Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition.

Gilbert, Peter B; Huang, Yunda; deCamp, Allan C; Karuna, Shelly; Zhang, Yuanyuan; Magaret, Craig A; Giorgi, Elena E; Korber, Bette et al. · Nat Med · 2022

retrospective_cohort · Level III

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Abstract

The Antibody Mediated Prevention trials showed that the broadly neutralizing antibody (bnAb) VRC01 prevented acquisition of human immunodeficiency virus-1 (HIV-1) sensitive to VRC01. Using AMP trial data, here we show that the predicted serum neutralization 80% inhibitory dilution titer (PT<sub>80</sub>) biomarker-which quantifies the neutralization potency of antibodies in an individual's serum against an HIV-1 isolate-can be used to predict HIV-1 prevention efficacy. Similar to the results of nonhuman primate studies, an average PT<sub>80</sub> of 200 (meaning a bnAb concentration 200-fold higher than that required to reduce infection by 80% in vitro) against a population of probable exposing viruses was estimated to be required for 90% prevention efficacy against acquisition of these viruses. Based on this result, we suggest that the goal of sustained PT<sub>80</sub> <200 against 90% of circulating viruses can be achieved by promising bnAb regimens engineered for long half-lives. We propose the PT<sub>80</sub> biomarker as a surrogate endpoint for evaluatinon of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines.

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