VRC01 exerted differential pressure on HIV-1 Env from subtypes B and C that continued in the first weeks post-diagnosis in the AMP trials

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ID: 328046
2026
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Abstract
BACKGROUND: The Antibody Mediated Prevention trials (HVTN 703 and HVTN 704) demonstrated that infusions of the bnAb VRC01 prevented HIV-1 acquisition with viruses sensitive to VRC01 neutralization. We evaluated how VRC01 epitope distances differed across groups in the trials. METHODS: We calculated VRC01 epitope distances (a 3D structure informed measure of how the VRC01 epitope in a sequence differs from that epitope in known VRC01 sensitive strains) to compare >35,000 Envelopes sampled from 172 participants with mostly subtype C viruses in HVTN 703 and subtype B in HVTN 704. RESULTS: At the first visit with detectable HIV-1, we found fewer distinct VRC01 epitopes in the sequences from participants in the VRC01 high-dose group in HVTN 704 (p=0.054), suggesting that some epitope variants were blocked in these participants who harbored subtype B viruses. In both trials, VRC01 epitope distances were significantly larger in the VRC01 high-dose groups than in the placebo groups (p≤0.010). Moreover, sequences sampled in the first month after diagnosis showed that the rate of change in VRC01 epitope distances was significantly higher in the VRC01 groups than in the placebo in the HVTN 703 trial (p≤0.036). CONCLUSIONS: These findings show the impact of sieve acquisition (variants blocked among subtype B viruses) and post-acquisition (stronger impact of VRC01-mediated escape in subtype C) effects, highlighting a complex intersection between HIV-1 subtypes, escape pathways and antibody-mediated prevention. The differential pressure exerted by VRC01 on subtype B vs. C viruses emphasizes that escape pathways need to be considered when selecting bnAbs for clinical trials.
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Authors Hongjun Bai, Michal Juraska, Craig A. Magaret, Anna Yssel, Raabya Rossenkhan, Ben Murrell, Bethany L. Dearlove, Éric Lewitus, Allan C. deCamp, Elena E Giorgi, James Ludwig, Dylan H. Westfall, Wenjie Deng, Lennie Chen, Hong Zhao, Alec Pankow, Tanmoy Bhattacharya, Talita York, Asanda Gwashu-Nyangiwe, Nonkululeko Ndabambi, Ruwayhida Thebus, Julie A. Ake, Sandhya Vasan, April Randhawa, John A Hural, Sri Edupuganti, Nyaradzo Mgodi, Shelly Karuna, Lynn Morris, David C. Montefiori, Myron S. Cohen, Lawrence Corey, Paul T. Edlefsen, M Julianna McElrath, Peter B Gilbert, Carolyn Williamson, James I Mullins, Morgane Rolland
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Journal The Journal of infectious diseases
Year 2026
DOI
10.1093/infdis/jiag454
URL
https://doi.org/10.1093/infdis/jiag454
Keywords Keywords not found

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