Virus Hemorrhagic Fever

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Joan B Geisbert - One of the best experts on this subject based on the ideXlab platform.

  • interferon β therapy prolongs survival in rhesus macaque models of ebola and marburg Hemorrhagic Fever
    The Journal of Infectious Diseases, 2013
    Co-Authors: Lauren M Smith, Lisa E. Hensley, Thomas W Geisbert, Joan B Geisbert, Joshua C Johnson, Andrea Stossel, Anna N Honko, Judy Y Yen
    Abstract:

    There is a clear need for novel, effective therapeutic approaches to Hemorrhagic Fever due to filoViruses. Ebola Virus Hemorrhagic Fever is associated with robust interferon (IFN)–α production, with plasma concentrations of IFN-α that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN-β production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-β therapy in filoVirus infection. Here we show that early postexposure treatment with IFN-β significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola Virus, although it failed to alter mortality. Early treatment with IFN-β also significantly increased survival time after Marburg Virus infection. IFN-β may have promise as an adjunctive postexposure therapy in filoVirus infection.

Steven M Jones - One of the best experts on this subject based on the ideXlab platform.

  • assessment of a vesicular stomatitis Virus based vaccine by use of the mouse model of ebola Virus Hemorrhagic Fever
    The Journal of Infectious Diseases, 2007
    Co-Authors: Steven M Jones, Ute Stroher, Lisa Fernando, Xianggou Qiu, Judie B Alimonti, Pasquale Melito, Mike Bray, Hansdieter Klenk
    Abstract:

    Background. In humans and nonhuman primates, Ebola Virus causes a virulent viral Hemorrhagic Fever for which no licensed vaccines or therapeutic drugs exist. In the present study, we used the mouse model for Ebola Hemorrhagic Fever to assess the safety and efficacy of a vaccine based on a live attenuated vesicular stomatitis Virus expressing the Zaire ebolaVirus (ZEBOV) glycoprotein. Methods. Healthy mice were given the vaccine in various doses, decreasing from 2 X 10 4 to 2 plaque-forming units (pfu), with both systemic and mucosal vaccination routes used. Mice were challenged with 10 3 to 10 6 lethal doses of mouse-adapted ZEBOV. Severely immunocompromised mice were injected with 2 X 10 5 pfu, which is 10 times greater than the immunization dose normally used, to test vaccine safety. Results. Two plaque-forming units of the vaccine protected against lethal challenge, and mucosal immunization was found to be as protective as systemic injection. The replicating vaccine was never detected in the immunized animals, nor were there clinical signs after immunization. Immunization of severely immunocompromised mice with 200,000 pfu of vaccine resulted in no clinical symptoms. Conclusions. Our data suggest that the vaccine is highly potent and safe and that it very rapidly induces "sterile" immunity in mice. The potential for mucosal delivery, if confirmed in nonhuman primates, makes it an excellent candidate for mass immunization during outbreaks or in the event of intentional release.

Hansdieter Klenk - One of the best experts on this subject based on the ideXlab platform.

  • assessment of a vesicular stomatitis Virus based vaccine by use of the mouse model of ebola Virus Hemorrhagic Fever
    The Journal of Infectious Diseases, 2007
    Co-Authors: Steven M Jones, Ute Stroher, Lisa Fernando, Xianggou Qiu, Judie B Alimonti, Pasquale Melito, Mike Bray, Hansdieter Klenk
    Abstract:

    Background. In humans and nonhuman primates, Ebola Virus causes a virulent viral Hemorrhagic Fever for which no licensed vaccines or therapeutic drugs exist. In the present study, we used the mouse model for Ebola Hemorrhagic Fever to assess the safety and efficacy of a vaccine based on a live attenuated vesicular stomatitis Virus expressing the Zaire ebolaVirus (ZEBOV) glycoprotein. Methods. Healthy mice were given the vaccine in various doses, decreasing from 2 X 10 4 to 2 plaque-forming units (pfu), with both systemic and mucosal vaccination routes used. Mice were challenged with 10 3 to 10 6 lethal doses of mouse-adapted ZEBOV. Severely immunocompromised mice were injected with 2 X 10 5 pfu, which is 10 times greater than the immunization dose normally used, to test vaccine safety. Results. Two plaque-forming units of the vaccine protected against lethal challenge, and mucosal immunization was found to be as protective as systemic injection. The replicating vaccine was never detected in the immunized animals, nor were there clinical signs after immunization. Immunization of severely immunocompromised mice with 200,000 pfu of vaccine resulted in no clinical symptoms. Conclusions. Our data suggest that the vaccine is highly potent and safe and that it very rapidly induces "sterile" immunity in mice. The potential for mucosal delivery, if confirmed in nonhuman primates, makes it an excellent candidate for mass immunization during outbreaks or in the event of intentional release.

Ute Stroher - One of the best experts on this subject based on the ideXlab platform.

  • assessment of a vesicular stomatitis Virus based vaccine by use of the mouse model of ebola Virus Hemorrhagic Fever
    The Journal of Infectious Diseases, 2007
    Co-Authors: Steven M Jones, Ute Stroher, Lisa Fernando, Xianggou Qiu, Judie B Alimonti, Pasquale Melito, Mike Bray, Hansdieter Klenk
    Abstract:

    Background. In humans and nonhuman primates, Ebola Virus causes a virulent viral Hemorrhagic Fever for which no licensed vaccines or therapeutic drugs exist. In the present study, we used the mouse model for Ebola Hemorrhagic Fever to assess the safety and efficacy of a vaccine based on a live attenuated vesicular stomatitis Virus expressing the Zaire ebolaVirus (ZEBOV) glycoprotein. Methods. Healthy mice were given the vaccine in various doses, decreasing from 2 X 10 4 to 2 plaque-forming units (pfu), with both systemic and mucosal vaccination routes used. Mice were challenged with 10 3 to 10 6 lethal doses of mouse-adapted ZEBOV. Severely immunocompromised mice were injected with 2 X 10 5 pfu, which is 10 times greater than the immunization dose normally used, to test vaccine safety. Results. Two plaque-forming units of the vaccine protected against lethal challenge, and mucosal immunization was found to be as protective as systemic injection. The replicating vaccine was never detected in the immunized animals, nor were there clinical signs after immunization. Immunization of severely immunocompromised mice with 200,000 pfu of vaccine resulted in no clinical symptoms. Conclusions. Our data suggest that the vaccine is highly potent and safe and that it very rapidly induces "sterile" immunity in mice. The potential for mucosal delivery, if confirmed in nonhuman primates, makes it an excellent candidate for mass immunization during outbreaks or in the event of intentional release.

Lisa E. Hensley - One of the best experts on this subject based on the ideXlab platform.

  • interferon β therapy prolongs survival in rhesus macaque models of ebola and marburg Hemorrhagic Fever
    The Journal of Infectious Diseases, 2013
    Co-Authors: Lauren M Smith, Lisa E. Hensley, Thomas W Geisbert, Joan B Geisbert, Joshua C Johnson, Andrea Stossel, Anna N Honko, Judy Y Yen
    Abstract:

    There is a clear need for novel, effective therapeutic approaches to Hemorrhagic Fever due to filoViruses. Ebola Virus Hemorrhagic Fever is associated with robust interferon (IFN)–α production, with plasma concentrations of IFN-α that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN-β production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-β therapy in filoVirus infection. Here we show that early postexposure treatment with IFN-β significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola Virus, although it failed to alter mortality. Early treatment with IFN-β also significantly increased survival time after Marburg Virus infection. IFN-β may have promise as an adjunctive postexposure therapy in filoVirus infection.