美国加州理工学院Pamela J. Bjorkman研究团队发现，马赛克RBD纳米颗粒引发的中和单克隆抗体与保守的沙贝病毒表位结合。该研究于2022年10月26日在线发表于国际一流学术期刊《免疫》。

Title: Neutralizing monoclonal antibodies elicited by mosaic RBD nanoparticles bind conserved sarbecovirus epitopes

Author: Chengcheng Fan, Alexander A. Cohen, Miso Park, Alfur Fu-Hsin Hung, Jennifer R. Keeffe, Priyanthi N.P. Gnanapragasam, Yu E. Lee, Han Gao, Leesa M. Kakutani, Ziyan Wu, Harry Kleanthous, Kathryn E. Malecek, John C. Williams, Pamela J. Bjorkman

Issue&Volume: 2022-10-26

Abstract: Increased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding domains (RBDs) from eight sarbecoviruses (mosaic-8 RBD-nanoparticles) efficiently elicits cross-reactive polyclonal antibodies against conserved sarbecovirus RBD epitopes. Here, we identified monoclonal antibodies (mAbs) capable of cross-reactive binding and neutralization of animal sarbecoviruses and SARS-CoV-2 variants by screening single mouse B-cells secreting IgGs that bind two or more sarbecovirus RBDs. Single-particle cryo-EM structures of antibody–spike complexes, including a Fab-Omicron complex, mapped neutralizing mAbs to conserved class 1/4 RBD epitopes. Structural analyses revealed neutralization mechanisms, potentials for intra-spike trimer crosslinking by IgGs, and induced changes in trimer upon Fab binding. In addition, we identified a mAb resembling Bebtelovimab, an EUA-approved human class 3 anti-RBD mAb. These results support using mosaic RBD-nanoparticle vaccination to generate and identify therapeutic pan-sarbecovirus and pan-variant mAbs.

DOI: 10.1016/j.immuni.2022.10.019

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00560-X