Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials

作者：Carolyn Williamson, Chivonne Moodley, Craig A. Magaret, Elena E. Giorgi, Morgane Rolland, Dylan H. Westfall, Anna Yssel, Wenjie Deng, Raabya Rossenkhan, Nonhlanhla N. Mkhize, Lennie Chen, Hong Zhao, Tanmoy Bhattacharya, Alec Pankow, Ben Murrell, Talita York, Asanda Gwashu-Nyangiwe, Nonkululeko Ndabambi, Ruwayhida Thebus, Paula Marantz Cohen, Bronwen E. Lambson, Haajira Kaldine, Sinethemba Bhebhe, Michal Juraska, Hongjun Bai, Allan C. deCamp, James P. Ludwig, Cindy Molitor, Nicolas Beaume, David Matten, Yunda Huang, Lily Zhang, Daniel B. Reeves, Bryan T. Mayer, Shelly Karuna, John Hural, Lynn Morris, David C. Montefiori, Roger E. Bumgarner, Penny L. Moore, Paul T. Edlefsen, Srilatha Edupuganti, Nyaradzo Mgodi, M. Juliana McElrath, Myron S. Cohen, Lawrence Corey, Peter B. Gilbert, James I. Mullins · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2025 · DOI：10.1101/2025.07.01.659979 · 被引用次数：1 · 研究领域：HIV Research and Treatment、Monoclonal and Polyclonal Antibodies Research、T-cell and B-cell Immunology

ABSTRACT In the HIV antibody mediated prevention (AMP) trials, the broadly neutralizing antibody VRC01 demonstrated protective efficacy against new diagnoses with susceptible HIV strains. To understand how VRC01 shaped breakthrough infections, we performed deep sequencing on 172 participants in the placebo and treatment arms, generating 63,444 gag-Δpol (2.5 kb) and 53,088 rev-env-Δnef (3 kb) sequences. Sequences were classified into transmitted founder lineages (TFLs), and infections with multiple distinct lineages were determined. Multilineage infections were detected in ∼38% of participants in both the African (HVTN 703/HPTN 081) and Americas/Europe (HVTN 704/HPTN 085) cohorts, regardless of placebo or treatment group, or cohort. The high levels of multilineage infections could be attributed to minor lineages (<5% abundance) identified in 20% of participants. Infection with VRC01 discordant viruses (IC80s >3-fold different) was observed in 40% of multilineage infections, with a trend toward greater intra-host neutralization differences with increasing VRC01 dose (Jonckheere-Terpstra test, p=0.072). In six VRC01 treated participants who acquired both sensitive (IC80<1µg/ml) and resistant viruses (IC80>3µg/ml), the sensitive lineages declined over time. Recombination was pervasive, observed in 63% of multilineage infections at the time of HIV diagnosis. In one treated participant infected with VRC01 discordant lineages, recombinant viruses preferentially inherited...