Author:
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,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
Abstract
SummaryDeveloping broad coronavirus vaccines requires identifying and understanding the molecular basis of broadly neutralizing antibody (bnAb) spike sites. In our previous work, we identified sarbecovirus spike RBD group 1 and 2 bnAbs. We have now shown that many of these bnAbs can still neutralize highly mutated SARS-CoV-2 variants, including the XBB.1.5. Structural studies revealed that group 1 bnAbs use recurrent germline encoded CDRH3 features to interact with a conserved RBD region that overlaps with class 4 bnAb site. Group 2 bnAbs recognize a less well-characterized "site V" on the RBD and destabilize spike trimer. The site V has remained largely unchanged in SARS-CoV- 2 variants and is highly conserved across diverse sarbecoviruses, making it a promising target for broad coronavirus vaccine development. Our findings suggest that targeted vaccine strategies may be needed to induce effective B cell responses to escape resistant subdominant spike RBD bnAb sites.
Publisher
Cold Spring Harbor Laboratory