A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge

Amarendra Pegu, Bhavesh Borate, Yunda Huang, Matthias G. Pauthner, Ann J. Hessell, Boris Julg, Nicole A. Doria-Rose, Stephen D. Schmidt, Lindsay N. Carpp, Michelle D. Cully, Xuejun Chen, George M. Shaw, Dan H. Barouch, Nancy L. Haigwood, Lawrence Corey, Dennis R. Burton, Mario Roederer, Peter B. Gilbert, John R. Mascola, Ying Huang

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    2 Scopus citations

    Abstract

    Passively administered broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) have been shown to protect non-human primates (NHPs) against chimeric simian-human immunodeficiency virus (SHIV) infection. With data from multiple non-human primate SHIV challenge studies that used single bNAbs, we conducted a meta-analysis to examine the relationship between predicted serum 50% neutralization titer (ID50) against the challenge virus and infection outcome. In a logistic model that adjusts for bNAb epitopes and challenge viruses, serum ID50 had a highly significant effect on infection risk (p < 0.001). The estimated ID50 to achieve 50%, 75%, and 95% protection was 91 (95% confidence interval [CI]: 55, 153), 219 (117, 410), and 685 (319, 1471), respectively. This analysis indicates that serum neutralizing titer against the relevant virus is a key parameter of protection and that protection from acquisition by a single bNAb might require substantial levels of neutralization at the time of exposure.

    Original languageEnglish (US)
    Pages (from-to)336-346.e3
    JournalCell Host and Microbe
    Volume26
    Issue number3
    DOIs
    StatePublished - Sep 11 2019

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    Keywords

    • SHIV challenge
    • broad neutralizing antibodies
    • correlates of protection
    • meta-analysis
    • non-human primate studies

    ASJC Scopus subject areas

    • Parasitology
    • Microbiology
    • Virology

    Cite this

    Pegu, A., Borate, B., Huang, Y., Pauthner, M. G., Hessell, A. J., Julg, B., Doria-Rose, N. A., Schmidt, S. D., Carpp, L. N., Cully, M. D., Chen, X., Shaw, G. M., Barouch, D. H., Haigwood, N. L., Corey, L., Burton, D. R., Roederer, M., Gilbert, P. B., Mascola, J. R., & Huang, Y. (2019). A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge. Cell Host and Microbe, 26(3), 336-346.e3. https://doi.org/10.1016/j.chom.2019.08.014