A meta-analysis of passive immunization studies shows that serum-neutralizing antibody titer associates withprotection against SHIV challenge

September 11, 2019

Publication type

Journal Article

Journal

Cell Host Microbe

Volume and Number

26(3)

Authors

Pegu A, Borate B, Huang Y, Pauthner MG, Hessell AJ, Julg B, Doria-Rose NA, Schmidt SD, Carpp LN, Cully MD, Chen X, Shaw GM, Barouch DH, Haigwood NL, Corey L, Burton DR, Roederer M, Gilbert PB, Mascola JR, Huang Y.

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.