Advanced oxidation technology for the development of a next-generation inactivated West Nile virus vaccine

Benjamin K. Quintel, Archana Thomas, Danae E. Poer DeRaad, Mark Slifka, Ian J. Amanna

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    West Nile virus (WNV) is the most frequent mosquito-borne disease reported in the continental United States and although an effective veterinary vaccine exists for horses, there is still no commercial vaccine approved for human use. We have previously tested a 3% hydrogen peroxide (H2O2)-based WNV inactivation approach termed, HydroVax, in Phase I clinical trials and the vaccine was found to be safe and modestly immunogenic. Here, we describe an advanced, next-generation oxidation approach (HydroVax-II) for the development of inactivated vaccines that utilizes reduced concentrations of H2O2 in combination with copper (cupric ions, Cu2+) complexed with the antiviral compound, methisazone (MZ). Further enhancement of this oxidative approach included the addition of a low percentage of formaldehyde, a cross-linking reagent with a different mechanism of action that, together with H2O2/Cu/MZ, provides a robust two-pronged approach to virus inactivation. Together, this new approach results in rapid virus inactivation while greatly improving the maintenance of WNV-specific neutralizing epitopes mapped across the three structural domains of the WNV envelope protein. In combination with more refined manufacturing techniques, this inactivation technology resulted in vaccine-mediated WNV-specific neutralizing antibody responses that were 130-fold higher than that observed using the first generation, H2O2-only vaccine approach and provided 100% protection against lethal WNV infection. This new approach to vaccine development represents an important area for future investigation with the potential not only for improving vaccines against WNV, but other clinically relevant viruses as well.

    Original languageEnglish (US)
    JournalVaccine
    DOIs
    StateAccepted/In press - Jan 1 2019

    Fingerprint

    West Nile Virus Vaccines
    West Nile virus
    Inactivated Vaccines
    Virus Inactivation
    Vaccines
    Methisazone
    oxidation
    vaccines
    Technology
    inactivation
    Cross-Linking Reagents
    Viral Envelope Proteins
    viruses
    Clinical Trials, Phase I
    Virus Diseases
    mosquito-borne diseases
    Neutralizing Antibodies
    Culicidae
    Hydrogen Peroxide
    Formaldehyde

    Keywords

    • Advanced oxidation
    • Antibody
    • Hydrogen peroxide
    • 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

    Cite this

    Advanced oxidation technology for the development of a next-generation inactivated West Nile virus vaccine. / Quintel, Benjamin K.; Thomas, Archana; Poer DeRaad, Danae E.; Slifka, Mark; Amanna, Ian J.

    In: Vaccine, 01.01.2019.

    Research output: Contribution to journalArticle

    Quintel, Benjamin K. ; Thomas, Archana ; Poer DeRaad, Danae E. ; Slifka, Mark ; Amanna, Ian J. / Advanced oxidation technology for the development of a next-generation inactivated West Nile virus vaccine. In: Vaccine. 2019.
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