Publications Date
Authors
Gilbert PB, Huang Y, deCamp AC, Karuna S, Zhang Y, Magaret CA, Giorgi EE, Korber B, Edlefsen PT, Rossenkhan R, Juraska M, Rudnicki E, Kochar N, Huang Y, Carpp LN, Barouch DH, Mkhize NN, Hermanus T, Kgagudi P, Bekker V, Kaldine H, Mapengo RE, Eaton A, Domin E, West C, Feng W, Tang H, Seaton KE, Heptinstall J, Brackett C, Chiong K, Tomaras GD, Andrew P, Mayer BT, Reeves DB, Sobieszczyk ME, Garrett N, Sanchez J, Gay C, Makhema J, Williamson C, Mullins JI, Hural J, Cohen MS, Corey L, Montefiori DC, Morris L.
Journal
Nat Med
PMID
35995954 PMCID:
PMCID
PMC9499869
DOI
10.1038/s41591-022-01953-6
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 (PT80) 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 PT80 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 PT80 <200 against 90% of circulating viruses can be achieved by promising bnAb regimens engineered for long half-lives. We propose the PT80 biomarker as a surrogate endpoint for evaluatinon of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines.