Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections

Iuliia Gilchuk, Pavlo Gilchuk, Gopal Sapparapu, Rebecca Lampley, Vidisha Singh, Nurgun Kose, David L. Blum, Laura J. Hughes, Panayampalli S. Satheshkumar, Michael B. Townsend, Ashley V. Kondas, Zachary Reed, Zachary Weiner, Victoria A. Olson, Erika Hammarlund, Hans Peter Raue, Mark Slifka, James C. Slaughter, Barney S. Graham, Kathryn M. EdwardsRoselyn J. Eisenberg, Gary H. Cohen, Sebastian Joyce, James E. Crowe

    Research output: Contribution to journalArticle

    16 Scopus citations

    Abstract

    Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, CPXV, MPXV, and VARV and that are determinants of protection in murine challenge models. Optimal protection following respiratory or systemic infection required a mixture of Abs that targeted several membrane proteins, including proteins on enveloped and mature virion forms of virus. This work reveals orthopoxvirus targets for human Abs that mediate cross-protective immunity and identifies new candidate Ab therapeutic mixtures to replace VIG.

    Original languageEnglish (US)
    Pages (from-to)684-694.e9
    JournalCell
    Volume167
    Issue number3
    DOIs
    Publication statusPublished - Oct 20 2016

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    Keywords

    • antigen specificity
    • cross-neutralization
    • human monoclonal antibodies
    • poxvirus infections
    • protective immunity
    • smallpox vaccine

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

    Cite this

    Gilchuk, I., Gilchuk, P., Sapparapu, G., Lampley, R., Singh, V., Kose, N., ... Crowe, J. E. (2016). Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections. Cell, 167(3), 684-694.e9. https://doi.org/10.1016/j.cell.2016.09.049