Precise targeting of HIV broadly neutralizing antibody precursors in humans

Authors

• Tom G. Caniels, Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
• Madhu Prabhakaran, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Gabriel Ozorowski, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
• Kellie J. MacPhee, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
• Weiwei Wu, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Karlijn van der Straten, Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
• Sashank Agrawal, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
• Ronald Derking, Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
• Emma I. Reiss, Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
• Katrina Millard, Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
• Martina Turroja, Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
• Aimee Desrosiers, Vaccine Research Unit, The George Washington University, Washington, DC, USA.
• Jeffrey Bethony, Vaccine Research Unit, The George Washington University, Washington, DC, USA.
• Elissa Malkin, Vaccine Research Unit, The George Washington University, Washington, DC, USA.
• Marinus H. Liesdek, Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
• Annelou van der Veen, Department of Internal Medicine, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
• Michelle Klouwens, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, Netherlands.
• Jonne L. Snitselaar, Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
• Joey H. Bouhuijs, Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
• Rhianna Bronson, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Jalen Jean-Baptiste, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Suprabhath Gajjala, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Zahra Rikhtegaran Tehrani, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Alison Benner, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Mukundhan Ramaswami, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Michael O. Duff, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
• Yung-Wen Liu, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
• Alicia H. Sato, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
• Ju Yeong Kim, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
• Isabel J. Baken, Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
• Catarina Mendes Silva, Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
• Tom P. Bijl, Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location AMC, Amsterdam, Netherlands.

Document Type

Journal Article

Publication Date

5-15-2025

Journal

Science (New York, N.Y.)

DOI

10.1126/science.adv5572

Abstract

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, induced bnAb precursors of the VRC01-class at a high frequency in the majority of vaccine recipients. These bnAb precursors, that 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.

APA Citation

Caniels, Tom G.; Prabhakaran, Madhu; Ozorowski, Gabriel; MacPhee, Kellie J.; Wu, Weiwei; van der Straten, Karlijn; Agrawal, Sashank; Derking, Ronald; Reiss, Emma I.; Millard, Katrina; Turroja, Martina; Desrosiers, Aimee; Bethony, Jeffrey; Malkin, Elissa; Liesdek, Marinus H.; van der Veen, Annelou; Klouwens, Michelle; Snitselaar, Jonne L.; Bouhuijs, Joey H.; Bronson, Rhianna; Jean-Baptiste, Jalen; Gajjala, Suprabhath; Rikhtegaran Tehrani, Zahra; Benner, Alison; Ramaswami, Mukundhan; Duff, Michael O.; Liu, Yung-Wen; Sato, Alicia H.; Kim, Ju Yeong; Baken, Isabel J.; Mendes Silva, Catarina; and Bijl, Tom P., "Precise targeting of HIV broadly neutralizing antibody precursors in humans" (2025). GW Authored Works. Paper 7256.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7256

Department

Microbiology, Immunology, and Tropical Medicine