNs) are cytokines secreted by cells in response to invasion by pathogens, such as viruses, bacteria, parasites, or tumor cells. Very large inducible GTPases (VLIG) are the latest IFN-inducible GTPase family to be discovered and are the largest known GTPases of any species. However, VLIG proteins from invertebrates have yet to be characterized. In this study, three forms of VLIGs designated as MrVLIG1, MrVLIG2, and MrVLIG3 were cloned from the giant fresh water prawn Macrobrachium rosenbergii. MrVLIG1 has a 5445 bp open reading frame (ORF) encoding an 1814-amino acid protein. The complete nucleotide sequence of MrVLIG2 cDNA is 7055 bp long consisting of a 5757 bp ORF encoding a protein with 1918 amino acids. The full length of the MrVLIG3 gene consists of 5511 bp with a 3909 bp ORF encoding a peptide with 1302 amino acids. BLASTP and phylogenetic tree analyses showed that the three MrVLIGs are clustered into one subgroup and, together with other vertebrate VLIGs, into a branch. Tissue distribution analysis indicated that the mRNAs of the three MrVLIGs were widely expressed in almost all detected tissues, including the hemocytes, heart, hepatopancreas, gills, stomach, and intestine, with the highest expression in the hepatopancreas. They were also detected in the intestine but with relatively low expression levels. Quantitative real-time RT-PCR analysis showed that the mRNA transcripts of the MrVLIGs in the hepatopancreas were significantly expressed at various time points after infection with Vibrio parahaemolyticus and white spot syndrome virus. In summary, the three isoforms of VLIG genes participate in the innate immune response of the shrimps to bacterial and viral infections.

  18. Use of Vaccinia Virus Smallpox Vaccine in Laboratory and Health Care Personnel at Risk for Occupational Exposure to Orthopoxviruses - Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2015.

    Science.gov (United States)

    Petersen, Brett W; Harms, Tiara J; Reynolds, Mary G; Harrison, Lee H

    2016-03-18

    On June 25, 2015, the Advisory Committee on Immunization Practices (ACIP) recommended routine vaccination with live smallpox (vaccinia) vaccine (ACAM2000) for laboratory personnel who directly handle 1) cultures or 2) animals contaminated or infected with replication-competent vaccinia virus, recombinant vaccinia viruses derived from replication-competent vaccinia strains (i.e., those that are capable of causing clinical infection and producing infectious virus in humans), or other orthopoxviruses that infect humans (e.g., monkeypox, cowpox, and variola) (recommendation category: A, evidence type 2 [Box]). Health care personnel (e.g., physicians and nurses) who currently treat or anticipate treating patients with vaccinia virus infections and whose contact with replication-competent vaccinia viruses is limited to contaminated materials (e.g., dressings) and persons administering ACAM2000 smallpox vaccine who adhere to appropriate infection prevention measures can be offered vaccination with ACAM2000 (recommendation category: B, evidence type 2 [Box]). These revised recommendations update the previous ACIP recommendations for nonemergency use of vaccinia virus smallpox vaccine for laboratory and health care personnel at risk for occupational exposure to orthopoxviruses (1). Since 2001, when the previous ACIP recommendations were developed, ACAM2000 has replaced Dryvax as the only smallpox vaccine licensed by the U.S. Food and Drug Administration (FDA) and available for use in the United States (2). These recommendations contain information on ACAM2000 and its use in laboratory and health care personnel at risk for occupational exposure to orthopoxviruses.

  19. Viruses in reptiles.

    Science.gov (United States)

    Ariel, Ellen

    2011-09-21

    The etiology of reptilian viral diseases can be attributed to a wide range of viruses occurring across different genera and families. Thirty to forty years ago, studies of viruses in reptiles focused mainly on the zoonotic potential of arboviruses in reptiles and much effort went into surveys and challenge trials of a range of reptiles with eastern and western equine encephalitis as well as Japanese encephalitis viruses. In the past decade, outbreaks of infection with West Nile virus in human populations and in farmed alligators in the USA has seen the research emphasis placed on the issue of reptiles, particularly crocodiles and alligators, being susceptible to, and reservoirs for, this serious zoonotic disease. Although there are many recognised reptilian viruses, the evidence for those being primary pathogens is relatively limited. Transmission studies establishing pathogenicity and cofactors are likewise scarce, possibly due to the relatively low commercial importance of reptiles, difficulties with the availability of animals and permits for statistically sound experiments, difficulties with housing of reptiles in an experimental setting or the inability to propagate some viruses in cell culture to sufficient titres for transmission studies. Viruses as causes of direct loss of threatened species, such as the chelonid fibropapilloma associated herpesvirus and ranaviruses in farmed and wild tortoises and turtles, have re-focused attention back to the characterisation of the viruses as well as diagnosis and pathogenesis in the host itself.

  20. ECHO virus

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001340.htm ECHO virus To use the sharing features on this page, please enable JavaScript. Enteric cytopathic human orphan (ECHO) viruses are a group of viruses that lead to ...

  1. EPIPOX: Immunoinformatic Characterization of the Shared T-Cell Epitome between Variola Virus and Related Pathogenic Orthopoxviruses

    Directory of Open Access Journals (Sweden)

    Magdalena Molero-Abraham

    2015-01-01

    developing new and safer smallpox vaccines. Variola virus genomes are now widely available, allowing computational characterization of the entire T-cell epitome and the use of such information to develop safe and yet effective vaccines. To this end, we identified 124 proteins shared between various species of pathogenic orthopoxviruses including variola minor and major, monkeypox, cowpox, and vaccinia viruses, and we targeted them for T-cell epitope prediction. We recognized 8,106, and 8,483 unique class I and class II MHC-restricted T-cell epitopes that are shared by all mentioned orthopoxviruses. Subsequently, we developed an immunological resource, EPIPOX, upon the predicted T-cell epitome. EPIPOX is freely available online and it has been designed to facilitate reverse vaccinology. Thus, EPIPOX includes key epitope-focused protein annotations: time point expression, presence of leader and transmembrane signals, and known location on outer membrane structures of the infective viruses. These features can be used to select specific T-cell epitopes suitable for experimental validation restricted by single MHC alleles, as combinations thereof, or by MHC supertypes.

  2. Zika virus: a new challenge to arboviral diseases%Zika病毒:虫媒病毒传染病的新挑战

    Institute of Scientific and Technical Information of China (English)

    李晓龙; 严延生; 王环宇; 梁国栋

    2016-01-01

    Zika病毒(Zika virus,ZIKV)是一种新发的虫媒病毒,伊蚊是其主要的传播媒介.Zika病毒感染后主要引起发热,皮疹,关节痛等轻症症状.2015年起,Zika病毒在拉丁美洲及南美洲多个国家流行,并且Zika病毒感染患者不仅出现发热,皮疹和关节痛等症状,还发现Zika病毒病的流行与婴儿小头畸形,格林巴利综合征,病毒性脑膜炎病例的发生相关.不仅如此,Zika病毒感染还可以通过性途径传播.因此,从病毒感染症状的复杂性来看,目前流行的Zika病毒已经与1947年刚发现时的Zika病毒完全不同,而是成为了一种“新病毒”.本文系统地梳理总结了Zika病毒感染相关的最新研究进展,并提出Zika病毒及其感染是对虫媒病毒传染病的新挑战的概念.

  3. Challenging Students' Intuitions—the Influence of a Tangible Model of Virus Assembly on Students' Conceptual Reasoning About the Process of Self-Assembly

    Science.gov (United States)

    Larsson, Caroline; Tibell, Lena A. E.

    2015-10-01

    A well-ordered biological complex can be formed by the random motion of its components, i.e. self-assemble. This is a concept that incorporates issues that may contradict students' everyday experiences and intuitions. In previous studies, we have shown that a tangible model of virus self-assembly, used in a group exercise, helps students to grasp the process of self-assembly and in particular the facet "random molecular collision". The present study investigates how and why the model and the group exercise facilitate students' learning of this particular facet. The data analysed consist of audio recordings of six group exercises ( n = 35 university students) and individual semi-structured interviews ( n = 5 university students). The analysis is based on constructivist perspectives of learning, a combination of conceptual change theory and learning with external representations. Qualitative analysis indicates that perceived counterintuitive aspects of the process created a cognitive conflict within learners. The tangible model used in the group exercises facilitated a conceptual change in their understanding of the process. In particular, the tangible model appeared to provide cues and possible explanations and functioned as an "eye-opener" and a "thinking tool". Lastly, the results show signs of emotions also being important elements for successful accommodation.

  4. Performance and immunological resistance of Litopenaeus vannamei fed a β-1,3/1,6-glucan-supplemented diet after per os challenge with the Infectious myonecrosis virus (IMNV

    Directory of Open Access Journals (Sweden)

    Hassan Sabry Neto

    2015-05-01

    Full Text Available This study determined the efficacy of a β-1,3/1,6-glucan source on the survival, growth, and immunological responses of Litopenaeus vannamei challenged with infectious myonecrosis virus (IMNV. The work was conducted in 20 tanks of 500 L with clear water with constant recirculation and aeration. Shrimp weighing 2.6±0.4 g were stocked at 100 animals/m2 and reared for 10 weeks. Viral challenge occurred through oral administration of IMNV positive extract (1.82 £ × 103 copies of IMNV/µL RNA during three consecutive days, twice a day. One treatment and three controls, with five replicatetanks each, were used, as follows: Com - commercial diet fed to non-challenged shrimp (NCS; Ref - lab-manufactured basal diet, deprived of β-1,3/1,6- glucan fed to NCS; IMNV-Ref - basal diet fed to IMNV-challenged shrimp; and, IMNV-BetG - basal diet with 1,000 mg/kg of a β-1,3/1,6-glucan. Per os challenge began on the 29th day of rearing (4.93-g to 6.92-g shrimp. Shrimp were effectively contaminated with IMNV. Animals were highly susceptible to IMNV four weeks after the first day of infection when mortality peaked. Shrimp in the Com treatment (69.5±12.7% reached the highest survival, but it did not differ from the Ref group (57.9±9.21%. Shrimp under the IMNV-Ref treatment achieved the lowest survival (23.2±5.76%. Survival for IMNV-BetG (48.1±8.53% was significantly higher than IMNV-Ref, and similar to the Ref group. Total hemocyte count was significantly affected by treatment and hemolymph sampling time, while serum protein concentration and phenoloxidase activity did not change. Addition of 1,000 mg/kg of β-1,3/1,6-glucan in a diet for L. vannamei enhances shrimp survival when orally exposed to IMNV. No signs of immunological fatigue or detriment in growth are detected when the species is continually exposed to this diet.

  5. Comparison Research of Infectious Bovine Rhinotracheitis Virus Challenge%牛传染性鼻气管炎病毒攻毒方式的对比研究

    Institute of Scientific and Technical Information of China (English)

    郭利; 张淑琴; 冷雪; 王炜; 武华

    2012-01-01

    This study is to determine the most effective inoculation mode and the distribution of infectious bovine rhinotracheitis virus (IBRV) in experimental animals, which is used to evaluate the protective efficiency of attenuated vaccine strain LNM. 9 cows post-ablactation were divided into test groups (nasal sprays group, nasal drops group) and control group, each group contains 3 cows. Test groups were inoculated with virulent strain of LN01/08 by nasal sprays and nasal drops, respectively, and the data of daily clinical symptoms, body temperature and nasal swab were collected for consecutive 14 days post-inoculation. Experimental animals in different clinical period post-onset were killed and main internal organs were collected for virus isolation. The test results showed that all animals post-inoculation developed different extent clinical signs (the nasal spray group animals performed more seriously), and IBRV were most distributed at tissues of respiratory and ocular conjunctiva. It is concluded that experimental animals inoculated with IBRV by nasal sprays was better than that by nasal drops, which could provide a basis for develop IBR vaccine and evaluate immune effect of IBRV vaccine.%本试验旨在建立牛传染性鼻气管炎病毒的攻毒模型,明确病毒在牛体内的分布及确定最佳攻毒方式,建立牛传染性鼻气管炎的发病标准,用来评价IBRV LNM弱毒疫苗的保护效力.试验共使用健康断乳牛9头,设鼻内喷雾组、滴鼻组和对照共3组,每组3头牛.将实验室分离保存的IBRV LN01/08强毒株采用鼻内喷雾和滴鼻两种方式接种试验组动物后,连续14 d,每日观察临床症状,监测体温及采集鼻拭子,对收集的试验数据进行对比分析.选取临床发病不同时期剖杀动物,采取主要脏器进行病毒分离.结果显示,所有动物攻毒后有不同程度的临床表现,以鼻内喷雾组临床表现最为严重,剖检可见肺部病变明显.病毒主要分布在呼吸道

  6. Comparative analysis of the acute response of the trout, O. mykiss, head kidney to in vivo challenge with virulent and attenuated infectious hematopoietic necrosis virus and LPS-induced inflammation

    Directory of Open Access Journals (Sweden)

    Roher Nerea

    2008-03-01

    Full Text Available Abstract Background The response of the trout, O. mykiss, head kidney to bacterial lipopolysaccharide (LPS or active and attenuated infectious hematopoietic necrosis virus (IHNV and attINHV respectively intraperitoneal challenge, 24 and 72 hours post-injection, was investigated using a salmonid-specific cDNA microarray. Results The head kidney response to i.p. LPS-induced inflammation in the first instance displays an initial stress reaction involving suppression of major cellular processes, including immune function, followed by a proliferative hematopoietic-type/biogenesis response 3 days after administration. The viral response at the early stage of infection highlights a suppression of hematopoietic and protein biosynthetic function and a stimulation of immune response. In fish infected with IHNV a loss of cellular function including signal transduction, cell cycle and transcriptional activity 72 hours after infection reflects the tissue-specific pathology of IHNV infection. attIHNV treatment on the other hand shows a similar pattern to native IHNV infection at 24 hours however at 72 hours a divergence from the viral response is seen and replace with a recovery response more similar to that observed for LPS is observed. Conclusion In conclusion we have been able to identify and characterise by transcriptomic analysis two different types of responses to two distinct immune agents, a virus, IHNV and a bacterial cell wall component, LPS and a 'mixed' response to an attenuated IHNV. This type of analysis will lead to a greater understanding of the physiological response and the development of effective immune responses in salmonid fish to different pathogenic and pro-inflammatory agents.

