Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition.
Peter B GilbertYunda HuangAllan C deCampShelly T KarunaYuanyuan ZhangCraig A MagaretElena E GiorgiBette T KorberPaul T EdlefsenRaabya RossenkhanMichal JuraskaErika RudnickiNidhi KocharYing HuangLindsay N CarppDan H BarouchNonhlanhla N MkhizeTandile HermanusPrudence KgagudiValerie BekkerHaajira KaldineRutendo E MapengoAmanda EatonElize DominCarley WestWenhong FengHaili TangKelly E SeatonJack HeptinstallCaroline BrackettKelvin ChiongGeorgia D TomarasPhilip AndrewBryan T MayerDaniel B ReevesMagdalena E SobieszczykSharana MahomedJorge SanchezCynthia GayJoseph MakhemaCarolyn WilliamsonJames I MullinsJohn HuralMyron S CohenLawrence CoreyDavid C MontefioriLynn MorrisPublished in: Nature medicine (2022)
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 80 ) 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 80 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 80 <200 against 90% of circulating viruses can be achieved by promising bnAb regimens engineered for long half-lives. We propose the PT 80 biomarker as a surrogate endpoint for evaluatinon of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines.