Citation Information

Peter B Gilbert, Yunda Huang, Allan C deCamp, Shelly Karuna, Yuanyuan Zhang, Craig A Magaret, Elena E Giorgi, Bette Korber, Paul T Edlefsen, Raabya Rossenkhan, Michal Juraska, Erika Rudnicki, Nidhi Kochar, Ying Huang, Lindsay N Carpp, Dan H Barouch, Nonhlanhla N Mkhize, Tandile Hermanus, Prudence Kgagudi, Valerie Bekker, Haajira Kaldine, Rutendo E Mapengo, Amanda Eaton, Elize Domin, Carley West, Wenhong Feng, Haili Tang, Kelly E Seaton, Jack Heptinstall, Caroline Brackett, Kelvin Chiong, Georgia D Tomaras, Philip Andrew, Bryan T Mayer, Daniel B Reeves, Magdalena E Sobieszczyk, Nigel Garrett, Jorge Sanchez, Cynthia Gay, Joseph Makhema, Carolyn Williamson, James I Mullins, John Hural, Myron S Cohen, Lawrence Corey, David C Montefiori, Lynn Morris (2022). Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition. Nature Medicine 2022 Sep.;28(9):1924-1932. (pubmed) (doi)

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 evaluation of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines.