Sequential vaccination matures VRC01-class HIV-1 neutralizing antibodies in humans

Inducing a broadly neutralizing antibody (bnAb) response is a key goal of HIV-1 vaccine development. Despite significant progress, it is unknown whether vaccine-primed B cells can be reactivated and matured to secrete bona fide bnAbs. In the IAVI C107/C110 single-arm, open-label human trial, VRC01-class memory B cells previously primed by the GT1.1 germline-targeting envelope glycoprotein (Env) trimer were reactivated by a BG505 SOSIP.664 trimer boost. Somatic hypermutation in the activated B cells drove higher antibody affinity for the CD4-binding site on fully glycosylated, heterologous Env trimers. Three VRC01-class monoclonal antibodies derived from independent B cell lineages neutralized 18-31% of 119 viruses in a globally diverse panel. This work advances the HIV-1 germline-targeting vaccination concept from proof-of-priming towards proof-of-breadth and defines a benchmark for bnAb induction.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-10-26
DOI
https://doi.org/10.64898/2026.10.21.760679
Primary Topic
HIV Research and Treatment
Type
preprint

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preprint

Sequential vaccination matures VRC01-class HIV-1 neutralizing antibodies in humans

Sheetal S. Sawant, Kellie J. MacPhee, David C. Montefiori, Katrina Saam et al.
bioRxiv (Cold Spring Harbor Laboratory)
HIV Research and Treatment
preprint

Sequential vaccination matures VRC01-class HIV-1 neutralizing antibodies in humans

Sheetal S. Sawant, Kellie J. MacPhee, David C. Montefiori, Katrina Saam, Deanna Dong, Rosemarie D. Mason, David Joseph Diemert, Alison Benner, Kelli Greene, Martina Turroja, Swastik Phulera, Marit J. van Gils, Zahra Rikhtegaran Tehrani, Burc Barin, Richard A. Koup, John P. Moore, Marina F. Caskey, Aimee A. Desrosiers, Weiwei Wu, Catarina Mendes Silva, Suprabhath R. Gajjala, Jacqueline van Rijswijk, Georgia D. Tomaras, Judith A. Burger, Lebohang Molife, Sashank Agrawal, Claudio Yurdadön, Tom P. L. Bijl, Albert Cupo, Annelou van der Veen, Sarah F. Andrews, Gabriel Ozorowski, Godelieve J. de Bree, Joey H. Bouhuijs, Per Johan Klasse, Jennifer A. Bohl, Solmaz Shotorbani, Dagna S. Laufer, Ethan Wilson, Karlijn van der Straten, Drienna Holman, Michelle J. Klouwens, Nicole L. Yates, David M. Brown, Neeltje A. Kootstra, Alicia Sato, Tom G. Caniels, Eva I.M. Schumacher, Rhianna Bronson, Angela M. Lombardo, Michael S. Seaman, Jonne L. Snitselaar, Elissa M. Malkin, Rogier W. Sanders, Madhu S. Prabhakaran, Katrina G. Millard, Ollivier Hyrien, Vincent Philiponis, Isabel J. L. Baken, Andrew B. Ward, Jeffrey Michael Bethony, Michael O. Duff, Andy S. Tran, Lindsey Mwoga, Hongmei Gao, Annie F Mabushi, Ian A. Wilson, Agnes M. Harskamp, Ju Yeong Kim, Alex C. Sullivan, Meghna Chandrasekar, Mukundhan Ramaswami
preprint en

Abstract

Inducing a broadly neutralizing antibody (bnAb) response is a key goal of HIV-1 vaccine development. Despite significant progress, it is unknown whether vaccine-primed B cells can be reactivated and matured to secrete bona fide bnAbs. In the IAVI C107/C110 single-arm, open-label human trial, VRC01-class memory B cells previously primed by the GT1.1 germline-targeting envelope glycoprotein (Env) trimer were reactivated by a BG505 SOSIP.664 trimer boost. Somatic hypermutation in the activated B cells drove higher antibody affinity for the CD4-binding site on fully glycosylated, heterologous Env trimers. Three VRC01-class monoclonal antibodies derived from independent B cell lineages neutralized 18-31% of 119 viruses in a globally diverse panel. This work advances the HIV-1 germline-targeting vaccination concept from proof-of-priming towards proof-of-breadth and defines a benchmark for bnAb induction.

bioRxiv (Cold Spring Harbor Laboratory)
Scripps Research Institute (US), National Institutes of Health (US), International AIDS Vaccine Initiative (US), Beth Israel Deaconess Medical Center (US), Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), Infectious Disease Research Institute (US), Duke University (US), George Washington University (US), Cornell University (US), Foundation for the National Institutes of Health (US), Amsterdam UMC Location University of Amsterdam (NL), Fred Hutch Cancer Center (US), Amsterdam Neuroscience (NL), Emmes (United States) (US), National Institute of Allergy and Infectious Diseases (US), Amsterdam University Medical Centers (NL), Weill Cornell Medicine (US), Vaccine Research Center (US), Rockefeller University (US), University of Amsterdam (NL)
U.S. Department of Energy, Bill and Melinda Gates Foundation, International AIDS Vaccine Initiative, Vaccine Research Center, Amsterdam University Medical Centers, National Institutes of Health, Office of Science, Brookhaven National Laboratory, NHLBI Division of Intramural Research
HIV Research and Treatment
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