  7. Challenges of Biobanking in South Africa to Facilitate Indigenous Research in an Environment Burdened with Human Immunodeficiency Virus, Tuberculosis, and Emerging Noncommunicable Diseases

    Science.gov (United States)

    Christoffels, Alan; Grewal, Ravnit; Karam, Locunda A.; Rossouw, Catherine; Staunton, Ciara; Swanepoel, Carmen; van Rooyen, Beverley

    2013-01-01

    The high burden of infectious diseases and the growing problem of noncommunicable and metabolic disease syndromes in South Africa (SA) forces a more focused research approach to facilitate cutting-edge scientific growth and public health development. Increased SA research on these diseases and syndromes and the collection of associated biospecimens has ensured a plethora of biobanks created by individuals, albeit without the foresight of prospective and collective use by other local and international researchers. As the need for access to high-quality specimens in statistically relevant numbers has increased, so has the necessity for the development of national human biobanks in SA and across the Continent. The prospects of achieving sustainable centralized biobanks are still an emerging and evolving concept, primarily and recently driven by the launch of the H3Africa consortium, which includes the development of harmonized and standardized biobanking operating procedures. This process is hindered by a myriad of complex societal considerations and ethico-legal challenges. Efforts to consolidate and standardize biological sample collections are further compromised by the lack of full appreciation by national stakeholders of the biological value inherent in these collections, and the availability of high quality human samples with well-annotated data for future scientific research and development. Inadequate or nonexistent legislative structures that specifically regulate the storage, use, dispersal, and disposal of human biological samples are common phenomena and pose further challenges. Furthermore, concerns relating to consent for unspecified future uses, as well as access to information and data protection, are all new paradigms that require further consideration and public engagement. This article reviews important fundamental issues such as governance, ethics, infrastructure, and bioinformatics that are important foundational prerequisites for the

  8. Pharmacodynamics of cidofovir for vaccinia virus infection in an in vitro hollow-fiber infection model system.

    Science.gov (United States)

    McSharry, James J; Deziel, Mark R; Zager, Kris; Weng, Qingmei; Drusano, George L

    2009-01-01

    Variola major virus remains a potent weapon of bioterror. There is currently an investigational-new-drug application for cidofovir for the therapy of variola major virus infections. Stittelaar and colleagues compared the levels of effectiveness of postexposure smallpox vaccination (Elstree-RIVM) and antiviral treatment with cidofovir or an acyclic nucleoside phosphonate analogue 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidine (HPMPO-DAPy) after lethal intratracheal infection of cynomolgus monkeys with monkeypox virus, a variola virus surrogate. Their results demonstrated that either compound was more effective than vaccination with the Ellstree vaccine (K. J. Stittelaar et al., Nature 439:745-748, 2006). An unanswered question is how to translate this information into therapy for poxvirus infections in people. In a proof-of-principle study, we used a novel in vitro hollow-fiber infection model system to determine the pharmacodynamics of vaccinia virus infection of HeLa-S3 cells treated with cidofovir. Our results demonstrate that the currently licensed dose of cidofovir of 5 mg/kg of body weight weekly with probenecid (which ameliorates nephrotoxicity) is unlikely to provide protection for patients intentionally exposed to Variola major virus. We further demonstrate that the antiviral effect is independent of the schedule of drug administration. Exposures (area under the concentration-time curve) to cidofovir that will have a robust protective effect will require doses that are 5 to 10 times that currently administered to humans. Such doses may cause nephrotoxicity, and therefore, approaches that include probenecid administration as well as schedules of administration that will help ameliorate the uptake of cidofovir into renal tubular epithelial cells need to be considered when addressing such treatment for people.

  9. Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein.

    Science.gov (United States)

    Bertagnoli, S; Gelfi, J; Le Gall, G; Boilletot, E; Vautherot, J F; Rasschaert, D; Laurent, S; Petit, F; Boucraut-Baralon, C; Milon, A

    1996-08-01

    Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma virus-specific antibodies in rabbits after immunization. Inoculations by the intradermal route protected animals against virulent RHDV and myxoma virus challenges.

  10. Genomic exploration of individual giant ocean viruses.

    Science.gov (United States)

    Wilson, William H; Gilg, Ilana C; Moniruzzaman, Mohammad; Field, Erin K; Koren, Sergey; LeCleir, Gary R; Martínez Martínez, Joaquín; Poulton, Nicole J; Swan, Brandon K; Stepanauskas, Ramunas; Wilhelm, Steven W

    2017-08-01

    Viruses are major pathogens in all biological systems. Virus propagation and downstream analysis remains a challenge, particularly in the ocean where the majority of their microbial hosts remain recalcitrant to current culturing techniques. We used a cultivation-independent approach to isolate and sequence individual viruses. The protocol uses high-speed fluorescence-activated virus sorting flow cytometry, multiple displacement amplification (MDA), and downstream genomic sequencing. We focused on 'giant viruses' that are readily distinguishable by flow cytometry. From a single-milliliter sample of seawater collected from off the dock at Boothbay Harbor, ME, USA, we sorted almost 700 single virus particles, and subsequently focused on a detailed genome analysis of 12. A wide diversity of viruses was identified that included Iridoviridae, extended Mimiviridae and even a taxonomically novel (unresolved) giant virus. We discovered a viral metacaspase homolog in one of our sorted virus particles and discussed its implications in rewiring host metabolism to enhance infection. In addition, we demonstrated that viral metacaspases are widespread in the ocean. We also discovered a virus that contains both a reverse transcriptase and a transposase; although highly speculative, we suggest such a genetic complement would potentially allow this virus to exploit a latency propagation mechanism. Application of single virus genomics provides a powerful opportunity to circumvent cultivation of viruses, moving directly to genomic investigation of naturally occurring viruses, with the assurance that the sequence data is virus-specific, non-chimeric and contains no cellular contamination.

  11. Effects of acute change in salinity and moulting on the infection of white leg shrimp (Penaeus vannamei) with white spot syndrome virus upon immersion challenge.

    Science.gov (United States)

    Van Thuong, K; Van Tuan, V; Li, W; Sorgeloos, P; Bossier, P; Nauwynck, H

    2016-12-01

    In the field, moulting and salinity drop in the water due to excessive rainfall have been mentioned to be risk factors for WSSV outbreaks. Therefore, in this study, the effect of an acute change in environmental salinity and shedding of the old cuticle shell on the susceptibility of Penaeus vannamei to WSSV was evaluated by immersion challenge. For testing the effect of abrupt salinity stress, early premoult shrimp that were acclimated to 35 g L(-1) were subjected to salinities of 50 g L(-1) , 35 g L(-1) , 20 g L(-1) , 10 g L(-1) and 7 g L(-1) or 5 g L(-1) and simultaneously exposed to 10(5.5)  SID50 mL(-1) of WSSV for 5 h, after which the salinity was brought back to 35 g L(-1) . Shrimp that were transferred from 35 g L(-1) to 50 g L(-1) , 35 g L(-1) and 20 g L(-1) did not become infected with WSSV. Shrimp became infected with WSSV after an acute salinity drop from 35 g L(-1) to 10 g L(-1) and lower. The mortality in shrimp, subjected to a salinity change to 10 g L(-1) , 7 g L(-1) and 5 g L(-1) , was 6.7%, 46.7% and 53.3%, respectively (P shrimp in early premoult, moulting and post-moult were immersed in sea water containing 10(5.5)  SID50 mL(-1) of WSSV. The resulting mortality due to WSSV infection in shrimp inoculated during early premoult (0%), ecdysis (53.3%) and post-moult (26.72%) demonstrated that a significant difference exists in susceptibility of shrimp during the short moulting process (P shrimp are at risk for a WSSV infection. These findings have important implications for WSSV control measures. © 2016 John Wiley & Sons Ltd.

  12. Human Influenza Virus Infections.

    Science.gov (United States)

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection.

  13. Zika virus: Indian perspectives

    Directory of Open Access Journals (Sweden)

    Devendra T Mourya

    2016-01-01

    Full Text Available The emergence of Zika virus (ZiV, a mosquito borne Flavivirus like dengue (DEN and chikungunya (CHIK, in Brazil in 2014 and its spread to various countries have led to a global health emergency. Aedes aegypti is the major vector for ZiV. Fast dissemination of this virus in different geographical areas posses a major threat especially to regions where the population lacks herd immunity against the ZiV and there is abundance of Aedes mosquitoes. In this review, we focus on current global scenario, epidemiology, biology, diagnostic challenges and remedial measures for ZiVconsidering the Indian perspective.

  14. Zika virus: Indian perspectives.

    Science.gov (United States)

    Mourya, Devendra T; Shil, Pratip; Sapkal, Gajanan N; Yadav, Pragya D

    2016-05-01

    The emergence of Zika virus (ZiV), a mosquito borne Flavivirus like dengue (DEN) and chikungunya (CHIK), in Brazil in 2014 and its spread to various countries have led to a global health emergency. Aedes aegypti is the major vector for ZiV. Fast dissemination of this virus in different geographical areas posses a major threat especially to regions where the population lacks herd immunity against the ZiV and there is abundance of Aedes mosquitoes. In this review, we focus on current global scenario, epidemiology, biology, diagnostic challenges and remedial measures for ZiVconsidering the Indian perspective.

  15. Viruses in reptiles

    Directory of Open Access Journals (Sweden)

    Ariel Ellen

    2011-09-01

    Full Text Available Abstract The etiology of reptilian viral diseases can be attributed to a wide range of viruses occurring across different genera and families. Thirty to forty years ago, studies of viruses in reptiles focused mainly on the zoonotic potential of arboviruses in reptiles and much effort went into surveys and challenge trials of a range of reptiles with eastern and western equine encephalitis as well as Japanese encephalitis viruses. In the past decade, outbreaks of infection with West Nile virus in human populations and in farmed alligators in the USA has seen the research emphasis placed on the issue of reptiles, particularly crocodiles and alligators, being susceptible to, and reservoirs for, this serious zoonotic disease. Although there are many recognised reptilian viruses, the evidence for those being primary pathogens is relatively limited. Transmission studies establishing pathogenicity and cofactors are likewise scarce, possibly due to the relatively low commercial importance of reptiles, difficulties with the availability of animals and permits for statistically sound experiments, difficulties with housing of reptiles in an experimental setting or the inability to propagate some viruses in cell culture to sufficient titres for transmission studies. Viruses as causes of direct loss of threatened species, such as the chelonid fibropapilloma associated herpesvirus and ranaviruses in farmed and wild tortoises and turtles, have re-focused attention back to the characterisation of the viruses as well as diagnosis and pathogenesis in the host itself. 1. Introduction 2. Methods for working with reptilian viruses 3. Reptilian viruses described by virus families 3.1. Herpesviridae 3.2. Iridoviridae 3.2.1 Ranavirus 3.2.2 Erythrocytic virus 3.2.3 Iridovirus 3.3. Poxviridae 3.4. Adenoviridae 3.5. Papillomaviridae 3.6. Parvoviridae 3.7. Reoviridae 3.8. Retroviridae and inclusion body disease of Boid snakes 3.9. Arboviruses 3.9.1. Flaviviridae 3

  16. Zika Virus

    Science.gov (United States)

    Zika is a virus that is spread mostly by mosquitoes. A pregnant mother can pass it to ... through blood transfusions. There have been outbreaks of Zika virus in the United States, Africa, Southeast Asia, ...

  17. Chikungunya virus

    Science.gov (United States)

    Chikungunya virus infection; Chikungunya ... Where Chikungunya is found Before 2013, the virus was found in Africa, Asia, Europe, and the Indian and Pacific oceans. In late 2013, outbreaks occurred for the first time in the ...

  18. Efficacy of CMX001 as a Post Exposure Antiviral in New Zealand White Rabbits Infected with Rabbitpox Virus, a Model for Orthopoxvirus Infections of Humans

    Directory of Open Access Journals (Sweden)

    Scott Foster

    2011-01-01

    Full Text Available CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxypropan-1-ol to cidofovir (CDV, is being developed as a treatment for smallpox. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Previously, we demonstrated the efficacy of CMX001 in protecting New Zealand White rabbits from mortality following intradermal infection with rabbitpox virus as a model for smallpox, monkeypox and for treatment of adverse reactions to smallpox vaccination. Here we extend these studies by exploring different dosing regimens and performing randomized, blinded, placebo-controlled studies. In addition, because rabbitpox virus can be transmitted via naturally generated aerosols (animal to animal transmission, we report on studies to test the efficacy of CMX001 in protecting rabbits from lethal rabbitpox virus disease when infection occurs by animal to animal transmission. In all cases, CMX001 treatment was initiated at the onset of observable lesions in the ears to model the use of CMX001 as a treatment for symptomatic smallpox. The results demonstrate that CMX001 is an effective treatment for symptomatic rabbitpox virus infection. The rabbitpox model has key similarities to human smallpox including an incubation period, generalized systemic disease, the occurrence of lesions which may be used as a trigger for initiating therapy, and natural animal to animal spread, making it an appropriate model.

  19. Establishment of Real-time Fluorescence PCR for Detection of Monkeypox Virus at Frontier Ports%国境口岸猴痘病毒实时荧光PCR检测方法的建立

    Institute of Scientific and Technical Information of China (English)

    李小波; 幸芦琴; 郑夔; 相大鹏

    2009-01-01

    [目的]建立快速、特异的猴痘病毒实时荧光PCR检测方法.[方法]制备猴痘病毒阳性样本,设计并合成相应的扩增引物及荧光标记探针,摸索最佳反应条件.[结果]本方法对模拟猴痘病毒样本的检测灵敏度达到102拷贝/反应.本方法快速、灵敏,并具有较高的特异性和重复性,可在3h内准确检测出猴痘病毒核酸.[结论]本方法适合国境口岸猴痘病毒快速检测,对防止猴痘病毒传入我国,保障我国的国境口岸卫生安全具有重要意义.

