Cell reports · 2025
Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Song Ge, Yuan Meng, Liu Hejun, Capozzola Tazio, Lin Ryan N, Torres Jonathan L, He Wan-Ting, Musharrafieh Rami, Dueker Katharina, Zhou Panpan, Callaghan Sean, Mishra Nitesh, Yong Peter, Anzanello Fabio, Avillion Gabriel, Vo Anh Lina, Li Xuduo, Zhang Yuexiu, Makhdoomi Muzamil, Feng Ziqi, Zhu Xueyong, Peng Linghang, Nemazee David, Safonova Yana, Briney Bryan, Ward Andrew B, Burton Dennis R, Wilson Ian A, Andrabi Raiees
Аннотация
Developing broad coronavirus vaccines hinges on identifying and understanding the molecular basis of conserved spike epitopes targeted by broadly neutralizing antibodies (bnAbs). Building on our earlier work identifying sarbecovirus receptor-binding domain (RBD) group 1 and 2 bnAbs, we now show that several of these antibodies retain neutralizing activity against highly mutated SARS-CoV-2 variants, including BA.2.86 and JN.1. Structural studies reveal that group 1 bnAbs use recurrent germline-encoded heavy-chain complementarity-determining region 3 (CDRH3) features to interact with a conserved RBD region that overlaps with class 4 bnAb site. Group 2 bnAbs recognize a less well-defined "site V" on the RBD and destabilize spike trimer. Notably, site V remains largely unchanged across SARS-CoV-2 variants and is conserved among diverse sarbecoviruses, highlighting its potential as a broad vaccine target. Our findings underscore the need for targeted vaccine strategies to induce immunofocused B cell responses to escape resistant subdominant spike RBD bnAb epitopes.