ジャーナル: Science / 年: 2025 タイトル: Precise targeting of HIV broadly neutralizing antibody precursors in humans. 著者: Tom G Caniels / Madhu Prabhakaran / Gabriel Ozorowski / Kellie J MacPhee / Weiwei Wu / Karlijn van der Straten / Sashank Agrawal / Ronald Derking / Emma I M M Reiss / Katrina Millard / ...著者: Tom G Caniels / Madhu Prabhakaran / Gabriel Ozorowski / Kellie J MacPhee / Weiwei Wu / Karlijn van der Straten / 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 Tehrani / Alison Benner / Mukundhan Ramaswami / Michael O Duff / Yung-Wen Liu / Alicia H Sato / Ju Yeong Kim / Isabel J L Baken / Catarina Mendes Silva / Tom P L Bijl / Jacqueline van Rijswijk / 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 Karlsson Hedestam / 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 / 要旨: 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 ...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.