Precise targeting of HIV broadly neutralizing antibody precursors in humans
A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled phase 1 human clinical trial, the recombinant, germline-targeting envelope glycoprotein (Env) trimer BG505 SOSIP.v4.1-GT1.1, adjuvanted with AS01<sub>B</sub>, induced bnAb precursors of the VRC01-class at a high frequency in the majority of vaccine recipients. These bnAb precursors, which target the CD4 receptor binding site, had undergone somatic hypermutation characteristic of the VRC01-class. A subset of isolated VRC01-class monoclonal antibodies neutralized wild-type pseudoviruses and was structurally extremely similar to bnAb VRC01. These results further support germline-targeting approaches for human HIV vaccine design and demonstrate atomic-level manipulation of B cell responses with rational vaccine design.
Authors
- Sheetal Sawant (ORCID: https://orcid.org/0000-0002-1109-7907)
- Adrian B. McDermott (ORCID: https://orcid.org/0000-0003-0616-9117)
- Kellie J. MacPhee (ORCID: https://orcid.org/0009-0008-0993-4009)
- David C. Montefiori (ORCID: https://orcid.org/0000-0003-0856-6319)
- Ian A. Wilson (ORCID: https://orcid.org/0000-0002-6469-2419)
- David Joseph Diemert (ORCID: https://orcid.org/0000-0002-2789-0512)
- Alison Benner
- Kelli Greene (ORCID: https://orcid.org/0009-0008-6919-9288)
- Martina Turroja (ORCID: https://orcid.org/0000-0001-9640-0559)
- Weiwei Wu (ORCID: https://orcid.org/0009-0008-6015-9167)
- Swastik Phulera (ORCID: https://orcid.org/0000-0002-1272-7712)
- Marit J. van Gils (ORCID: https://orcid.org/0000-0003-3422-8161)
- Zahra Rikhtegaran Tehrani (ORCID: https://orcid.org/0000-0002-1127-1290)
- Burc Barin
- Richard A. Koup (ORCID: https://orcid.org/0000-0002-3090-7282)
- John P. Moore (ORCID: https://orcid.org/0000-0002-9902-6096)
- Isabel Regadas
- Stephen M. Kaminsky (ORCID: https://orcid.org/0000-0003-1869-834X)
- Martin Corcoran (ORCID: https://orcid.org/0000-0002-2774-0936)
- Marina Caskey (ORCID: https://orcid.org/0000-0003-1727-8693)
- Aimee Desrosiers
- Catarina Mendes Silva
- Suprabhath Gajjala (ORCID: https://orcid.org/0000-0002-3828-1958)
- Mukundhan Ramaswami (ORCID: https://orcid.org/0000-0002-4804-5676)
- Jacqueline van Rijswijk
- Georgia D. Tomaras (ORCID: https://orcid.org/0000-0001-8076-1931)
- Judith A. Burger (ORCID: https://orcid.org/0000-0002-7311-9921)
- Sashank Agrawal (ORCID: https://orcid.org/0000-0001-8549-9602)
- Anila Yasmeen (ORCID: https://orcid.org/0000-0002-2386-8991)
- Tom P. L. Bijl
- Albert Cupo (ORCID: https://orcid.org/0000-0001-7579-3525)
- Emma I. M. M. Reiss (ORCID: https://orcid.org/0009-0006-4695-0628)
- Annelou van der Veen
- J Kim
- Sarah F. Andrews (ORCID: https://orcid.org/0000-0002-2583-1949)
- Gabriel Ozorowski (ORCID: https://orcid.org/0000-0002-9695-8138)
- Jan M. Prins (ORCID: https://orcid.org/0000-0002-5415-8933)
- Godelieve J. de Bree (ORCID: https://orcid.org/0000-0002-5852-5833)
- Joey H. Bouhuijs (ORCID: https://orcid.org/0000-0002-6074-8542)
