Authors
Nonhlanhla N Mkhize, Anna EJ Yssel, Haajira Kaldine, Rebecca T van Dorsten, Amanda S Woodward Davis, Nicolas Beaume, David Matten, Bronwen 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 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 Montefiori, Penny L Moore, Carolyn Williamson, Lynn Morris
Publication date
2023/6/29
Journal
PLoS Pathogens
Volume
19
Issue
6
Pages
e1011469
Publisher
Public Library of Science
Description
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 clade B viruses, due to low coverage of V2-glycan directed bnAbs against clade B viruses. Overall, the AMP …
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