Broad neutralization of SARS-CoV-2 variants by an inhalable bispecific single-domain antibody

The effectiveness of SARS-CoV-2 vaccines and therapeutic antibodies have 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...

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Bibliographic Details
Published in:Cell Vol. 185; no. 8; p. 1389
Main Authors: Li, Cheng, Zhan, Wuqiang, Yang, Zhenlin, Tu, Chao, Hu, Gaowei, Zhang, Xiang, Song, Wenping, Du, Shujuan, Zhu, Yuanfei, Huang, Keke, Kong, Yu, Zhang, Meng, Mao, Qiyu, Gu, Xiaodan, Zhang, Yi, Xie, Youhua, Deng, Qiang, Song, Yuanlin, Chen, Zhenguo, Lu, Lu, Jiang, Shibo, Wu, Yanling, Sun, Lei, Ying, Tianlei
Format: Journal Article
Language:English
Published: United States 14.04.2022
Subjects:
Administration, Inhalation
Animals
Antibodies, Neutralizing
Antibodies, Viral
COVID-19
COVID-19 Vaccines - administration & dosage
Disease Models, Animal
Humans
Mice
SARS-CoV-2
Single-Domain Antibodies
Spike Glycoprotein, Coronavirus - chemistry
bispecific antibody
inhalation
SARS-CoV-2
broad neutralization
single-domain antibody
ISSN:1097-4172, 1097-4172
Online Access:Get more information
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Summary:The effectiveness of SARS-CoV-2 vaccines and therapeutic antibodies have 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 the Omicron variant receptor-binding domain recognized by broadly neutralizing antibodies. Furthermore, we generated a bispecific single-domain antibody that was able to simultaneously and synergistically bind these two regions on a single Omicron variant receptor-binding domain as revealed by cryo-EM structures. We demonstrated that this bispecific antibody can be effectively delivered to lung via inhalation administration and exhibits exquisite neutralization breadth and therapeutic efficacy in mouse models of SARS-CoV-2 infections. Importantly, this study also deciphered an uncommon and highly conserved cryptic epitope within the spike trimeric interface that may have implications for the design of broadly protective SARS-CoV-2 vaccines and therapeutics.
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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2022.03.009