- Per Johan Klasse (ORCID: https://orcid.org/0000-0001-8222-278X)
- Farhad Rahaman (ORCID: https://orcid.org/0000-0003-4069-4580)
- Jennifer A. Bohl (ORCID: https://orcid.org/0000-0001-6057-1858)
- Dagna Laufer
- Ronald Derking (ORCID: https://orcid.org/0000-0002-6074-8542)
- Karlijn van der Straten (ORCID: https://orcid.org/0000-0001-6373-9302)
- Drienna Holman
- Michelle J. Klouwens (ORCID: https://orcid.org/0000-0002-3515-6748)
- Nicole L. Yates
- Hongmei Gao (ORCID: https://orcid.org/0000-0002-2468-8589)
- David M. Brown (ORCID: https://orcid.org/0000-0003-4463-8316)
- Marinus H. Liesdek
- Neeltje A. Kootstra (ORCID: https://orcid.org/0000-0001-9429-7754)
- Andrew B. Ward (ORCID: https://orcid.org/0000-0001-7153-3769)
- Alicia Sato (ORCID: https://orcid.org/0000-0001-8371-8007)
- Tom G. Caniels (ORCID: https://orcid.org/0000-0001-9580-157X)
- Rhianna Bronson (ORCID: https://orcid.org/0009-0009-5513-3250)
- Angela Lombardo (ORCID: https://orcid.org/0000-0003-0182-133X)
- Wen-Hsin Lee (ORCID: https://orcid.org/0000-0001-9445-6671)
- Jonne L. Snitselaar (ORCID: https://orcid.org/0000-0002-6074-8542)
- Gunilla B. Karlsson Hedestam (ORCID: https://orcid.org/0000-0001-7255-9047)
- Elissa Malkin (ORCID: https://orcid.org/0000-0003-0943-5433)
- Yung-Wen Liu (ORCID: https://orcid.org/0000-0003-0524-3952)
- Rogier W. Sanders (ORCID: https://orcid.org/0000-0002-2324-8573)
- Madhu Prabhakaran (ORCID: https://orcid.org/0000-0002-1981-9054)
- Katrina G. Millard (ORCID: https://orcid.org/0000-0003-2247-3178)
- Kurt T. Randall (ORCID: https://orcid.org/0009-0005-7553-3893)
- Ollivier Hyrien (ORCID: https://orcid.org/0000-0003-1909-2542)
- Shiyu Zhang (ORCID: https://orcid.org/0000-0003-4586-0605)
- Jalen Jean-Baptiste
- Isabel J. L. Baken (ORCID: https://orcid.org/0009-0006-6818-1401)
- Jeffrey M. Bethony (ORCID: https://orcid.org/0000-0003-0364-6176)
- Andrew Sullivan
- Michael O. Duff
- Margaret Meller
- Vince Philiponis
- Lindsey Mwoga
- Solmaz Shotorbani
Institutions
- Scripps Research Institute (US)
- National Institutes of Health (US)
- International AIDS Vaccine Initiative (US)
- George Washington University (US)
- Cornell University (US)
- Foundation for the National Institutes of Health (US)
- Karolinska Institutet (SE)
- Fred Hutch Cancer Center (US)
- Amsterdam Neuroscience (NL)
- Emmes (United States) (US)
- Duke Medical Center (US)
- National Institute of Allergy and Infectious Diseases (US)
- Amsterdam University Medical Centers (NL)
- Weill Cornell Medicine (US)
- Rockefeller University (US)
- University of Amsterdam (NL)
Publication Details
- Journal
- Science
- Published
- 2025-05-15
- DOI
- https://doi.org/10.1126/science.adv5572
- Citations
- 28
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 29.02
Funders
- U.S. Department of Energy
- Bill and Melinda Gates Foundation
- International AIDS Vaccine Initiative
- Vaccine Research Center
- Vetenskapsrådet
- National Institutes of Health
- Office of Science
- Brookhaven National Laboratory
- NHLBI Division of Intramural Research