Broad neutralization of SARS-CoV-2 variants by an inhalable bispecific single-domain antibody
Cheng Li; Wuqiang Zhan; Zhenlin Yang; Chao Tu; Yuanfei Zhu; Wenping Song; Keke Huang; Xiaodan Gu; Yu Kong; Xiang Zhang; Meng Zhang; Yi Zhang; Youhua Xie; Qiang Deng; Zhenguo Chen; Lu Lu; Shibo Jiang; Lei Sun; Yanling Wu; Tianlei Ying.
Preprint
en Inglés
| PREPRINT-BIORXIV | ID: ppbiorxiv-474535
The effectiveness of SARS-CoV-2 vaccines and therapeutic antibodies has been limited by the continuous emergence of viral variants, and by the restricted diffusion of antibodies from circulation into the sites of respiratory virus infection. Here, we report the identification of two highly conserved regions on Omicron variant RBD recognized by broadly neutralizing antibodies. Based on this finding, we generated a bispecific single-domain antibody that was able to simultaneously and synergistically bind these two regions on a single Omicron variant RBD as revealed by Cryo-EM structures. This inhalable antibody exhibited exquisite neutralization breadth and therapeutic efficacy in mouse models of SARS-CoV-2 infections. The structures also deciphered an uncommon cryptic epitope within the spike trimeric interface that may have implications for the design of broadly protective SARS-CoV-2 vaccines and therapeutics.
Texto completo
Documentos relacionados