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Biological Attack

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KELLY LYN WARFIELD – 1st expert on this subject based on the ideXlab platform

  • Vaccine to confer to nonhuman primates complete protection against multistrain Ebola and Marburg virus infections
    Clinical and Vaccine Immunology, 2008
    Co-Authors: Dana L Swenson, KELLY LYN WARFIELD, Danher Wang, Min Luo, Jan Woraratanadharm, David H Holman, John Y. Dong, William D. Pratt

    Abstract:

    Filoviruses (Ebola and Marburg viruses) are among the deadliest viruses known to mankind, with mortality rates nearing 90%. These pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. Additionally, there are currently no licensed vaccines available to prevent filovirus outbreaks. Their high mortality rates and infectious capabilities when aerosolized and the lack of licensed vaccines available to prevent such infectious make Ebola and Marburg viruses serious bioterrorism threats, placing them both on the category A list of bioterrorism agents. Here we describe a panfilovirus vaccine based on a complex adenovirus (CAdVax) technology that expresses multiple antigens from five different filoviruses de novo. Vaccination of nonhuman primates demonstrated 100% protection against infection by two species of Ebola virus and three Marburg virus subtypes, each administered at 1,000 times the lethal dose. This study indicates the feasibility of vaccination against all current filovirus threats in the event of natural hemorrhagic fever outbreak or Biological Attack.

  • Ebola virus-like particles protect from lethal Ebola virus infection.
    Proceedings of the National Academy of Sciences of the United States of America, 2003
    Co-Authors: KELLY LYN WARFIELD, Catharine M. Bosio, Brent C Welcher, Emily M Deal, Mansour Mohamadzadeh, A Schmaljohn, M. Javad Aman, Sina Bavari

    Abstract:

    The filovirus Ebola causes hemorrhagic fever with 70-80% human mortality. High case-fatality rates, as well as known aerosol infectivity, make Ebola virus a potential global health threat and possible Biological warfare agent. Development of an effective vaccine for use in natural outbreaks, response to Biological Attack, and protection of laboratory workers is a higher national priority than ever before. Coexpression of the Ebola virus glycoprotein (GP) and matrix protein (VP40) in mammalian cells results in spontaneous production and release of virus-like particles (VLPs) that resemble the distinctively filamentous infectious virions. VLPs have been tested and found efficacious as vaccines for several viruses, including papillomavirus, HIV, parvovirus, and rotavirus. Herein, we report that Ebola VLPs (eVLPs) were immunogenic in vitro as eVLPs matured and activated mouse bone marrow-derived dendritic cells, assessed by increases in cell-surface markers CD40, CD80, CD86, and MHC class I and II and secretion of IL-6, IL-10, macrophage inflammatory protein (MIP)-1alpha, and tumor necrosis factor alpha by the dendritic cells. Further, vaccinating mice with eVLPs activated CD4+ and CD8+ T cells, as well as CD19+ B cells. After vaccination with eVLPs, mice developed high titers of Ebola virus-specific antibodies, including neutralizing antibodies. Importantly, mice vaccinated with eVLPs were 100% protected from an otherwise lethal Ebola virus inoculation. Together, our data suggest that eVLPs represent a promising vaccine candidate for protection against Ebola virus infections and a much needed tool to examine the genesis and nature of immune responses to Ebola virus.

William D. Pratt – 2nd expert on this subject based on the ideXlab platform

  • Vaccine to confer to nonhuman primates complete protection against multistrain Ebola and Marburg virus infections
    Clinical and Vaccine Immunology, 2008
    Co-Authors: Dana L Swenson, KELLY LYN WARFIELD, Danher Wang, Min Luo, Jan Woraratanadharm, David H Holman, John Y. Dong, William D. Pratt

    Abstract:

    Filoviruses (Ebola and Marburg viruses) are among the deadliest viruses known to mankind, with mortality rates nearing 90%. These pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. Additionally, there are currently no licensed vaccines available to prevent filovirus outbreaks. Their high mortality rates and infectious capabilities when aerosolized and the lack of licensed vaccines available to prevent such infectious make Ebola and Marburg viruses serious bioterrorism threats, placing them both on the category A list of bioterrorism agents. Here we describe a panfilovirus vaccine based on a complex adenovirus (CAdVax) technology that expresses multiple antigens from five different filoviruses de novo. Vaccination of nonhuman primates demonstrated 100% protection against infection by two species of Ebola virus and three Marburg virus subtypes, each administered at 1,000 times the lethal dose. This study indicates the feasibility of vaccination against all current filovirus threats in the event of natural hemorrhagic fever outbreak or Biological Attack.

Sina Bavari – 3rd expert on this subject based on the ideXlab platform

  • Ebola virus-like particles protect from lethal Ebola virus infection.
    Proceedings of the National Academy of Sciences of the United States of America, 2003
    Co-Authors: KELLY LYN WARFIELD, Catharine M. Bosio, Brent C Welcher, Emily M Deal, Mansour Mohamadzadeh, A Schmaljohn, M. Javad Aman, Sina Bavari

    Abstract:

    The filovirus Ebola causes hemorrhagic fever with 70-80% human mortality. High case-fatality rates, as well as known aerosol infectivity, make Ebola virus a potential global health threat and possible Biological warfare agent. Development of an effective vaccine for use in natural outbreaks, response to Biological Attack, and protection of laboratory workers is a higher national priority than ever before. Coexpression of the Ebola virus glycoprotein (GP) and matrix protein (VP40) in mammalian cells results in spontaneous production and release of virus-like particles (VLPs) that resemble the distinctively filamentous infectious virions. VLPs have been tested and found efficacious as vaccines for several viruses, including papillomavirus, HIV, parvovirus, and rotavirus. Herein, we report that Ebola VLPs (eVLPs) were immunogenic in vitro as eVLPs matured and activated mouse bone marrow-derived dendritic cells, assessed by increases in cell-surface markers CD40, CD80, CD86, and MHC class I and II and secretion of IL-6, IL-10, macrophage inflammatory protein (MIP)-1alpha, and tumor necrosis factor alpha by the dendritic cells. Further, vaccinating mice with eVLPs activated CD4+ and CD8+ T cells, as well as CD19+ B cells. After vaccination with eVLPs, mice developed high titers of Ebola virus-specific antibodies, including neutralizing antibodies. Importantly, mice vaccinated with eVLPs were 100% protected from an otherwise lethal Ebola virus inoculation. Together, our data suggest that eVLPs represent a promising vaccine candidate for protection against Ebola virus infections and a much needed tool to examine the genesis and nature of immune responses to Ebola virus.