  20. CD8 T cells are essential for recovery from a respiratory vaccinia virus infection.

    Science.gov (United States)

    Goulding, John; Bogue, Rebecka; Tahiliani, Vikas; Croft, Michael; Salek-Ardakani, Shahram

    2012-09-01

    The precise immune components required for protection against a respiratory Orthopoxvirus infection, such as human smallpox or monkeypox, remain to be fully identified. In this study, we used the virulent Western Reserve strain of vaccinia virus (VACV-WR) to model a primary respiratory Orthopoxvirus infection. Naive mice infected with VACV-WR mounted an early CD8 T cell response directed against dominant and subdominant VACV-WR Ags, followed by a CD4 T cell and Ig response. In contrast to other VACV-WR infection models that highlight the critical requirement for CD4 T cells and Ig, we found that only mice deficient in CD8 T cells presented with severe cachexia, pulmonary inflammation, viral dissemination, and 100% mortality. Depletion of CD8 T cells at specified times throughout infection highlighted that they perform their critical function between days 4 and 6 postinfection and that their protective requirement is critically dictated by initial viral load and virulence. Finally, the ability of adoptively transferred naive CD8 T cells to protect RAG⁻/⁻ mice against a lethal VACV-WR infection demonstrated that they are both necessary and sufficient in protecting against a primary VACV-WR infection of the respiratory tract.

  1. Hyperthermophilic Archaeal Viruses as Novel Nanoplatforms

    DEFF Research Database (Denmark)

    Uldahl, Kristine Buch

    Viruses are the most abundant biological entities on earth, and with an estimated 1031 virus-like particles in the biosphere, viruses are virtually everywhere. Traditionally, the study of viruses has focused on their roles as infectious agents. However, over the last decades with the development...... of a broad range of genetic and chemical engineering methods, viral research has expanded. Viruses are now emerging as nanoplatforms with applications in materials science and medicine. A great challenge in biomedicine is the targeting of therapeutics to specific locations in the body in order to increase...... therapeutic benefit and minimize adverse effects. Virus-based nanoplatforms take advantage of the natural circulatory and targeting properties of viruses, to design therapeutics that specifically target tissues of interest in vivo. Plant-based viruses and bacteriophages are typically considered safer...

  2. Challenges of respondent driven sampling to assess sexual behaviour and estimate the prevalence of human immunodeficiency virus (HIV) and syphilis in men who have sex with men (MSM) in Singapore.

    Science.gov (United States)

    Chua, Arlene C; Chen, Mark Ic; Cavailler, Philippe; Jiang, Lili; Abdullah, Mohammed Ridzwan; Ng, Oon Tek; Chio, Martin; Koe, Stuart; Tay, Joanne; Wong, Mee Lian; Chan, Roy

    2013-07-01

    There is a lack of representative samples to provide reliable and accurate seroprevalence of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) as well as behavioural information among men who have sex with men (MSM) in Singapore. We used respondent driven sampling (RDS) to recruit MSM. Participants completed a survey used by Asian Internet MSM Sex Survey (AIMSS) and were tested for HIV and syphilis. We compared the characteristics of the RDS participants with STI diagnosis against those who did not have any STI diagnosis in the past 6 months. We compared RDS participants with AIMSS participants. Of 72 MSM recruited, 1 was positive for HIV (1.3%) and 4 (5.5%) tested positive for syphilis. Median age was 30 years and majority was Chinese (69.4%). RDS participants who had any STI diagnosis reported to have more use of recreational drugs (P = 0.006), and lower condom use (P = 0.054). Comparing RDS participants (n = 72) with the AIMSS participants (n = 2075), RDS respondents had ≥1 male partner in the past 6 months (P = 0.003), more casual sex partners (P = 0.012) and more STI symptoms (P = 0.019). There was no difference in terms of HIV testing and recreational drug use. The HIV and syphilis seroprevalence rates from our study are similar to previous reports conducted in high-risk MSM. In contrast to other settings, RDS did not work well among MSM in Singapore. The public health implications of our study highlight the challenges in obtaining data for HIV surveillance in assessing prevalence and risk behaviours among MSM.

  3. Influence of serotype and virus strain on synergism between Marek's disease vaccine viruses.

    Science.gov (United States)

    Witter, R L

    1992-12-01

    The enhanced protective effect (synergism) when certain Marek's disease (MD) vaccine viruses are combined has been widely used in the development of improved vaccines, but the mechanism is poorly understood. To better characterize the basis for synergism among MD vaccine viruses, three vaccine viruses from each of the three MD viral serotypes were evaluated alone and in various combinations for protection against early challenge with very virulent MD viruses in four replicate trials. Synergism seemed to be influenced by viral serotype because significant enhancement occurred frequently between viruses of serotypes 2 and 3 (five of nine bivalent vaccines positive), but rarely between viruses of serotypes 1 and 3 (one of nine bivalent vaccines positive) and 1 and 2 (one of nine bivalent vaccines positive), and was not detectable between viruses of the same serotype (none of nine bivalent vaccines positive). With some exceptions, the degree of synergism tended to vary inversely with the mean protective efficacy of the most protective component virus. Little effect of virus dose, virus dose ratio or type and route of viral challenge was noted. The combination of strains 281MI/1 (serotype 2) and WTHV-1/1 (serotype 3), both poorly protective as monovalent vaccines, consistently demonstrated high levels of synergism (over 300%) in antibody-positive chickens challenged 5 days post-vaccination with Md5 virus. This protocol may be a useful model system for further studies on mechanisms of synergism. However, mixtures that optimize synergism are not necessarily as protective as commercial vaccines.

  4. Chemical Modifications of Antisense Morpholino Oligomers Enhance Their Efficacy against Ebola Virus Infection

    Science.gov (United States)

    2009-05-01

    specific PMOs in infected cells and mice during lethal Ebola virus challenge. Members of the Filoviridae family of viruses , Ebola virus (EBOV) and Marburg ...American Society for Microbiology. All Rights Reserved. Chemical Modifications of Antisense Morpholino Oligomers Enhance Their Efficacy against Ebola Virus ...sequence is complementary to a region spanning the start codon of VP24 mRNA were protected against lethal Ebola virus challenge. In the present study, we

  5. 鸭肠炎病毒强毒参考株在感染鸭体内的动态分布研究%Dynamic Distribution of Duck Enteritis Virus Standard Challenge Strain in Experimentally Infected Ducklings

    Institute of Scientific and Technical Information of China (English)

    文晶亮; 李俊平; 李启红; 李岭; 孙淼; 李慧姣; 杨承槐; 夏业才

    2014-01-01

    为研究鸭肠炎病毒( DEV)强毒株在感染鸭体内的动态分布规律,根据DEV的gD基因序列设计检测引物RT-gDF和RT-gDR,建立了特异性强、敏感性高、重复性好的检测DEV的SYBR GreenⅠ实时荧光定量PCR方法。应用已建立的方法,对DEV强毒参考株感染鸭的组织脏器进行了定量检测。结果显示,接种后6 h即可在所有受检组织中检测到DEV DNA,随着病程发展, DNA拷贝数持续升高,直至接种5 d后感染鸭全部死亡。其中结肠病毒DNA拷贝数为最高,达到1013.26 copies/g,法氏囊、肝脏和盲肠次之,约1012 copies/g。证实了DEV强毒对感染鸭的免疫器官、神经组织和消化系统均具有广泛的嗜性。%To explore the dynamic distribution of duck enteritis virus challenge standard strain ( DEV CSC ) in experimentally infected ducklings, the specific primers ( RT-gDF and RT-gDR) were designed according to the gene DEV gD, and the SYBR GreenⅠreal-time fluorescent quantitative PCR method for virulent strain with satisfaction of specificity, sensibility and repeatability was established. Copies of DEV DNA were quantified in the collected tissues by the fluorescent quantitative PCR method. In result, DEV CSC DNA were firstly detected in all the samples at six hours after inoculation and the DNA copies subsequently continued to rise till the death of all the ducklings infected with DEV CSC virulent strain five days after inoculation. The DNA copies of DEV CSC strain in colon(1013.26 copies/g) of dead ducklings was highest, and then came to bursa of Fabricius, caecum and liver, about 1012 copies/g. The results above comfirmed that the virulent strain CSC had broad tissue tropism on immune organs, nerve tissue and digestive system of infected ducks.

  6. Computer Virus

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Computer viruses are small software programs that are designed to spread from one computerto another and to interfere with computer operation.A virus might delete data on your computer,use your e-mail program to spread itself to othercomputers,or even erase everything on your hard disk.Viruses are most easily spread by attach-ments in e-mail messages or instant messaging messages.That is why it is essential that you never

  7. Hyperthermophilic Archaeal Viruses as Novel Nanoplatforms

    DEFF Research Database (Denmark)

    Uldahl, Kristine Buch

    of a broad range of genetic and chemical engineering methods, viral research has expanded. Viruses are now emerging as nanoplatforms with applications in materials science and medicine. A great challenge in biomedicine is the targeting of therapeutics to specific locations in the body in order to increase...... nanoplatforms than mammalian viruses because they cannot proliferate in humans and hence are less likely to trigger adverse effects. Another group of viruses that fits this criterion is archaeal viruses yet their potential remains untapped. As a group, archaeal viruses offer distinct advantages such as unique...... hyperthermophilic archaeal viruses, SMV1 and SSV2 and cells of human origin. This chapter provides the first results demonstrating that archaeal viruses can be taken up and internalized by human cells, thus indicating a potential as intracellular delivery agents. Chapter III investigates SMV1 particles as potential...

  8. Viruses, virophages, and their living nature.

    Science.gov (United States)

    Ruiz-Saenz, J; Rodas, J D

    2010-01-01

    Over 100 years viruses have fascinated scientists around the world. Although biologists, chemists, physicians, veterinarians, and even physicists attempted to elucidate the nature of viruses, the question still remains "Are viruses alive?" Different theories have aimed at unifying our views of virology to provide an answer. However, the discovery of a mimivirus, its genome organization and replication cycle, in addition to the recently found virophage challenged the established frontier between viruses and parasitic cellular organisms. Consequently, the old controversy whether viruses are inert agents at the threshold of life or a different form of life was reignited. This review reopens the debate about the living nature of viruses from the classical concepts to the recent discoveries in order to rationally discuss our beliefs about the living or non-living character of viruses. filterable agent; mimivirus; virophage.

  9. Phytophthora viruses.

    Science.gov (United States)

    Cai, Guohong; Hillman, Bradley I

    2013-01-01

    Phytophthora sp. is a genus in the oomycetes, which are similar to filamentous fungi in morphology and habitat, but phylogenetically more closely related to brown algae and diatoms and fall in the kingdom Stramenopila. In the past few years, several viruses have been characterized in Phytophthora species, including four viruses from Phytophthora infestans, the late blight pathogen, and an endornavirus from an unnamed Phytophthora species from Douglas fir. Studies on Phytophthora viruses have revealed several interesting systems. Phytophthora infestans RNA virus 1 (PiRV-1) and PiRV-2 are likely the first members of two new virus families; studies on PiRV-3 support the establishment of a new virus genus that is not affiliated with established virus families; PiRV-4 is a member of Narnaviridae, most likely in the genus Narnavirus; and Phytophthora endornavirus 1 (PEV1) was the first nonplant endornavirus at the time of reporting. Viral capsids have not been found in any of the above-mentioned viruses. PiRV-1 demonstrated a unique genome organization that requires further examination, and PiRV-2 may have played a role in late blight resurgence in 1980s-1990s.

  10. Computer Virus

    Institute of Scientific and Technical Information of China (English)

    高振桥

    2002-01-01

    If you work with a computer,it is certain that you can not avoid dealing, with at least one computer virus.But how much do you know about it? Well,actually,a computer virus is not a biological' one as causes illnesses to people.It is a kind of computer program

  11. IMMUNE SUPPRESSION OF CHALLENGED VACCINATES AS A RIGOROUS ASSESSMENT OF STERILE PROTECTION BY LENTIVIRAL VACCINES

    Science.gov (United States)

    Craigo, Jodi K.; Durkin, Shannon; Sturgeon, Timothy J.; Tagmyer, Tara; Cook, Sheila J.; Issel, Charles J.; Montelaro, Ronald C.

    2007-01-01

    We previously reported that an experimental live-attenuated equine infectious anemia virus (EIAV) vaccine, containing a mutated S2 accessory gene, provided protection from disease and detectable infection after virulent virus (EIAVPV) challenge [1,2]. To determine if attenuated EIAV vaccines actually prevent persistent infection by challenge virus, we employed a 14-day dexamethasone treatment of vaccinated horses post-challenge to suppress host immunity and amplify replication levels of any infecting EIAV. At two months post-challenge the horses were all protected from virulent-virus challenge, evidenced by a lack of EIA signs and detectable challenge plasma viral RNA. Upon immune suppression, 6/12 horses displayed clinical EIA. Post-immune suppression characterizations demonstrated that the attenuated vaccine evidently prevented detectable challenge virus infection in 50% of horses. These data highlight the utility of post-challenge immune suppression for evaluating persistent viral vaccine protective efficacy. PMID:17023099

  12. Challenges and counter challenges in HIV/AIDS

    Institute of Scientific and Technical Information of China (English)

    Qingsheng Li; Charles Wood

    2010-01-01

    @@ Since the beginning of the HIV/AIDS pandemic, there has been significant progress in combating the virus.In addition to identifying HIV,1 scientists have developed an array of antiretroviral drugs and successfully converted the once deadly disease into a treatable and chronic condition.2 Nevertheless, this battle is far from over and HIV still outsmarts humans in multiple ways and poses tremendous challenges. Within this context, the Chinese Medical Journal has timely published this special issue on HIV/AIDS, highlighting the ongoing challenges posed by HIV and potential solutions to these problems.

  13. Viruses, definitions and reality

    Directory of Open Access Journals (Sweden)

    Libia Herrero-Uribe

    2011-09-01

    Full Text Available Viruses are known to be abundant, ubiquitous, and to play a very important role in the health and evolution of life organisms. However, most biologists have considered them as entities separate from the realm of life and acting merely as mechanical artifacts that can exchange genes between different organisms. This article reviews some definitions of life organisms to determine if viruses adjust to them, and additionally, considers new discoveries to challenge the present definition of viruses. Definitions of life organisms have been revised in order to validate how viruses fit into them. Viral factories are discussed since these mini-organelles are a good example of the complexity of viral infection, not as a mechanical usurpation of cell structures, but as a driving force leading to the reorganization and modification of cell structures by viral and cell enzymes. New discoveries such as the Mimivirus, its virophage and viruses that produce filamentous tails when outside of their host cell, have stimulated the scientific community to analyze the current definition of viruses. One way to be free for innovation is to learn from life, without rigid mental structures or tied to the past, in order to understand in an integrated view the new discoveries that will be unfolded in future research. Life processes must be looked from the complexity and trans-disciplinarity perspective that includes and accepts the temporality of the active processes of life organisms, their interdependency and interrelation among them and their environment. New insights must be found to redefine life organisms, especially viruses, which still are defined using the same concepts and knowledge of the fifties. Rev. Biol. Trop. 59 (3: 993-998. Epub 2011 September 01.Los virus son abundantes, ubicuos, y juegan un papel muy importante en la salud y en la evolución de los organismos vivos. Sin embargo, la mayoría de los biólogos los siguen considerado como entidades separadas

  14. Computer viruses

    Science.gov (United States)

    Denning, Peter J.

