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

    Nature medicine, 09/2022, Letnik: 28, Številka: 9
    Journal Article

    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 ) 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 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 <200 against 90% of circulating viruses can be achieved by promising bnAb regimens engineered for long half-lives. We propose the PT biomarker as a surrogate endpoint for evaluatinon of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines.