Protective antibodies against Eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 glycoprotein

Arthur S. Kim, S. Kyle Austin, Christina L. Gardner, Adam Zuiani, Douglas S. Reed, Derek W. Trobaugh, Chengqun Sun, Katherine Basore, Lauren E. Williamson, James E. Crowe, Mark K. Slifka, Daved H. Fremont, William B. Klimstra, Michael S. Diamond

    Research output: Contribution to journalArticle

    5 Scopus citations

    Abstract

    Eastern equine encephalitis virus (EEEV) is a mosquito-transmitted alphavirus with a high case mortality rate in humans. EEEV is a biodefence concern because of its potential for aerosol spread and the lack of existing countermeasures. Here, we identify a panel of 18 neutralizing murine monoclonal antibodies (mAbs) against the EEEV E2 glycoprotein, several of which have ‘elite’ activity with 50 and 99% effective inhibitory concentrations (EC50 and EC99) of less than 10 and 100 ng ml−1, respectively. Alanine-scanning mutagenesis and neutralization escape mapping analysis revealed epitopes for these mAbs in domains A or B of the E2 glycoprotein. A majority of the neutralizing mAbs blocked infection at a post-attachment stage, with several inhibiting viral membrane fusion. Administration of one dose of anti-EEEV mAb protected mice from lethal subcutaneous or aerosol challenge. These experiments define the mechanistic basis for neutralization by protective anti-EEEV mAbs and suggest a path forward for treatment and vaccine design.

    Original languageEnglish (US)
    Pages (from-to)187-197
    Number of pages11
    JournalNature Microbiology
    Volume4
    Issue number1
    DOIs
    StatePublished - Jan 1 2019

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Applied Microbiology and Biotechnology
    • Genetics
    • Microbiology (medical)
    • Cell Biology

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  • Cite this

    Kim, A. S., Austin, S. K., Gardner, C. L., Zuiani, A., Reed, D. S., Trobaugh, D. W., Sun, C., Basore, K., Williamson, L. E., Crowe, J. E., Slifka, M. K., Fremont, D. H., Klimstra, W. B., & Diamond, M. S. (2019). Protective antibodies against Eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 glycoprotein. Nature Microbiology, 4(1), 187-197. https://doi.org/10.1038/s41564-018-0286-4