    1988-01-01

    The worm, Trojan horse, bacterium, and virus are destructive programs that attack information stored in a computer's memory. Virus programs, which propagate by incorporating copies of themselves into other programs, are a growing menace in the late-1980s world of unprotected, networked workstations and personal computers. Limited immunity is offered by memory protection hardware, digitally authenticated object programs,and antibody programs that kill specific viruses. Additional immunity can be gained from the practice of digital hygiene, primarily the refusal to use software from untrusted sources. Full immunity requires attention in a social dimension, the accountability of programmers.

  15. Pandemic Influenza Vaccines – The Challenges

    Directory of Open Access Journals (Sweden)

    Rebecca Cox

    2009-12-01

    Full Text Available Recent years’ enzootic spread of highly pathogenic H5N1 virus among poultry and the many lethal zoonoses in its wake has stimulated basic and applied pandemic vaccine research. The quest for an efficacious, affordable and timely accessible pandemic vaccine has been high on the agenda. When a variant H1N1 strain of swine origin emerged as a pandemic virus, it surprised many, as this subtype is well-known to man as a seasonal virus. This review will cover some difficult vaccine questions, such as the immunological challenges, the new production platforms, and the limited supply and global equity issues.

  16. The administration of a single dose of a multivalent (DHPPiL4R vaccine prevents clinical signs and mortality following virulent challenge with canine distemper virus, canine adenovirus or canine parvovirus

    Directory of Open Access Journals (Sweden)

    Stephen Wilson

    2014-01-01

    In conclusion, we demonstrated that a single administration of a minimum titre, multivalent vaccine to dogs of six weeks of age is efficacious and prevents clinical signs and mortality caused by CAV-1 and CDV; prevents clinical signs and significantly reduces virus shedding caused by CAV-2; and prevents clinical signs, leucopoenia and viral excretion caused by CPV.

  17. Challenged Pragmatism

    DEFF Research Database (Denmark)

    Christoffersen, Lisbet; Vinding, Niels Valdemar

    2013-01-01

    of religious faith have made religious claims and thereby challenged a secular understanding of the Danish labour market. This raises the question of the extent to which the religion of the individual can be accepted in the general public sphere. At the same time, religious ethos organisations have argued...

  18. Powassan (POW) Virus Basics

    Science.gov (United States)

    ... Professionals Related Topics For International Travelers Powassan (POW) Virus Basics Download this fact sheet formatted for print: ... POW) Virus Fact Sheet (PDF) What is Powassan virus? Powassan (POW) virus is a flavivirus that is ...

  19. Molecular Smallpox Vaccine Delivered by Alphavirus Replicons Elicits Protective Immunity in Mice and Non-human Primates

    Science.gov (United States)

    Hooper, Jay W.; Ferro, Anthony M.; Golden, Joseph W.; Silvera, Peter; Dudek, Jeanne; Alterson, Kim; Custer, Max; Rivers, Bryan; Morris, John; Owens, Gary; Smith, Jonathan F.; Kamrud, Kurt I.

    2009-01-01

    Naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 70s. Because of its highly contagious nature and high mortality rate, smallpox has significant potential as a biological weapon. Unfortunately, the current vaccine for orthopoxviruses is contraindicated for large portions of the population. Thus, there is a need for new, safe, and effective orthopoxvirus vaccines. Alphavirus replicon vectors, derived from strains of Venezuelan equine encephalitis virus, are being used to develop alternatives to the current smallpox vaccine. Here, we demonstrated that virus-like replicon particles (VRP) expressing the vaccinia virus A33R, B5R, A27L, and L1R genes elicited protective immunity in mice comparable to vaccination with live-vaccinia virus. Furthermore, cynomolgus macaques vaccinated with a combination of the four poxvirus VRPs (4pox-VRP) developed antibody responses to each antigen. These antibody responses were able to neutralize and inhibit the spread of both vaccinia virus and monkeypox virus. Macaques vaccinated with 4pox-VRP, flu HA VRP (negative control), or live-vaccinia virus (positive control) were challenged intravenously with 5 × 106 PFU of monkeypox virus 1 month after the second VRP vaccination. Four of the six negative control animals succumbed to monkeypox and the remaining two animals demonstrated either severe or grave disease. Importantly, all 10 macaques vaccinated with the 4pox-VRP vaccine survived without developing severe disease. These findings revealed that a single-boost VRP smallpox vaccine shows promise as a safe alternative to the currently licensed live-vaccinia virus smallpox vaccine. PMID:19833247

  20. Molecular smallpox vaccine delivered by alphavirus replicons elicits protective immunity in mice and non-human primates.

    Science.gov (United States)

    Hooper, Jay W; Ferro, Anthony M; Golden, Joseph W; Silvera, Peter; Dudek, Jeanne; Alterson, Kim; Custer, Max; Rivers, Bryan; Morris, John; Owens, Gary; Smith, Jonathan F; Kamrud, Kurt I

    2009-12-11

    Naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 1970s. Because of its highly contagious nature and high mortality rate, smallpox has significant potential as a biological weapon. Unfortunately, the current vaccine for orthopoxviruses is contraindicated for large portions of the population. Thus, there is a need for new, safe, and effective orthopoxvirus vaccines. Alphavirus replicon vectors, derived from strains of Venezuelan equine encephalitis virus, are being used to develop alternatives to the current smallpox vaccine. Here, we demonstrated that virus-like replicon particles (VRPs) expressing the vaccinia virus A33R, B5R, A27L, and L1R genes elicited protective immunity in mice comparable to vaccination with live-vaccinia virus. Furthermore, cynomolgus macaques vaccinated with a combination of the four poxvirus VRPs (4pox-VRP) developed antibody responses to each antigen. These antibody responses were able to neutralize and inhibit the spread of both vaccinia virus and monkeypox virus. Macaques vaccinated with 4pox-VRP, flu HA VRP (negative control), or live-vaccinia virus (positive control) were challenged intravenously with 5 x 10(6)pfu of monkeypox virus 1 month after the second VRP vaccination. Four of the six negative control animals succumbed to monkeypox and the remaining two animals demonstrated either severe or grave disease. Importantly, all 10 macaques vaccinated with the 4pox-VRP vaccine survived without developing severe disease. These findings revealed that a single-boost VRP smallpox vaccine shows promise as a safe alternative to the currently licensed live-vaccinia virus smallpox vaccine.

  1. Virus Diseases: The Global Challenge to Health for All. Asia-Pacific Congress of Medical Virology (2nd) Held in Bangkok, Thailand on November 17-22, 1991. Abstracts

    Science.gov (United States)

    1992-07-01

    fever virus was 1:1280. He was suspected of having systemic lupus erythematosus and epidemic hemorrhagic fever. Peripheral blood was taken 7 days before...with Ectopic Pregnancy Utidsak Hariralanakul, THAILAND 4. Diagnosis and Typing of Chlamydial Infections by the Polymerase Chain Reaction Suphat...CHLAMYDIAL AND GONOCOCCAL INFECTIONS WITH ECTOPIC PREGNANCY U. Harirattanakul, U. Kositanont?, C. Thirapakawong’, C. Was?, V. Gherunpong2 Departments of

  2. Proteção fetal frente a desafio com o vírus da Diarréia Viral Bovina (BVDV em ovelhas imunizadas com duas amostras de vírus modificadas experimentalmente Fetal protection against challenge with bovine viral diarrhea virus (BVDV in pregnant ewes immunized with two strains experimentally attenuated

    Directory of Open Access Journals (Sweden)

    Mário C.S. Brum

    2002-04-01

    virus (BVDV submitted to multiple passages in tissue culture associated with ultraviolet irradiation were evaluated as vaccine virus candidates. The attenuation of the modified viruses was assessed in calves and in pregnant ewes. Intramuscular inoculation of the viruses in four seronegative calves produced only a mild and transient rise in body temperature, followed by the production of high titers of neutralizing antibodies. The viruses were not detected in nasal secretions or in the blood following inoculation. However, intramuscular inoculation of these viruses in four pregnant ewes resulted in transplacental transmission and infection of all fetuses. To assess fetal protection conferred by immunization, pregnant ewes immunized twice with the modified viruses were subsequently challenged by intranasal inoculation of BVDV-1 (SV-126.8, n=6 or BVDV-2 (SV-260, n=5. At the day of challenge (134 days after the second immunization, all ewes had high titers of neutralizing antibodies (256 to >4096 to the vaccine viruses and variable titers (8 to >4096 to Brazilian BVDV-1 and BVDV-2 field isolates. Fifteen days after challenge, the ewes were euthanized and fetal tissues were examined for infectivity. All fetuses from non-vaccinated, challenged ewes (n=4 were infected. In contrast, none of the fetuses from the immunized dams (n=11 were positive for virus, indicating that the immunological response induced by immunization with the vaccine candidate viruses was capable of preventing fetal infection. These results indicate that it is possible to achieve fetal protection to BVDV by induction of a strong immunological response using modified live vaccines.

  3. Computer Viruses. Technology Update.

    Science.gov (United States)

    Ponder, Tim, Comp.; Ropog, Marty, Comp.; Keating, Joseph, Comp.

    This document provides general information on computer viruses, how to help protect a computer network from them, measures to take if a computer becomes infected. Highlights include the origins of computer viruses; virus contraction; a description of some common virus types (File Virus, Boot Sector/Partition Table Viruses, Trojan Horses, and…

  4. Simple technique for in field samples collection in the cases of skin rash illness and subsequent PCR detection of orthopoxviruses and varicella zoster virus.

    Directory of Open Access Journals (Sweden)

    Catherine Dumont

    Full Text Available BACKGROUND: In case of outbreak of rash illness in remote areas, clinically discriminating monkeypox (MPX from severe form of chickenpox and from smallpox remains a concern for first responders. OBJECTIVE: The goal of the study was therefore to use MPX and chickenpox outbreaks in Democratic Republic of Congo (DRC as a test case for establishing a rapid and specific diagnosis in affected remote areas. METHODS: In 2008 and 2009, successive outbreaks of presumed MPX skin rash were reported in Bena Tshiadi, Yangala and Ndesha healthcare districts of the West Kasai province (DRC. Specimens consisting of liquid vesicle dried on filter papers or crusted scabs from healing patients were sampled by first responders. A field analytical facility was deployed nearby in order to carry out a real-time PCR (qPCR assay using genus consensus primers, consensus orthopoxvirus (OPV and smallpox-specific probes spanning over the 14 kD fusion protein encoding gene. A PCR-restriction fragment length polymorphism was used on-site as backup method to confirm the presence of monkeypox virus (MPXV in samples. To complete the differential diagnosis of skin rash, chickenpox was tested in parallel using a commercial qPCR assay. In a post-deployment step, a MPXV-specific pyrosequencing was carried out on all biotinylated amplicons generated on-site in order to confirm the on-site results. RESULTS: Whereas MPXV proved to be the agent causing the rash illness outbreak in the Bena Tshiadi, VZV was the causative agent of the disease in Yangala and Ndesha districts. In addition, each on-site result was later confirmed by MPXV-specific pyrosequencing analysis without any discrepancy. CONCLUSION: This experience of rapid on-site dual use DNA-based differential diagnosis of rash illnesses demonstrates the potential of combining tests specifically identifying bioterrorism agents and agents causing natural outbreaks. This opens the way to rapid on-site DNA-based identification of a

  5. Mobility Challenges

    DEFF Research Database (Denmark)

    Jensen, Ole B.; Lassen, Claus

    2011-01-01

    This article takes point of departure in the challenges to understand the importance of contemporary mobility. The approach advocated is a cross-disciplinary one drawing on sociology, geography, urban planning and design, and cultural studies. As such the perspective is to be seen as a part of th...... mobilities. In particular the article discusses 1) the physical city, its infrastructures and technological hardware/software, 2) policies and planning strategies for urban mobility and 3) the lived everyday life in the city and the region.......This article takes point of departure in the challenges to understand the importance of contemporary mobility. The approach advocated is a cross-disciplinary one drawing on sociology, geography, urban planning and design, and cultural studies. As such the perspective is to be seen as a part...... of the so-called ‘mobility turn’ within social science. The perspective is illustrative for the research efforts at the Centre for Mobility and Urban Studies (C-MUS), Aalborg University. The article presents the contours of a theoretical perspective meeting the challenges to research into contemporary urban...

  6. Tunable and label-free virus enrichment for ultrasensitive virus detection using carbon nanotube arrays

    Science.gov (United States)

    Yeh, Yin-Ting; Tang, Yi; Sebastian, Aswathy; Dasgupta, Archi; Perea-Lopez, Nestor; Albert, Istvan; Lu, Huaguang; Terrones, Mauricio; Zheng, Si-Yang

    2016-01-01

    Viral infectious diseases can erupt unpredictably, spread rapidly, and ravage mass populations. Although established methods, such as polymerase chain reaction, virus isolation, and next-generation sequencing have been used to detect viruses, field samples with low virus count pose major challenges in virus surveillance and discovery. We report a unique carbon nanotube size-tunable enrichment microdevice (CNT-STEM) that efficiently enriches and concentrates viruses collected from field samples. The channel sidewall in the microdevice was made by growing arrays of vertically aligned nitrogen-doped multiwalled CNTs, where the intertubular distance between CNTs could be engineered in the range of 17 to 325 nm to accurately match the size of different viruses. The CNT-STEM significantly improves detection limits and virus isolation rates by at least 100 times. Using this device, we successfully identified an emerging avian influenza virus strain [A/duck/PA/02099/2012(H11N9)] and a novel virus strain (IBDV/turkey/PA/00924/14). Our unique method demonstrates the early detection of emerging viruses and the discovery of new viruses directly from field samples, thus creating a universal platform for effectively remediating viral infectious diseases. PMID:27730213

  7. Nuclear proteins hijacked by mammalian cytoplasmic plus strand RNA viruses

    Energy Technology Data Exchange (ETDEWEB)

    Lloyd, Richard E., E-mail: rlloyd@bcm.edu

    2015-05-15

    Plus strand RNA viruses that replicate in the cytoplasm face challenges in supporting the numerous biosynthetic functions required for replication and propagation. Most of these viruses are genetically simple and rely heavily on co-opting cellular proteins, particularly cellular RNA-binding proteins, into new roles for support of virus infection at the level of virus-specific translation, and building RNA replication complexes. In the course of infectious cycles many nuclear-cytoplasmic shuttling proteins of mostly nuclear distribution are detained in the cytoplasm by viruses and re-purposed for their own gain. Many mammalian viruses hijack a common group of the same factors. This review summarizes recent gains in our knowledge of how cytoplasmic RNA viruses use these co-opted host nuclear factors in new functional roles supporting virus translation and virus RNA replication and common themes employed between different virus groups. - Highlights: • Nuclear shuttling host proteins are commonly hijacked by RNA viruses to support replication. • A limited group of ubiquitous RNA binding proteins are commonly hijacked by a broad range of viruses. • Key virus proteins alter roles of RNA binding proteins in different stages of virus replication.

  8. Influence of maternally-derived antibodies in 6-week old dogs for the efficacy of a new vaccine to protect dogs against virulent challenge with canine distemper virus, adenovirus or parvovirus

    Directory of Open Access Journals (Sweden)

    Stephen Wilson

    2014-01-01

    In conclusion, two doses of the DHPPi/L4R vaccine administered to dogs from six weeks of age in the presence of maternal antibodies aided in the protection against virulent challenge with CDV, CAV-1 or CPV.

  9. Ebola Virus

    Directory of Open Access Journals (Sweden)

    Anusha Rangare Lakshman

    2015-09-01

    Full Text Available The disease Ebola takes its name from the Ebola River situated near a village in the Democratic Republic of Congo, where the disease first appeared in 1976. It is caused by a virus from the Filoviridae family (filovirus. The present outbreak of Ebola Virus Disease (EVD concerns four countries in West Africa, namely Guinea, Liberia, Sierra Leone and Nigeria till date. Further to widespread transmission of the disease, it has been declared as a Public Health Emergency of International Concern by the World Health Organisation on 8 August 2014. As of 4 August 2014, countries have reported 1,711 cases (1,070 confirmed, 436 probable, 205 suspect, including 932 deaths. This review paper enlightens about the awareness of Ebola virus and its preventive measures. [Archives Medical Review Journal 2015; 24(3.000: 296-305

  10. Dengue virus vaccine development.

    Science.gov (United States)

    Yauch, Lauren E; Shresta, Sujan

    2014-01-01

    Dengue virus (DENV) is a significant cause of morbidity and mortality in tropical and subtropical regions, causing hundreds of millions of infections each year. Infections range from asymptomatic to a self-limited febrile illness, dengue fever (DF), to the life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The expanding of the habitat of DENV-transmitting mosquitoes has resulted in dramatic increases in the number of cases over the past 50 years, and recent outbreaks have occurred in the United States. Developing a dengue vaccine is a global health priority. DENV vaccine development is challenging due to the existence of four serotypes of the virus (DENV1-4), which a vaccine must protect against. Additionally, the adaptive immune response to DENV may be both protective and pathogenic upon subsequent infection, and the precise features of protective versus pathogenic immune responses to DENV are unknown, complicating vaccine development. Numerous vaccine candidates, including live attenuated, inactivated, recombinant subunit, DNA, and viral vectored vaccines, are in various stages of clinical development, from preclinical to phase 3. This review will discuss the adaptive immune response to DENV, dengue vaccine challenges, animal models used to test dengue vaccine candidates, and historical and current dengue vaccine approaches.

  11. Data Challenges

    CERN Multimedia

    McCubbin, N A

    Some two years ago we planned a series of Data Challenges starting at the end of 2001. At the time, that seemed to be comfortingly far in the future... Well, as the saying goes, doesn't time fly when you are having fun! ATLAS Computing is now deep in the throes of getting the first Data Challenge (DC0) up and running. One of the main aims of DC0 is to have a software 'release' in which we can generate full physics events, track all particles through the detector, simulate the detector response, reconstruct the event, and study it, with appropriate data storage en route. As all software is "always 95% ready" (!), we have been able to do most of this, more or less, for some time. But DC0 forces us to have everything working, together, at the same time: a reality check. DC0 should finish early next year, and it will be followed almost immediately afterwards by DC1 (DC0 was foreseen as the 'check' for DC1). DC1 will last into the middle of 2002, and has two major goals. The first is generation, simulation, and r...

  12. Mucosal vaccination with an attenuated maedi-visna virus clone.

    Science.gov (United States)

    Pétursson, Gudmundur; Matthíasdóttir, Sigrídur; Svansson, Vilhjálmur; Andrésdóttir, Valgerdur; Georgsson, Gudmundur; Martin, Agnes H; Agnarsdóttir, Gudrún; Gísladóttir, Eygló; Arnadóttir, Steinunn; Högnadóttir, Svava; Jónsson, Stefán Ragnar; Andrésson, Olafur S; Torsteinsdóttir, Sigurbjörg

    2005-05-02

    Four sheep were infected intratracheally with an attenuated molecular clone of maedi-visna virus (MVV). All four became infected. Ten months later these sheep were challenged intratracheally with a genetically similar but pathogenic clone of MVV. Four unvaccinated sheep were infected simultaneously. All sheep became infected by the challenge virus. The vaccinated sheep were not protected against superinfection with the challenge clone. However, virus was isolated more frequently from the blood of the unvaccinated controls than of the vaccinated animals and ten times more frequently from lungs of unvaccinated sheep than from lungs of vaccinated sheep at sacrifice, indicating partial protection.

  13. Interferon-γ Inhibits Ebola Virus Infection

    OpenAIRE

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. F...

  14. HUMAN PAPILLOMA VIRUS — ONCOGENIC VIRUS

    Directory of Open Access Journals (Sweden)

    A.N. Mayansky

    2010-01-01

    Full Text Available The lecture is devoted to oncogenic viruses, particularly human papilloma virus. Papilloma viral infection is found in all parts of the globe and highly contagious. In addition to exhaustive current data on classification, specifics of papilloma viruses composition and epidemiology, the author describes in great detail the malignization mechanisms of papilloma viruses pockets. Also, issues of diagnostics and specific prevention and treatment of diseases caused by this virus are illustrated. Key words: oncogenic viruses, papilloma viruses, prevention, vaccination. (Pediatric Pharmacology. – 2010; 7(4:48-55

  15. Evidence of mixed persistent infections in calves born to cows challenged with a pool of bovine viral diarrhea virus isolates Evidências de infecção persistente mista em bezerros nascidos de vacas inoculadas com um pool de isolados do vírus da diarréia viral bovina

    Directory of Open Access Journals (Sweden)

    Sandra Arenhart

    2010-12-01

    Full Text Available Pregnant cows infected with noncytopathic (NCP isolates of bovine viral diarrhea virus (BVDV between days 40 and 120 days of gestation frequently deliver immunotolerant, persistently infected (PI calves. We herein report the characterization of PI calves produced experimentally through inoculation of pregnant cows with a pool of Brazilian BVDV-1 (n=2 and BVDV-2 isolates (n=2 between days 60 and 90 of gestation. Two calves were born virus positive, lacked BVDV antibodies, but died 7 and 15 days after birth, respectively. Six other calves were born healthy, seronegative to BVDV, harbored and shed virus in secretions for up to 210 days. Analysis of the antigenic profile of viruses infecting these calves at birth and 30 days later with a panel of monoclonal antibodies indicated two patterns of infection. Whereas three calves apparently harbored only one isolate (either a BVDV-1 or BVDV-2, co-infection by two antigenically distinct challenge viruses was demonstrated in three PI calves. Moreover, testing the viruses obtained from the blood of PI calves by an RT-PCR able to differentiate between BVDV-1 and BVDV-2 confirmed the presence/persistence of two co-infecting viruses of different genotypes (BVDV-1 and BVDV-2 in these animals. These findings indicate that persistent infection of fetuses/calves - a well characterized consequence of fetal infection by BVDV - may be established concomitantly by more than one isolate, upon experimental inoculation. In this sense, mixed persistent infections with antigenically distinct isolates may help in understanding the immunological and molecular basis of BVDV immunotolerance and persistence.Vacas prenhes infectadas com isolados não-citopáticos (NCP do vírus da diarréia viral bovina (BVDV entre os dias 40 e 120 de gestação frequentemente produzem bezerros imunotolerantes, persistentemente infectados (PI. Este artigo relata a caracterização de bezerros PI produzidos experimentalmente, pela inoculação de

  16. SPS Challenges

    CERN Document Server

    Chapochnikova, Elena

    2008-01-01

    In future the SPS should be able to transfer to the LHC the beam produced by a completely new pre-injector chain and required by the LHC for different upgrade scenarios. The issues related to this extremely challenging task are presented together with some possible ways of overcoming the problems that arise. Besides an increase in injection energy provided by PS2, these measures can include both an SPS vacuum chamber upgrade against the e-cloud and operation with larger longitudinal emittance for beam stability. As a result the power plant of the SPS RF system must be doubled. The SPS upgrade will also need the improvement or replacement of many other machine elements.

  17. Oropuche virus: A virus present but ignored

    Directory of Open Access Journals (Sweden)

    Salim Mattar V.

    2015-09-01

    Full Text Available Bunyaviruses are RNA viruses that affect animals and plants; they have five genera and four of them affect humans: Orthobunyavirus, Nairovirus, Phlebovirus and Hantavirus. All of them are Arbovirus, except Hantavirus. The Orthobunyaviruses comprise Oropouche, Tahyna, La Crosse virus, California encephalitis virus and Heartland virus recently discovered (1. Except for Heartland virus which is transmitted by ticks of the genus Amblyoma, these Phleboviruses have as vectors mosquitoes, which bite small mammals which are able to be as reservoirs amplifiers.

  18. Innate immune recognition of hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    Hong-Yan; Liu; Xiao-Yong; Zhang

    2015-01-01

    Hepatitis B virus(HBV) is a hepatotropic DNA virus and its infection results in acute or chronic hepatitis. It is reported that the host innate immune system contributes to viral control and liver pathology, while whether and how HBV can trigger the components of innate immunity remains controversial. In recent years, the data accumulated from HBV-infected patients, cellular and animal models have challenged the concept of a stealth virus for HBV infection. This editorial focuses on the current findings about the innate immune recognition to HBV. Such evaluation could help us to understand HBV immunopathogenesis and develop novel immune therapeutic strategies to combat HBV infection.

  19. Breastfeeding, breast milk and viruses

    OpenAIRE

    Glenn Wendy K; Heads Joy; Lawson James S; Whitaker Noel J

    2007-01-01

    Abstract Background There is seemingly consistent and compelling evidence that there is no association between breastfeeding and breast cancer. An assumption follows that milk borne viruses cannot be associated with human breast cancer. We challenge this evidence because past breastfeeding studies did not determine "exposure" of newborn infants to colostrum and breast milk. Methods We conducted a prospective review of 100 consecutive births of infants in the same centre to determine the propo...

  20. Understanding Zika virus pathogenesis: an interview with Catherine Spong.

    Science.gov (United States)

    Spong, Catherine Y

    2016-06-06

    A recent outbreak of Zika virus has been linked to fetal abnormalities in pregnant women who have been infected. The scientific community is working toward understanding Zika virus pathogenesis to better manage affected women and children. In an interview with Dr. Catherine Spong, we discuss the aims and challenges of a forthcoming longitudinal study of a cohort of pregnant women in areas of current active Zika virus transmission.

  1. Scrapheap Challenge

    CERN Multimedia

    2004-01-01

    Three British guys at CERN recently took a break from work to try their hand at Scrapheap Challenge. Shown on Channel 4 in the UK, it is a show where two teams must construct a machine for a specific task using only the junk they can scavenge from the scrap yard around them. And they have just 10 hours to build their contraption before it is put to the test. The first round, aired 19 September, pitted a team of three women, from the British Army's Royal Electrical and Mechanical Engineers, against the CERN guys - the Up 'n Atoms: Ali Day, David McFarlane and James Ridewood. Each team, with the help of an appointed expert, had the task of making a giant, 3-metre self-propelled "bowling ball", to roll down a 50 metre bowling alley at skittles 4 metres high. The Up 'n Atoms' contraption featured a small car with a huge wheel on its back. Once up to speed, slamming on the brakes caused the wheel to roll over and take the car with it. On their very last run they managed to take out seven pins. Luckily, though, ...

  2. Plant Virus Metagenomics: Advances in Virus Discovery.

    Science.gov (United States)

    Roossinck, Marilyn J; Martin, Darren P; Roumagnac, Philippe

    2015-06-01

    In recent years plant viruses have been detected from many environments, including domestic and wild plants and interfaces between these systems-aquatic sources, feces of various animals, and insects. A variety of methods have been employed to study plant virus biodiversity, including enrichment for virus-like particles or virus-specific RNA or DNA, or the extraction of total nucleic acids, followed by next-generation deep sequencing and bioinformatic analyses. All of the methods have some shortcomings, but taken together these studies reveal our surprising lack of knowledge about plant viruses and point to the need for more comprehensive studies. In addition, many new viruses have been discovered, with most virus infections in wild plants appearing asymptomatic, suggesting that virus disease may be a byproduct of domestication. For plant pathologists these studies are providing useful tools to detect viruses, and perhaps to predict future problems that could threaten cultivated plants.

  3. Experimental fossilisation of viruses from extremophilic Archaea

    Directory of Open Access Journals (Sweden)

    F. Orange

    2011-06-01

    Full Text Available The role of viruses at different stages of the origin of life has recently been reconsidered. It appears that viruses may have accompanied the earliest forms of life, allowing the transition from an RNA to a DNA world and possibly being involved in the shaping of tree of life in the three domains that we know presently. In addition, a large variety of viruses has been recently identified in extreme environments, hosted by extremophilic microorganisms, in ecosystems considered as analogues to those of the early Earth. Traces of life on the early Earth were preserved by the precipitation of silica on the organic structures. We present the results of the first experimental fossilisation by silica of viruses from extremophilic Archaea (SIRV2 – Sulfolobus islandicus rod-shaped virus 2, TPV1 – Thermococcus prieurii virus 1, and PAV1 – Pyrococcus abyssi virus 1. Our results confirm that viruses can be fossilised, with silica precipitating on the different viral structures (proteins, envelope over several months in a manner similar to that of other experimentally and naturally fossilised microorganisms. This study thus suggests that viral remains or traces could be preserved in the rock record although their identification may be challenging due to the small size of the viral particles.

