Peer-reviewedCC BY 4.0Nature Microbiology
Prophylactic treatment with broadly neutralizing antibody VRC01 selects for escape mutants after infection in Antibody-Mediated Prevention trials
19 affiliations
- 1Division of Medical Virology, Institute of Infectious Disease and Molecular Medicine and Wellcome CIDRI-Africa Centre, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
- 2National Health Laboratory Service, Johannesburg, South Africa
- 3Centre for the AIDS Programme of Research in South Africa, University of Kwa-Zulu Natal, Durban, South Africa
- 4SA MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- 5National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa
- 6Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA USA
- 7US Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD USA
- 8Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD USA
- 9Department of Global Health, University of Washington, Seattle, WA USA
- 10Department of Microbiology, University of Washington, Seattle, WA USA
- 11Present Address: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA USA
- 12Los Alamos National Laboratory, Los Alamos, NM USA
- 13Santa Fe Institute, Santa Fe, NM USA
- 14Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Solna, Sweden
- 15University of Zimbabwe College of Health Sciences Clinical Trials Research Centre, Harare, Zimbabwe
- 16Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA USA
- 17Department of Surgery, Duke University Medical Center, Durham, NC USA
- 18Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC USA
- 19Wits Infectious Diseases and Oncology Research Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Abstract
Broadly neutralizing antibodies (bnAbs) show promise in HIV prevention, yet viral escape remains a challenge. In the Antibody-Mediated Prevention (AMP) trials, the CD4 binding site (CD4bs) bnAb VRC01 blocked acquisition by VRC01-sensitive strains. However, its influence on viral evolution post acquisition is not fully understood. Here we analysed 11,730 HIV envelope sequences generated during the AMP trials from 47 participants, identifying VRC01-mediated de novo escape mutations in 8 of 26 VRC01-treated participants but none in 21 placebo participants. These mutations were found at very low frequencies (<1%) in globally circulating viruses, suggesting that they may confer fitness costs. Escape mutations, primarily located in the Loop-D and β23/V5 regions of Env, conferred cross-resistance to several CD4bs bnAbs; however, more potent CD4bs bnAbs such as N6 and 1–18 largely retained their activity. Our findings demonstrate that prophylactic VRC01 can select for viral escape after infection, underscoring the need for next-generation bnAbs with improved breadth and potency to enhance durability and efficacy of antibody-based HIV prevention.
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BibTeX
@article{williamson2026prophylactic,
title = {{Prophylactic treatment with broadly neutralizing antibody VRC01 selects for escape mutants after infection in Antibody-Mediated Prevention trials}},
author = {Carolyn Williamson and Lyle Curry and Nonhlanhla N. Mkhize and Elena E. Giorgi and Craig A. Magaret and Bronwen E. Lambson and Sinethemba Bhebhe and Haajira Kaldine and Thandeka Moyo-Gwete and Morgane Rolland and Raabya Rossenkhan and Nina Marie G. Garcia and Chivonne Moodley and Anna Yssel and Yunda Huang and Alaine A. Marsden and Daniel B. Reeves and Bryan T. Mayer and Roger E. Bumgarner and Nicolas Beaume and Dylan H. Westfall and Michal Juraska and Allan C. DeCamp and Hugh Murrell and Hongjun Bai and Wenjie Deng and Alec P. Pankow and Tanmoy Bhattacharya and Talita York and Nonkululeko Ndabambi and Lennie Chen and Hong Zhao and Asanda Gwashu-Nyangiri and Ruwayhida Thebus and Paula Cohen and Ben Murrell and Shelly Karuna and John Hural and Nyaradzo Mgodi and Srilatha Edupuganti and Lynn Morris and David Montefiori and M. Juliana McElrath and Myron S. Cohen and Lawrence Corey and Paul T. Edlefsen and Peter B. Gilbert and Penny L. Moore and James I. Mullins},
journal = {Nature Microbiology},
year = {2026},
month = sep,
doi = {10.1038/s41564-026-02467-4},
url = {https://doi.org/10.1038/s41564-026-02467-4},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Prophylactic treatment with broadly neutralizing antibody VRC01 selects for escape mutants after infection in Antibody-Mediated Prevention trials
AU - Carolyn Williamson
AU - Lyle Curry
AU - Nonhlanhla N. Mkhize
AU - Elena E. Giorgi
AU - Craig A. Magaret
AU - Bronwen E. Lambson
AU - Sinethemba Bhebhe
AU - Haajira Kaldine
AU - Thandeka Moyo-Gwete
AU - Morgane Rolland
AU - Raabya Rossenkhan
AU - Nina Marie G. Garcia
AU - Chivonne Moodley
AU - Anna Yssel
AU - Yunda Huang
AU - Alaine A. Marsden
AU - Daniel B. Reeves
AU - Bryan T. Mayer
AU - Roger E. Bumgarner
AU - Nicolas Beaume
AU - Dylan H. Westfall
AU - Michal Juraska
AU - Allan C. DeCamp
AU - Hugh Murrell
AU - Hongjun Bai
AU - Wenjie Deng
AU - Alec P. Pankow
AU - Tanmoy Bhattacharya
AU - Talita York
AU - Nonkululeko Ndabambi
AU - Lennie Chen
AU - Hong Zhao
AU - Asanda Gwashu-Nyangiri
AU - Ruwayhida Thebus
AU - Paula Cohen
AU - Ben Murrell
AU - Shelly Karuna
AU - John Hural
AU - Nyaradzo Mgodi
AU - Srilatha Edupuganti
AU - Lynn Morris
AU - David Montefiori
AU - M. Juliana McElrath
AU - Myron S. Cohen
AU - Lawrence Corey
AU - Paul T. Edlefsen
AU - Peter B. Gilbert
AU - Penny L. Moore
AU - James I. Mullins
PY - 2026
DA - 2026/09/28
JO - Nature Microbiology
DO - 10.1038/s41564-026-02467-4
UR - https://doi.org/10.1038/s41564-026-02467-4
AB - Broadly neutralizing antibodies (bnAbs) show promise in HIV prevention, yet viral escape remains a challenge. In the Antibody-Mediated Prevention (AMP) trials, the CD4 binding site (CD4bs) bnAb VRC01 blocked acquisition by VRC01-sensitive strains. However, its influence on viral evolution post acquisition is not fully understood. Here we analysed 11,730 HIV envelope sequences generated during the AMP trials from 47 participants, identifying VRC01-mediated de novo escape mutations in 8 of 26 VRC01-treated participants but none in 21 placebo participants. These mutations were found at very low frequencies (<1%) in globally circulating viruses, suggesting that they may confer fitness costs. Escape mutations, primarily located in the Loop-D and β23/V5 regions of Env, conferred cross-resistance to several CD4bs bnAbs; however, more potent CD4bs bnAbs such as N6 and 1–18 largely retained their activity. Our findings demonstrate that prophylactic VRC01 can select for viral escape after infection, underscoring the need for next-generation bnAbs with improved breadth and potency to enhance durability and efficacy of antibody-based HIV prevention.
SN - 2058-5276
ER -