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

Journal Article (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 (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.

Full Text

Duke Authors

Cited 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

Published Date

  • September 2022

Published In

Volume / Issue

  • 28 / 9

Start / End Page

  • 1924 - 1932

PubMed ID

  • 35995954

Pubmed Central ID

  • PMC9499869

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

Digital Object Identifier (DOI)

  • 10.1038/s41591-022-01953-6


  • eng

Conference Location

  • United States