Precise targeting of HIV broadly neutralizing antibody precursors in humans

• DOI: 10.1126/science.adv5572
• Publication Date: 2025-05-15T17:59:11Z
• Authors: Tom G. Caniels; Madhu Prabhakaran; Gabriel Ozorowski; Kellie J. MacPhee; Weiwei Wu; Karlijn van der S...; Sashank Agrawal; Ronald Derking; Emma I. M. M. Reiss; Katrina Millard; Martina Turroja; Aimee Desrosiers; Jeffrey Bethony; Elissa Malkin; Marinus H. Liesdek; Annelou van der Veen; Michelle Klouwens; Jonne L. Snitselaar; Joey H. Bouhuijs; Rhianna Bronson; Jalen Jean-Baptiste; Suprabhath Gajjala; Zahra Rikhtegaran...; Alison Benner; Mukundhan Ramaswami; Michael O. Duff; Yung-Wen Liu; Alicia H. Sato; Ju Yeong Kim; Isabel J. L. Baken; Catarina Mendes S...; Tom P. L. Bijl; Jacqueline van Ri...; Judith A. Burger; Albert Cupo; Anila Yasmeen; Swastik Phulera; Wen-Hsin Lee; Kipchoge N. Randall; Shiyu Zhang; Martin M. Corcoran; Isabel Regadas; Alex C. Sullivan; David M. Brown; Jennifer A. Bohl; Kelli M. Greene; Hongmei Gao; Nicole L. Yates; Sheetal Sawant; Jan M. Prins; Neeltje A. Kootstra; Stephen M. Kaminsky; Burc Barin; Farhad Rahaman; Margaret Meller; Vince Philiponis; Dagna S. Laufer; Angela Lombardo; Lindsey Mwoga; Solmaz Shotorbani; Drienna Holman; Richard A. Koup; Per Johan Klasse; Gunilla B. Karlss...; Georgia D. Tomaras; Marit J. van Gils; David C. Montefiori; Adrian B. McDermott; Ollivier Hyrien; John P. Moore; Ian A. Wilson; Andrew B. Ward; David J. Diemert; Godelieve J. de Bree; Sarah F. Andrews; Marina Caskey; Rogier W. Sanders

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 B , 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.