Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials

作者：Nonhlanhla N. Mkhize, Anna Yssel, Haajira Kaldine, Rebecca T. van Dorsten, Amanda S. Woodward Davis, Nicolas Beaume, David Matten, Bronwen E. Lambson, Tandile Modise, Prudence Kgagudi, Talita York, Dylan H. Westfall, Elena E. Giorgi, Bette Korber, Colin Anthony, Rutendo E. Mapengo, Valerie Bekker, Elizabeth Domin, Amanda Eaton, Wenjie Deng, Allan C. deCamp, Yunda Huang, Peter B. Gilbert, Asanda Gwashu-Nyangiwe, Ruwayhida Thebus, Nonkululeko Ndabambi, Dieter Mielke, Nyaradzo Mgodi, Shelly Karuna, Srilatha Edupuganti, Michael S. Seaman, Lawrence Corey, Myron S. Cohen, John Hural, M. Juliana McElrath, James I. Mullins, David C. Montefiori, Penny L. Moore, Carolyn Williamson, Lynn Morris · 发表于：PLoS Pathogens · 年份：2023 · DOI：10.1371/journal.ppat.1011469 · 被引用次数：57 · 研究领域：HIV Research and Treatment、HIV/AIDS drug development and treatment、Hepatitis C virus research

The VRC01 Antibody Mediated Prevention (AMP) efficacy trials conducted between 2016 and 2020 showed for the first time that passively administered broadly neutralizing antibodies (bnAbs) could prevent HIV-1 acquisition against bnAb-sensitive viruses. HIV-1 viruses isolated from AMP participants who acquired infection during the study in the sub-Saharan African (HVTN 703/HPTN 081) and the Americas/European (HVTN 704/HPTN 085) trials represent a panel of currently circulating strains of HIV-1 and offer a unique opportunity to investigate the sensitivity of the virus to broadly neutralizing antibodies (bnAbs) being considered for clinical development. Pseudoviruses were constructed using envelope sequences from 218 individuals. The majority of viruses identified were clade B and C; with clades A, D, F and G and recombinants AC and BF detected at lower frequencies. We tested eight bnAbs in clinical development (VRC01, VRC07-523LS, 3BNC117, CAP256.25, PGDM1400, PGT121, 10-1074 and 10E8v4) for neutralization against all AMP placebo viruses (n = 76). Compared to older clade C viruses (1998-2010), the HVTN703/HPTN081 clade C viruses showed increased resistance to VRC07-523LS and CAP256.25. At a concentration of 1μg/ml (IC80), predictive modeling identified the triple combination of V3/V2-glycan/CD4bs-targeting bnAbs (10-1074/PGDM1400/VRC07-523LS) as the best against clade C viruses and a combination of MPER/V3/CD4bs-targeting bnAbs (10E8v4/10-1074/VRC07-523LS) as the best against cla...