  4. Zika Virus and Pregnancy

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus ... Patient Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your ...

  5. Zika Virus and Pregnancy

    Medline Plus

    Full Text Available ... Management Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus ... Patient Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your ...

  6. Zika Virus and Pregnancy

    Medline Plus

    Full Text Available ... Management Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus ... Patient Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your ...

  7. Zika Virus and Pregnancy

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus ... Patient Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your ...

  8. Zika Virus and Pregnancy

    Medline Plus

    Full Text Available ... Management Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus and ... Patient Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your fetus ...

  9. Newcastle Disease Virus (PDQ)

    Science.gov (United States)

    ... Professionals Questions to Ask about Your Treatment Research Newcastle Disease Virus (PDQ®)–Patient Version Overview Go to ... cancer (see Question 8 ). Questions and Answers About Newcastle Disease Virus What is Newcastle disease virus? Newcastle ...

  10. Zika Virus and Pregnancy

    Medline Plus

    Full Text Available ... Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus and Pregnancy Page ... Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your fetus if you ...

  11. Respiratory Syncytial Virus

    Science.gov (United States)

    ... share with twitter share with linkedin Respiratory Syncytial Virus (RSV) Respiratory syncytial virus, or RSV, is a ... States. Why Is the Study of Respiratory Syncytial Virus (RSV) a Priority for NIAID? In the United ...

  12. Computer Viruses: An Overview.

    Science.gov (United States)

    Marmion, Dan

    1990-01-01

    Discusses the early history and current proliferation of computer viruses that occur on Macintosh and DOS personal computers, mentions virus detection programs, and offers suggestions for how libraries can protect themselves and their users from damage by computer viruses. (LRW)

  13. Virus Ebola Asia

    Directory of Open Access Journals (Sweden)

    Suharyono Wuryadi

    2012-09-01

    Full Text Available Virus Marburg dan Ebola diklasifikasikan sebagai virus yang sangat menular dan dimasukkan dalam klasifikasi sebagai virus/pathogen dengan derajat biosafety 4, sehingga untuk menanganinya diperlukan laboratorium khusus tingkat 4.

  14. Zika Virus and Pregnancy

    Medline Plus

    Full Text Available ... Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus and ... Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your fetus ...

  15. A new model for simulating evolution of human influenza virus

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Understanding the evolution of influenza A virus, which poses a global challenge to public health, is of special significance for its control and prevention. Although the genome structure of the virus is seemingly simple, their evolutionary patterns and molecular mechanisms are difficult to reveal.

  16. Ecogenomics and potential biogeochemical impacts of globally abundant ocean viruses

    NARCIS (Netherlands)

    Roux, Simon; Brum, Jennifer R; Dutilh, Bas E|info:eu-repo/dai/nl/304546313; Sunagawa, Shinichi; Duhaime, Melissa B; Loy, Alexander; Poulos, Bonnie T; Solonenko, Natalie; Lara, Elena; Poulain, Julie; Pesant, Stéphane; Kandels-Lewis, Stefanie; Dimier, Céline; Picheral, Marc; Searson, Sarah; Cruaud, Corinne; Alberti, Adriana; Duarte, Carlos M; Gasol, Josep M; Vaqué, Dolors

    2016-01-01

    Ocean microbes drive biogeochemical cycling on a global scale. However, this cycling is constrained by viruses that affect community composition, metabolic activity, and evolutionary trajectories. Owing to challenges with the sampling and cultivation of viruses, genome-level viral diversity remains

  17. IVA: accurate de novo assembly of RNA virus genomes.

    Science.gov (United States)

    Hunt, Martin; Gall, Astrid; Ong, Swee Hoe; Brener, Jacqui; Ferns, Bridget; Goulder, Philip; Nastouli, Eleni; Keane, Jacqueline A; Kellam, Paul; Otto, Thomas D

    2015-07-15

    An accurate genome assembly from short read sequencing data is critical for downstream analysis, for example allowing investigation of variants within a sequenced population. However, assembling sequencing data from virus samples, especially RNA viruses, into a genome sequence is challenging due to the combination of viral population diversity and extremely uneven read depth caused by amplification bias in the inevitable reverse transcription and polymerase chain reaction amplification process of current methods. We developed a new de novo assembler called IVA (Iterative Virus Assembler) designed specifically for read pairs sequenced at highly variable depth from RNA virus samples. We tested IVA on datasets from 140 sequenced samples from human immunodeficiency virus-1 or influenza-virus-infected people and demonstrated that IVA outperforms all other virus de novo assemblers. The software runs under Linux, has the GPLv3 licence and is freely available from http://sanger-pathogens.github.io/iva © The Author 2015. Published by Oxford University Press.

  18. High-throughput screening of viral entry inhibitors using pseudotyped virus.

    Science.gov (United States)

    Basu, Arnab; Mills, Debra M; Bowlin, Terry L

    2010-12-01

    Virus entry into a host cell is an attractive target for therapy because propagation of virus can be blocked at an early stage, minimizing chances for the virus to acquire drug resistance. Anti-infective drug discovery for BSL-4 viruses like Ebola or Lassa hemorrhagic fever virus presents challenges due to the requirement for a BSL-4 laboratory containment facility. Pseudotyped viruses provide a surrogate model in which the native envelope glycoprotein of a BSL-2 level virus (e.g., vesicular stomatitis virus) is replaced with envelope glycoprotein of a foreign BSL-4 virus (e.g., Ebola virus). Because the envelope glycoprotein determines interaction of virus with its cellular receptors, pseudotyped viruses can mimic the viral entry process of the original virus. Moreover, they are competent for only a single cycle of infection, and therefore can be used in BSL-2 facilities. Pseudotyped viruses have been used in high-throughput screening of entry inhibitors for a number of BSL-4 level viruses. This unit includes protocols for preparing pseudotyped viruses using lentiviral vectors and use of pseudotyped viruses for high-throughput screening of viral entry inhibitors.

  19. Characterization of Nora Virus Structural Proteins via Western Blot Analysis

    Directory of Open Access Journals (Sweden)

    Brad L. Ericson

    2016-01-01

    Full Text Available Nora virus is a single stranded RNA picorna-like virus with four open reading frames (ORFs. The coding potentials of the ORFs are not fully characterized, but ORF3 and ORF4 are believed to encode the capsid proteins (VP3, VP4a, VP4b, and VP4c comprising the virion. To determine the polypeptide composition of Nora virus virions, polypeptides from purified virus were compared to polypeptides detected in Nora virus infected Drosophila melanogaster. Nora virus was purified from infected flies and used to challenge mice for the production of antisera. ORF3, ORF4a, ORF4b, and ORF4c were individually cloned and expressed in E. coli; resultant recombinant proteins purified and were used to make monospecific antisera. Antisera were evaluated via Western blot against whole virus particles and Nora virus infected fly lysates. Viral purification yielded two particle types with densities of ~1.31 g/mL (empty particles and ~1.33 g/mL (complete virions. Comparison of purified virus polypeptide composition to Nora virus infected D. melanogaster lysate showed the number of proteins in infected cell lysates is less than purified virus. Our results suggest the virion is composed of 6 polypeptides, VP3, VP4a, two forms of VP4b, and two forms of VP4c. This polypeptide composition is similar to other small RNA insect viruses.

  20. Oncogenic viruses and cancer

    Institute of Scientific and Technical Information of China (English)

    Guangxiang; George; Luo; Jing-hsiung; James; Ou

    2015-01-01

    <正>This special issue of the journal is dedicated to the important topic of oncogenic viruses and cancer.It contains seven review articles covering all known oncogenic viruses except for human T-lymphotropic virus type1(HTLV-1).These review articles are contributed by experts on specific viruses and their associated human cancers.Viruses account for about 20%of total human cancer cases.Although many viruses can cause various tumors in animals,only seven of them

  1. Protection against Multiple Subtypes of Influenza Viruses by Virus-Like Particle Vaccines Based on a Hemagglutinin Conserved Epitope

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    Shaoheng Chen

    2015-01-01

    Full Text Available We selected the conserved sequence in the stalk region of influenza virus hemagglutinin (HA trimmer, the long alpha helix (LAH, as the vaccine candidate sequence, and inserted it into the major immunodominant region (MIR of hepatitis B virus core protein (HBc, and, by using the E. coli expression system, we prepared a recombinant protein vaccine LAH-HBc in the form of virus-like particles (VLP. Intranasal immunization of mice with this LAH-HBc VLP plus cholera toxin B subunit with 0.2% of cholera toxin (CTB* adjuvant could effectively elicit humoral and cellular immune responses and protect mice against a lethal challenge of homologous influenza viruses (A/Puerto Rico/8/1934 (PR8 (H1N1. In addition, passage of the immune sera containing specific antibodies to naïve mice rendered them resistant against a lethal homologous challenge. Immunization with LAH-HBc VLP vaccine plus CTB* adjuvant could also fully protect mice against a lethal challenge of the 2009 pandemic H1N1 influenza virus or the avian H9N2 virus and could partially protect mice against a lethal challenge of the avian H5N1 influenza virus. This study demonstrated that the LAH-HBc VLP vaccine based on a conserved sequence of the HA trimmer stalk region is a promising candidate vaccine for developing a universal influenza vaccine against multiple influenza viruses infections.

  2. Understanding viruses: Philosophical investigations.

    Science.gov (United States)

    Pradeu, Thomas; Kostyrka, Gladys; Dupré, John

    2016-10-01

    Viruses have been virtually absent from philosophy of biology. In this editorial introduction, we explain why we think viruses are philosophically important. We focus on six issues (the definition of viruses, the individuality and diachronic identity of a virus, the possibility to classify viruses into species, the question of whether viruses are living, the question of whether viruses are organisms, and finally the biological roles of viruses in ecology and evolution), and we show how they relate to classic questions of philosophy of biology and even general philosophy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Suitability of vaccinia virus and bovine viral diarrhea virus (BVDV for determining activities of three commonly-used alcohol-based hand rubs against enveloped viruses

    Directory of Open Access Journals (Sweden)

    Steinmann Jochen

    2007-02-01

    Full Text Available Abstract Background A procedure for including activity against enveloped viruses in the post-contamination treatment of hands has been recommended, but so far no European standard is available to implement it. In 2004, the German Robert Koch-Institute (RKI and the German Association for the Control of Virus Disease (DVV suggested that vaccinia virus and bovine viral diarrhea virus (BVDV should be used as test viruses in a quantitative suspension test to determine the activity of a disinfectant against all enveloped viruses. Methods We have studied the activities of three commonly-used alcohol-based hand rubs (hand rub A, based on 45% propan-2-ol, 30% propan-1-ol and 0.2% mecetronium etilsulfate; hand rub B, based on 80% ethanol; hand rub C, based on 95% ethanol against vaccinia virus and BVDV, and in addition against four other clinically relevant enveloped viruses: herpes simplex virus (HSV types 1 and 2, and human and avian influenza A virus. The hand rubs were challenged with different organic loads at exposure time of 15, 30 and 60 s. According to the guidelines of both BGA/RKI and DVV, and EN 14476:2005, the reduction of infectivity of each test virus was measured on appropriate cell lines using a quantitative suspension test. Results All three alcohol-based hand rubs reduced the infectivity of vaccinia virus and BVDV by ≥ 4 log10-steps within 15 s, irrespective of the type of organic load. Similar reductions of infectivity were seen against the other four enveloped viruses within 15 s in the presence of different types of organic load. Conclusion Commonly used alcohol-based hand rubs with a total alcohol concentration ≥ 75% can be assumed to be active against clinically relevant enveloped viruses if they effectively reduce the infectivities of vaccinia virus and BVDV in a quantitative suspension test.

  4. Autologous antibody capture to enrich immunogenic viruses for viral discovery.

    Science.gov (United States)

    Oude Munnink, Bas B; Jazaeri Farsani, Seyed Mohammad; Deijs, Martin; Jonkers, Jiri; Verhoeven, Joost T P; Ieven, Margareta; Goossens, Herman; de Jong, Menno D; Berkhout, Ben; Loens, Katherine; Kellam, Paul; Bakker, Margreet; Canuti, Marta; Cotten, Matthew; van der Hoek, Lia

    2013-01-01

    Discovery of new viruses has been boosted by novel deep sequencing technologies. Currently, many viruses can be identified by sequencing without knowledge of the pathogenicity of the virus. However, attributing the presence of a virus in patient material to a disease in the patient can be a challenge. One approach to meet this challenge is identification of viral sequences based on enrichment by autologous patient antibody capture. This method facilitates identification of viruses that have provoked an immune response within the patient and may increase the sensitivity of the current virus discovery techniques. To demonstrate the utility of this method, virus discovery deep sequencing (VIDISCA-454) was performed on clinical samples from 19 patients: 13 with a known respiratory viral infection and 6 with a known gastrointestinal viral infection. Patient sera was collected from one to several months after the acute infection phase. Input and antibody capture material was sequenced and enrichment was assessed. In 18 of the 19 patients, viral reads from immunogenic viruses were enriched by antibody capture (ranging between 1.5x to 343x in respiratory material, and 1.4x to 53x in stool). Enriched reads were also determined in an identity independent manner by using a novel algorithm Xcompare. In 16 of the 19 patients, 21% to 100% of the enriched reads were derived from infecting viruses. In conclusion, the technique provides a novel approach to specifically identify immunogenic viral sequences among the bulk of sequences which are usually encountered during virus discovery metagenomics.

  5. Natural history and treatment of hepatitis B virus and hepatitis C virus coinfection

    Directory of Open Access Journals (Sweden)

    Keeffe Emmet B

    2005-09-01

    Full Text Available Abstract Hepatitis B virus (HBV and hepatitis C virus (HCV coinfection is not uncommon as a result of similar routes of infection. Patients who are coinfected represent a unique group with diverse serologic profiles. Combined chronic hepatitis B and C leads to more severe liver disease and an increased risk of hepatocellular carcinoma. Furthermore, coinfected patients represent a treatment challenge. No standard recommendations exist for treatment of viral hepatitis due to dual HBV/HCV infection, and therefore treatment must be individualized based on patient variables such as serologic and virologic profiles, patient's prior exposure to antiviral treatment, and the presence of other parenterally transmitted viruses such as hepatitis D virus and human immunodeficiency virus. The natural history and treatment of patients with HBV and HCV coinfection is reviewed.

