Precise targeting of HIV broadly neutralizing antibody precursors in humans

• 成果类型: Article
• 署名作者: Caniels, Tom G.; Prabhakaran, Madhu; Ozorowski, Gabriel; MacPhee, Kellie J.; Wu, Weiwei; van der Straten, Karlijn; Agrawal, Sashank; Derking, Ronald; Reiss, Emma I. M. M.; 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. L.; Mendes Silva, Catarina; Bijl, Tom P. L.; van Rijswijk, Jacqueline; Burger, Judith A.; Cupo, Albert; Yasmeen, Anila; Phulera, Swastik; Lee, Wen-Hsin; Randall Jr, Kipchoge N.; Zhang, Shiyu; Corcoran, Martin M.; Regadas, Isabel; Sullivan, Alex C.; Brown, David M.; Bohl, Jennifer A.; Greene, Kelli M.; Gao, Hongmei; Yates, Nicole L.; Sawant, Sheetal; Prins, Jan M.; Kootstra, Neeltje A.; Kaminsky, Stephen M.; Barin, Burc; Rahaman, Farhad; Meller, Margaret; Philiponis, Vince; Laufer, Dagna S.; Lombardo, Angela; Mwoga, Lindsey; Shotorbani, Solmaz; Holman, Drienna; Koup, Richard A.; Klasse, Per Johan; Karlsson Hedestam, Gunilla B.; Tomaras, Georgia D.; van Gils, Marit J.; Montefiori, David C.; Mcdermott, Adrian B.; Hyrien, Ollivier; Moore, John P.; Wilson, Ian A.; Ward, Andrew B.; Diemert, David J.; de Bree, Godelieve J.; Andrews, Sarah F.; Caskey, Marina; Sanders, Rogier W.
• 署名单位: University of Amsterdam; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Scripps Research Institute; Fred Hutchinson Cancer Center; Rockefeller University; George Washington University; University of Amsterdam; Cornell University; Weill Cornell Medicine; Karolinska Institutet; National Institutes of Health (NIH) - USA; Duke University; University of Amsterdam; Cornell University; Weill Cornell Medicine; International AIDS Vaccine Initiative; Scripps Research Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11344
• DOI: 10.1126/science.adv5572
• 发表日期: 2025-07-31
• 关键词: cryo-em; monoclonal-antibodies; envelope; vaccine; binding; potent; maturation; immunogenicity; identification; responses

摘要

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 AS01B, 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.