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 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 Haigwood, Lawrence Corey, Dennis R. Burton, Mario Roederer, Peter B. Gilbert, John R. Mascola, Ying Huang

    Research output: Contribution to journalArticle

    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

    Fingerprint

    Simian Immunodeficiency Virus
    Passive Immunization
    Neutralizing Antibodies
    Meta-Analysis
    HIV
    Virus Diseases
    Primates
    Serum
    env Gene Products
    Viruses
    HIV-1
    Epitopes
    Logistic Models
    Confidence Intervals
    Infection

    Keywords

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

    ASJC Scopus subject areas

    • Parasitology
    • Microbiology
    • Virology

    Cite this

    A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge. / Pegu, Amarendra; Borate, Bhavesh; Huang, Yunda; Pauthner, Matthias G.; Hessell, Ann; Julg, Boris; Doria-Rose, Nicole A.; Schmidt, Stephen D.; Carpp, Lindsay N.; Cully, Michelle D.; Chen, Xuejun; Shaw, George M.; Barouch, Dan H.; Haigwood, Nancy; Corey, Lawrence; Burton, Dennis R.; Roederer, Mario; Gilbert, Peter B.; Mascola, John R.; Huang, Ying.

    In: Cell Host and Microbe, Vol. 26, No. 3, 11.09.2019, p. 336-346.e3.

    Research output: Contribution to journalArticle

    Pegu, A, Borate, B, Huang, Y, Pauthner, MG, Hessell, A, Julg, B, Doria-Rose, NA, Schmidt, SD, Carpp, LN, Cully, MD, Chen, X, Shaw, GM, Barouch, DH, Haigwood, N, Corey, L, Burton, DR, Roederer, M, Gilbert, PB, Mascola, JR & 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, vol. 26, no. 3, pp. 336-346.e3. https://doi.org/10.1016/j.chom.2019.08.014
    Pegu, Amarendra ; Borate, Bhavesh ; Huang, Yunda ; Pauthner, Matthias G. ; Hessell, Ann ; Julg, Boris ; Doria-Rose, Nicole A. ; Schmidt, Stephen D. ; Carpp, Lindsay N. ; Cully, Michelle D. ; Chen, Xuejun ; Shaw, George M. ; Barouch, Dan H. ; Haigwood, Nancy ; Corey, Lawrence ; Burton, Dennis R. ; Roederer, Mario ; Gilbert, Peter B. ; Mascola, John R. ; Huang, Ying. / A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge. In: Cell Host and Microbe. 2019 ; Vol. 26, No. 3. pp. 336-346.e3.
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