  6. Giant viruses in the oceans: the 4th Algal Virus Workshop

    Directory of Open Access Journals (Sweden)

    Claverie Jean-Michel

    2005-06-01

    Full Text Available Abstract Giant double-stranded DNA viruses (such as record breaking Acanthamoeba polyphaga Mimivirus, with particle sizes of 0.2 to 0.6 μm, genomes of 300 kbp to 1.200 kbp, and commensurate complex gene contents, constitute an evolutionary mystery. They challenge the common vision of viruses, traditionally seen as highly streamlined genomes optimally fitted to the smallest possible -filterable- package. Such giant viruses are now discovered in increasing numbers through the systematic sampling of ocean waters as well as freshwater aquatic environments, where they play a significant role in controlling phyto- and bacterio- plankton populations. The 4th algal virus workshop showed that the study of these ecologically important viruses is now massively entering the genomic era, promising a better understanding of their diversity and, hopefully, some insights on their origin and the evolutionary forces that shaped their genomes.

  7. RNA chaperones encoded by RNA viruses

    Institute of Scientific and Technical Information of China (English)

    Jie Yang; Hongjie Xia; Qi Qian; Xi Zhou

    2015-01-01

    RNAs are functionally diverse macromolecules whose proper functions rely strictly upon their correct tertiary structures. However, because of their high structural flexibility, correct folding of RNAs is challenging and slow. Therefore, cells and viruses encode a variety of RNA remodeling proteins, including helicases and RNA chaperones. In RNA viruses, these proteins are believed to play pivotal roles in all the processes involving viral RNAs during the life cycle. RNA helicases have been studied extensively for decades, whereas RNA chaperones, particularly virus-encoded RNA chaperones, are often overlooked. This review describes the activities of RNA chaperones encoded by RNA viruses, particularly the ones identified and characterized in recent years, and the functions of these proteins in different steps of viral life cycles, and presents an overview of this unique group of proteins.

  8. Inactivated Schmallenberg virus prototype vaccines.

    Science.gov (United States)

    Wernike, Kerstin; Nikolin, Veljko M; Hechinger, Silke; Hoffmann, Bernd; Beer, Martin

    2013-08-02

    Schmallenberg virus (SBV), a novel Orthobunyavirus, is an insect-transmitted pathogen and was first described in Europe in 2011. SBV causes a mild transient disease in adult ruminants, but severe foetal malformation and stillbirth were observed after an infection of naive cows and ewes, which is responsible for considerable economic losses. The virus is now widely distributed in Europe, and no vaccines were available to stop transmission and spread. In the present study, 16 calves and 25 sheep, the major target species of SBV infection, were vaccinated twice 3 weeks apart with one of 5 newly developed, inactivated vaccine candidates. Six calves and 5 sheep were kept as unvaccinated controls. All animals were clinically, serologically and virologically examined before and after challenge infection. Immunisation with the inactivated preparations resulted in a neutralising antibody response three weeks after the second vaccination without any side effects. The number of animals that seroconverted in each group and the strength of the antibody response were dependent on the cell line used for virus growth and on the viral titre prior to inactivation. Four vaccine prototypes completely prevented RNAemia after challenge infection, a fifth candidate reduced RNAemia considerably. Although further evaluations e.g. regarding duration of immunity will be necessary, the newly developed vaccines are promising candidates for the prevention of SBV-infection and could be a valuable tool in SBV control strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Oncolytic viruses as anticancer vaccines

    Directory of Open Access Journals (Sweden)

    Norman eWoller

    2014-07-01

    Full Text Available Oncolytic virotherapy has shown impressive results in preclinical studies and first promising therapeutic outcomes in clinical trials as well. Since viruses are known for a long time as excellent vaccination agents, oncolytic viruses are now designed as novel anticancer agents combining the aspect of lysis-dependent cytoreductive activity with concomitant induction of antitumoral immune responses. Antitumoral immune activation by oncolytic virus infection of tumor tissue comprises both, immediate effects of innate immunity and also adaptive responses for long lasting antitumoral activity which is regarded as the most prominent challenge in clinical oncology. To date, the complex effects of a viral tumor infection on the tumor microenvironment and the consequences for the tumor-infiltrating immune cell compartment are poorly understood. However, there is more and more evidence that a tumor infection by an oncolytic virus opens up a number of options for further immunomodulating interventions such as systemic chemotherapy, generic immunostimulating strategies, dendritic cell-based vaccines, and antigenic libraries to further support clinical efficacy of oncolytic virotherapy.

  10. HIV Immunotherapy: Host Immunity and Virus Evolution

    NARCIS (Netherlands)

    A.L. de Goede (Anna)

    2014-01-01

    markdownabstract__Abstract__ HIV-1 infection poses a major challenge to global public health. In spite of its huge clinical benefits, combined antiretroviral therapy fails to eradicate the virus from the body. Therefore, in the absence of a safe and effective preventive vaccine, HIV-specific

  11. Defective interfering virus protects elderly mice from influenza

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    Easton Andrew J

    2011-05-01

    Full Text Available Abstract Background We have identified and characterised a defective-interfering (DI influenza A virus particles containing a highly deleted segment 1 RNA that has broad-spectrum antiviral activity. In young adult mice it exerts protection against several different subtypes of influenza A virus (defined here as homologous or genetically compatible protection and against a paramyxovirus and an influenza B virus (heterologous or genetically unrelated protection. Homologous protection is mediated by replication competition between the deleted and full-length genomes, and heterologous protection occurs through stimulation of innate immunity, especially interferon type I. Methods A single dose of the protective DI virus was administered intranasally to elderly mice at -7, -1 and +1 days relative to intranasal challenge with influenza A virus. Results A single dose of the DI virus given 1 or 7 days protected elderly mice, reducing a severe, sometimes fatal disease to a subclinical or mild infection. In contrast, all members of control groups treated with inactivated DI virus before challenge became extremely ill and most died. Despite the subclinical/mild nature of their infection, protected mice developed solid immunity to a second infectious challenge. Conclusions The defective interfering virus is effective in preventing severe influenza A in elderly mice and may offer a new approach to protection of the human population.

  12. HIV-1 Polymorphism: a Challenge for Vaccine Development - A Review

    Directory of Open Access Journals (Sweden)

    Morgado MG

    2002-01-01

    Full Text Available The perspective for the development of anti-HIV/AIDS vaccines became a target sought by several research groups and pharmaceutical companies. However, the complex virus biology in addition to a striking genetic variability and the limited understanding of the immunological correlates of protection have made this an enormous scientific challenge not overcome so far. In this review we presented an updating of HIV-1 subtypes and recombinant viruses circulating in South American countries, focusing mainly on Brazil, as one of the challenges for HIV vaccine development. Moreover, we discussed the importance of stimulating developing countries to participate in the process of vaccine evaluation, not only testing vaccines according to already defined protocols, but also working together with them, in order to take into consideration their local information on virus diversity and host genetic background relevant for the vaccine development and testing, as well as including local virus based reagents to evaluate the immunogenicity of the candidate vaccines.

  13. Understanding ebola virus transmission.

    Science.gov (United States)

    Judson, Seth; Prescott, Joseph; Munster, Vincent

    2015-02-03

    An unprecedented number of Ebola virus infections among healthcare workers and patients have raised questions about our understanding of Ebola virus transmission. Here, we explore different routes of Ebola virus transmission between people, summarizing the known epidemiological and experimental data. From this data, we expose important gaps in Ebola virus research pertinent to outbreak situations. We further propose experiments and methods of data collection that will enable scientists to fill these voids in our knowledge about the transmission of Ebola virus.

  14. Experimental oral and nasal transmission of rabies virus in mice.

    Science.gov (United States)

    Charlton, K M; Casey, G A

    1979-01-01

    Weanling female white Swiss mice were exposed to challenge virus standard rabies virus and street virus isolates from various domestic and wild animals. Virus was given free choice as suspension or as infected mouse brain by stomach tube, by single injection of suspension into the oral cavity of unanesthetized mice, by repeated injection into the oral cavity of anesthetized mice and by single application to the external nares of anesthetized mice. Challenge virus standard virus in mouse brain suspension and a suspension of skunk salivary glands infected with street virus (titers greater than or equal to 10(6)MICLD50/0.03 ml) consistently produced high rates of infection in mice exposed intranasally, low to high rates of infection in mice exposed by forced feeding and other artificial methods of oral exposure and very low rates of infection when given free choice. Street virus isolates passaged intracerebrally in mice had titers less than or equal to 10(4.5) MICLD50/0.03 ml and rarely caused rabies in mice exposed orally or nasally by any method. The results indicate that with the isolates used, virus of high titer (greater than or equal to 10(6)MICLD50/0.03 ml) is required to consistently produce infection in mice by the nasal route and that the mucosa of the nasal cavity probably is the chief route of infection even after oral administration.

  15. Nature and duration of protective immunity to bluetongue virus infection.

    Science.gov (United States)

    Roy, P

    2003-01-01

    Genetic engineering offers a variety of approaches to producing viral vaccines. An exciting advance in this field is the ability to construct virus-like particles (VLPs) that resemble their natural counterparts but lack genetic information. To develop a rationally designed vaccine for bluetongue disease of sheep that is caused by virus (BTV), we have synthesised individual BTV proteins and BTV-like particles (VLPs and CLPs) using baculovirus expression systems and insect cell cultures. A series of clinical trials were undertaken using these proteins and particles in BTV-susceptible sheep. The accumulated data obtained from these studies are: (i) the two surface proteins when used in high doses (approximately 100 microg/dose) could afford complete protection in sheep against virulent virus challenge; (ii) in contrast, only 5-10 microg of VP2 of a related virus, African horse sickness virus (AHSV) afforded protection in horses against virulent virus challenges when vaccinated in the presence of appropriate adjuvant; (iii) vaccination with as little as 10 microg VLPs (consisting of all four major proteins) gave long lasting protection (at least for 14 months) against homologous BTV challenge; (iv) cross-protection was also achieved depending on the challenge virus and amounts of antigen used for vaccination and (v) limited vaccination trials with CLPs (containing only two highly conserved internal proteins) afforded partial (with slight fever) protection against homologous and heterologous virus challenges. Since CLPs are conserved across the twenty four BTV serotypes, CLPs could have potential for a candidate vaccine that may at least mitigate the disease and inhibit virus spread. In summary, VLPs and CLPs offer completely safe and efficacious vaccines as their particles are devoid of any detectable amount of insect, baculovirus proteins or nucleic acids and thus pose no potential adverse effects.

  16. Giant viruses: The difficult breaking of multiple epistemological barriers.

    Science.gov (United States)

    Claverie, Jean-Michel; Abergel, Chantal

    2016-10-01

    The discovery of the first "giant virus", Mimivirus, in 2003 could solely have been that of an exceptional freak, a blind alley of evolution as occasionally encountered in biology, albeit without conceptual significance. On the contrary, once broken this epistemological barrier, additional unrelated families of giant viruses such as the Pandoraviruses, the Pithoviruses and most recently Mollivirus, were quickly unraveled, suggesting that an entire chapter of microbiology had been ignored since Pasteur and Ivanovski. In this article, we examine to what extent the giant viruses challenge previous definitions of viruses, the diversity of forms they could take, and how they might have evolved from extinct ancestral cellular lineages. Inspired by the epistemology of Gaston Bachelard, we will also suggest the reasons for which giant viruses laid hidden in plain sight for more than a century. Finally, we propose a new definition for "viruses" that paradoxically emphasize the fact that they do not encode a single universally shared macromolecule or biochemical function.

  17. Interplay between DNA tumor viruses and the host DNA damage response.

    Science.gov (United States)

    McFadden, Karyn; Luftig, Micah A

    2013-01-01

    Viruses encounter many challenges within host cells in order to replicate their nucleic acid. In the case of DNA viruses, one challenge that must be overcome is recognition of viral DNA structures by the host DNA damage response (DDR) machinery. This is accomplished in elegant and unique ways by different viruses as each has specific needs and sensitivities dependent on its life cycle. In this review, we focus on three DNA tumor viruses and their interactions with the DDR. The viruses Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV) account for nearly all of the virus-associated human cancers worldwide. These viruses have also been excellent models for the study of oncogenic virus-mediated cell transformation. In this review, we will discuss how each of these viruses engage and subvert aspects of the host DDR. The first level of DDR engagement is a result of the genetic linkage between the oncogenic potential of these viruses and their ability to replicate. Namely, the promotion of cells from quiescence into the cell cycle to facilitate virus replication can be sensed through aberrant cellular DNA replication structures which activate the DDR and hinder cell transformation. DNA tumor viruses subvert this growth-suppressive DDR through changes in viral oncoprotein expression which ultimately facilitate virus replication. An additional level of DDR engagement is through direct detection of replicating viral DNA. These interactions parallel those observed in other DNA virus systems in that the need to subvert these intrinsic sensors of aberrant DNA structure in order to replicate must be in place. DNA tumor viruses are no exception. This review will cover the molecular features of DNA tumor virus interactions with the host DDR and the consequences for virus replication.

  18. Interferon-γ Inhibits Ebola Virus Infection.

    Science.gov (United States)

    Rhein, Bethany A; Powers, Linda S; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A; Monick, Martha M; Maury, Wendy

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  19. Interferon-γ Inhibits Ebola Virus Infection.

    Directory of Open Access Journals (Sweden)

    Bethany A Rhein

    Full Text Available Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  20. Viruses infecting reptiles.

    Science.gov (United States)

    Marschang, Rachel E

    2011-11-01

    A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch's postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions.

  1. Classical swine fever (CSF) marker vaccine - Trial I. Challenge studies in weaner pigs

    DEFF Research Database (Denmark)

    Uttenthal, Åse; Le Potier, M.F.; Romero, L.

    2001-01-01

    , -10 or -7, and subsequently challenged at day 0. The challenge virus was CSFV 277, originating from a recent outbreak of classical swine fever (CSF) in Germany. In all groups, only 5 out of 10 pigs were challenged; the remaining 5 pigs served as vaccinated contact controls. Also, three control groups...

  2. Testing for Human Immunodeficiency Virus

    Science.gov (United States)

    ... education Fact Sheet PFS005: Testing for Human Immunodeficiency Virus AUGUST 2015 • Reasons for Getting Tested • Who Should ... For More Information • Glossary Testing for Human Immunodeficiency Virus Human immunodeficiency virus (HIV) is the virus that ...

