Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine

Elizabeth A. Poore, Dawn K. Slifka, Hans Peter Raué, Archana Thomas, Erika Hammarlund, Benjamin K. Quintel, Lindsay L. Torrey, Ariel M. Slifka, Justin M. Richner, Melissa E. Dubois, Lawrence P. Johnson, Michael S. Diamond, Mark Slifka, Ian J. Amanna

    Research output: Contribution to journalArticle

    9 Scopus citations

    Abstract

    West Nile virus (WNV) is a mosquito-transmitted pathogen with a wide geographical range that can lead to long-term disability and death in some cases. Despite the public health risk posed by WNV, including an estimated 3 million infections in the United States alone, no vaccine is available for use in humans. Here, we present a scaled manufacturing approach for production of a hydrogen peroxide-inactivated whole virion WNV vaccine, termed HydroVax-001 WNV. Vaccination resulted in robust virus-specific neutralizing antibody responses and protection against WNV-associated mortality in mice or viremia in rhesus macaques (RM). A GLP-compliant toxicology study performed in rats demonstrated an excellent safety profile with clinical findings limited to minor and transient irritation at the injection site. An in vitro relative potency (IVRP) assay was developed and shown to correlate with in vivo responses following forced degradation studies. Long-term in vivo potency comparisons between the intended storage condition (2–8 °C) and a thermally stressed condition (40 ± 2 °C) demonstrated no loss in vaccine efficacy or protective immunity over a 6-month span of time. Together, the positive pre-clinical findings regarding immunogenicity, safety, and stability indicate that HydroVax-001 WNV is a promising vaccine candidate.

    Original languageEnglish (US)
    Pages (from-to)283-292
    Number of pages10
    JournalVaccine
    Volume35
    Issue number2
    DOIs
    StatePublished - Jan 5 2017

    Keywords

    • Antibody
    • Hydrogen peroxide
    • Rhesus macaque
    • Vaccination
    • Vaccine
    • West Nile virus

    ASJC Scopus subject areas

    • Molecular Medicine
    • Immunology and Microbiology(all)
    • veterinary(all)
    • Public Health, Environmental and Occupational Health
    • Infectious Diseases

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  • Cite this

    Poore, E. A., Slifka, D. K., Raué, H. P., Thomas, A., Hammarlund, E., Quintel, B. K., Torrey, L. L., Slifka, A. M., Richner, J. M., Dubois, M. E., Johnson, L. P., Diamond, M. S., Slifka, M., & Amanna, I. J. (2017). Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine. Vaccine, 35(2), 283-292. https://doi.org/10.1016/j.vaccine.2016.11.080