  3. Thank You, Challenges!

    Institute of Scientific and Technical Information of China (English)

    陈晨; 陈传光

    2016-01-01

    A person may meet many challenges in his or her life.Some people think challenges are terrible.But I think they’re great.And I want to say,"Thank you,challenges!"For some people,it’s hard to face the challenges because they are afraid of failing in the end.However,it’s necessary for a person to face the challenges.Challenges are good to~①you.

  4. Viruses in the sea

    Science.gov (United States)

    Suttle, Curtis A.

    2005-09-01

    Viruses exist wherever life is found. They are a major cause of mortality, a driver of global geochemical cycles and a reservoir of the greatest genetic diversity on Earth. In the oceans, viruses probably infect all living things, from bacteria to whales. They affect the form of available nutrients and the termination of algal blooms. Viruses can move between marine and terrestrial reservoirs, raising the spectre of emerging pathogens. Our understanding of the effect of viruses on global systems and processes continues to unfold, overthrowing the idea that viruses and virus-mediated processes are sidebars to global processes.

  5. An Intranasal Virus-Like Particle Vaccine Broadly Protects Mice from Multiple Subtypes of Influenza A Virus.

    Science.gov (United States)

    Schwartzman, Louis M; Cathcart, Andrea L; Pujanauski, Lindsey M; Qi, Li; Kash, John C; Taubenberger, Jeffery K

    2015-07-21

    Influenza virus infections are a global public health problem, with a significant impact of morbidity and mortality from both annual epidemics and pandemics. The current strategy for preventing annual influenza is to develop a new vaccine each year against specific circulating virus strains. Because these vaccines are unlikely to protect against an antigenically divergent strain or a new pandemic virus with a novel hemagglutinin (HA) subtype, there is a critical need for vaccines that protect against all influenza A viruses, a so-called "universal" vaccine. Here we show that mice were broadly protected against challenge with a wide variety of lethal influenza A virus infections (94% aggregate survival following vaccination) with a virus-like particle (VLP) vaccine cocktail. The vaccine consisted of a mixture of VLPs individually displaying H1, H3, H5, or H7 HAs, and vaccinated mice showed significant protection following challenge with influenza viruses expressing 1918 H1, 1957 H2, and avian H5, H6, H7, H10, and H11 hemagglutinin subtypes. These experiments suggest a promising and practical strategy for developing a broadly protective "universal" influenza vaccine. The rapid and unpredictable nature of influenza A virus evolution requires new vaccines to be produced annually to match circulating strains. Human infections with influenza viruses derived from animals can cause outbreaks that may be associated with high mortality, and such strains may also adapt to humans to cause a future pandemic. Thus, there is a large public health need to create broadly protective, or "universal," influenza vaccines that could prevent disease from a wide variety of human and animal influenza A viruses. In this study, a noninfectious virus-like particle (VLP) vaccine was shown to offer significant protection against a variety of influenza A viruses in mice, suggesting a practical strategy to develop a universal influenza vaccine. Copyright © 2015 Schwartzman et al.

  6. Immune Efficacy of a Recombinant Fowlpox Virus Co-Ex-pressing HA and NA Genes of Avian Influenza Virus in SPF Chickens

    Institute of Scientific and Technical Information of China (English)

    QIAO Chuan-ling; JIANG Yong-ping; YU Kang-zhen; TIAN Guo-bin; CHEN Hua-lan

    2004-01-01

    A recombinant fowlpox virus co-expressing Haemagglutinin(HA)and Neuraminidase(NA)named as rFPV-HA-NA was produced by HA and NA gene of A/Goose/Guangdong/3/96(H5N1)isolate of avian influenza virus recombined into the genome of fowlpox virus. In this study,to evaluate its ability of protecting chickens against challenge with a lethal dose of highly pathogenic isolates of avian influenza virus,eight-week-old specificpathogenic-free(SPF)chickens were vaccinated with recombinant virus or the wildtypefowlpox virus by wing-web puncture. After challenge 4 weeks with 10 LD50 highly pathogenic avian influenza virus H5N1 and H7N1 isolate,all chickens vaccinated with recombinant virus were protected,while the chickens vaccinated with the wildtype fowlpox virus or unvaccinated controls experienced 100% mortality respectively following challenge. This complete protection was accompanied by the high levels of specific antibody response to the respectivecomponents of the recombinant virus.

  7. Chimeric yellow fever/dengue virus as a candidate dengue vaccine: quantitation of the dengue virus-specific CD8 T-cell response.

    Science.gov (United States)

    van Der Most, R G; Murali-Krishna, K; Ahmed, R; Strauss, J H

    2000-09-01

    We have constructed a chimeric yellow fever/dengue (YF/DEN) virus, which expresses the premembrane (prM) and envelope (E) genes from DEN type 2 (DEN-2) virus in a YF virus (YFV-17D) genetic background. Immunization of BALB/c mice with this chimeric virus induced a CD8 T-cell response specific for the DEN-2 virus prM and E proteins. This response protected YF/DEN virus-immunized mice against lethal dengue encephalitis. Control mice immunized with the parental YFV-17D were not protected against DEN-2 virus challenge, indicating that protection was mediated by the DEN-2 virus prM- and E-specific immune responses. YF/DEN vaccine-primed CD8 T cells expanded and were efficiently recruited into the central nervous systems of DEN-2 virus challenged mice. At 5 days after challenge, 3 to 4% of CD8 T cells in the spleen were specific for the prM and E proteins, and 34% of CD8 T cells in the central nervous system recognized these proteins. Depletion of either CD4 or CD8 T cells, or both, strongly reduced the protective efficacy of the YF/DEN virus, stressing the key role of the antiviral T-cell response.

  8. Hepatitis Delta Virus: A Peculiar Virus

    OpenAIRE

    Carolina Alves; Cristina Branco; Celso Cunha

    2013-01-01

    The hepatitis delta virus (HDV) is distributed worldwide and related to the most severe form of viral hepatitis. HDV is a satellite RNA virus dependent on hepatitis B surface antigens to assemble its envelope and thus form new virions and propagate infection. HDV has a small 1.7 Kb genome making it the smallest known human virus. This deceivingly simple virus has unique biological features and many aspects of its life cycle remain elusive. The present review endeavors to gather the available ...

  9. Etiology and immunology of infectious bronchitis virus

    Directory of Open Access Journals (Sweden)

    LF Caron

    2010-06-01

    Full Text Available Infectious bronchitis virus (IBV of chickens is currently one of the main diseases associated with respiratory syndrome in domestic poultry, as well as with losses related to egg production. The etiological agent is a coronavirus, which presents structural differences in the field, mainly in the S1 spike protein. The immune response against this virus is complicated by the few similarities among serotypes. Environmental and management factors, as well as the high mutation rate of the virus, render it difficult to control the disease and compromise the efficacy of the available vaccines. Bird immune system capacity to respond to challenges depend on the integrity of the mucosae, as an innate compartment, and on the generation of humoral and cell-mediated adaptive responses, and may affect the health status of breeding stocks in the medium run. Vaccination of day-old chicks in the hatchery on aims at eliciting immune responses, particularly cell-mediated responses that are essential when birds are first challenged. Humoral response (IgY and IgA are also important for virus clearance in subsequent challenges. The presence of antibodies against the S1 spike protein in 3- to 4-week-old birds is important both in broilers and for immunological memory in layers and breeders.

  10. Protection against Marek's disease by a fowlpox virus recombinant expressing the glycoprotein B of Marek's disease virus.

    Science.gov (United States)

    Nazerian, K; Lee, L F; Yanagida, N; Ogawa, R

    1992-03-01

    Fowlpox virus (FPV) recombinants expressing the glycoprotein B and the phosphorylated protein (pp38) of the GA strain of Marek's disease virus (MDV) were assayed for their ability to protect chickens against challenge with virulent MDV. The recombinant FPV expressing the glycoprotein B gene elicited neutralizing antibodies against MDV, significantly reduced the level of cell-associated viremia, and, similar to the conventional herpesvirus of turkeys, protected chickens against challenge with the GA strain and the highly virulent RB1B and Md5 strains of MDV. The recombinant FPV expressing the pp38 gene failed to either elicit neutralizing antibodies against MDV or protect the vaccinated chickens against challenge with MDV.

  11. Virus Infection

    Directory of Open Access Journals (Sweden)

    Hiroshi Abe

    2013-01-01

    Full Text Available Of 168 patients with chronic hepatitis B virus (HBV infection-related liver disease, 20 patients who had received 100 mg of lamivudine plus 10 mg/day of adefovir dipivoxil (ADV (ADV group and 124 patients who had received 0.5 mg/day of entecavir or 100 mg/day of lamivudine (non-ADV group for >1 year were enrolled. For comparative analyses, 19 well-matched pairs were obtained from the groups by propensity scores. At the time of enrollment, serum creatinine and phosphate concentrations were similar between the ADV and non-ADV groups; however, urinary phosphate ( and serum bone-specific alkaline phosphatase (BAP ( concentrations were significantly higher in the ADV group than in the non-ADV group. Serum BAP was significantly higher at the time of enrollment than before ADV administration in the ADV group (, although there was no significant change in serum BAP concentration in the non-ADV group. There was a significant positive correlation between the period of ADV therapy and ΔBAP (, . Serum BAP concentration increased before increase in serum creatinine concentration and was useful for early detection of adverse events and for developing adequate measures for continuing ADV for chronic HBV infection-related liver disease.

  12. Role of viruses and bacteria-virus interactions in autoimmunity.

    Science.gov (United States)

    Steed, Ashley L; Stappenbeck, Thaddeus S

    2014-12-01

    A potential role for viral and bacterial-viral interactions in the pathogenesis of autoimmune disease has been long recognized. Recently, intensive investigation has begun to decipher interactions between specific microbes with the host that contribute toward autoimmunity. This work has primarily focused on known viral and bacterial pathogens. A major challenge is to determine the role of bacteria that are typically considered as commensals as well as chronic viruses. Furthermore, equally challenging is to prove causality given the potential complexity of microbe-microbe interactions. Important initial contributions to this field have shown that specific interactions of microbes with hosts that contain a background of genetic susceptibility can play a role in autoimmune pathogenesis. In this review, we describe principles of immune tolerance with a focus on its breakdown during pathogenic as well as commensal relationships between the host and the microbial world.

  13. Durability of a vesicular stomatitis virus-based marburg virus vaccine in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Chad E Mire

    Full Text Available The filoviruses, Marburg virus (MARV and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV that expresses individual filovirus glycoproteins (GPs in place of the VSV glycoprotein (G. These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28-35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines.

  14. Durability of a vesicular stomatitis virus-based marburg virus vaccine in nonhuman primates.

    Science.gov (United States)

    Mire, Chad E; Geisbert, Joan B; Agans, Krystle N; Satterfield, Benjamin A; Versteeg, Krista M; Fritz, Elizabeth A; Feldmann, Heinz; Hensley, Lisa E; Geisbert, Thomas W

    2014-01-01

    The filoviruses, Marburg virus (MARV) and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV) that expresses individual filovirus glycoproteins (GPs) in place of the VSV glycoprotein (G). These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28-35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines.

  15. The Strange Lifestyle of Multipartite Viruses.

    Directory of Open Access Journals (Sweden)

    Anne Sicard

    2016-11-01

    Full Text Available Multipartite viruses have one of the most puzzling genetic organizations found in living organisms. These viruses have several genome segments, each containing only a part of the genetic information, and each individually encapsidated into a separate virus particle. While countless studies on molecular and cellular mechanisms of the infection cycle of multipartite viruses are available, just as for other virus types, very seldom is their lifestyle questioned at the viral system level. Moreover, the rare available "system" studies are purely theoretical, and their predictions on the putative benefit/cost balance of this peculiar genetic organization have not received experimental support. In light of ongoing progresses in general virology, we here challenge the current hypotheses explaining the evolutionary success of multipartite viruses and emphasize their shortcomings. We also discuss alternative ideas and research avenues to be explored in the future in order to solve the long-standing mystery of how viral systems composed of interdependent but physically separated information units can actually be functional.

  16. Acute paralysis viruses of the honey bee

    Institute of Scientific and Technical Information of China (English)

    Chunsheng; Hou; Nor; Chejanovsky

    2014-01-01

    <正>The alarming decline of honey bee(Apis mellifera)colonies in the last decade drove the attention and research to several pathogens of the honey bee including viruses.Viruses challenge the development of healthy and robust colonies since they manage to prevail in an asymptomatic mode and reemerge in acute infections following external stresses,as well as they are able to infect new healthy colonies(de Miranda J R,et al.,2010a;de Miranda J R,et al.,2010b;Di Prisco G,et al.,2013;Nazzi F,et al.,2012;Yang X L,et al.,2005).

  17. Avirulent Avian Influenza Virus as a Vaccine Strain against a Potential Human Pandemic

    Science.gov (United States)

    Takada, Ayato; Kuboki, Noritaka; Okazaki, Katsunori; Ninomiya, Ai; Tanaka, Hiroko; Ozaki, Hiroichi; Itamura, Shigeyuki; Nishimura, Hidekazu; Enami, Masayoshi; Tashiro, Masato; Shortridge, Kennedy F.; Kida, Hiroshi

    1999-01-01

    In the influenza H5N1 virus incident in Hong Kong in 1997, viruses that are closely related to H5N1 viruses initially isolated in a severe outbreak of avian influenza in chickens were isolated from humans, signaling the possibility of an incipient pandemic. However, it was not possible to prepare a vaccine against the virus in the conventional embryonated egg system because of the lethality of the virus for chicken embryos and the high level of biosafety therefore required for vaccine production. Alternative approaches, including an avirulent H5N4 virus isolated from a migratory duck as a surrogate virus, H5N1 virus as a reassortant with avian virus H3N1 and an avirulent recombinant H5N1 virus generated by reverse genetics, have been explored. All vaccines were formalin inactivated. Intraperitoneal immunization of mice with each of vaccines elicited the production of hemagglutination-inhibiting and virus-neutralizing antibodies, while intranasal vaccination without adjuvant induced both mucosal and systemic antibody responses that protected the mice from lethal H5N1 virus challenge. Surveillance of birds and animals, particularly aquatic birds, for viruses to provide vaccine strains, especially surrogate viruses, for a future pandemic is stressed. PMID:10482580

  18. Acute bee paralysis virus [

    Lifescience Database Archive (English)

    Full Text Available Acute bee paralysis virus [gbvrl]: 14 CDS's (15780 codons) fields: [triplet