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

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

Cell (2022-03-29)
Cheng Li, Wuqiang Zhan, Zhenlin Yang, Chao Tu, Gaowei Hu, Xiang Zhang, Wenping Song, Shujuan Du, Yuanfei Zhu, Keke Huang, Yu Kong, Meng Zhang, Qiyu Mao, Xiaodan Gu, Yi Zhang, Youhua Xie, Qiang Deng, Yuanlin Song, Zhenguo Chen, Lu Lu, Shibo Jiang, Yanling Wu, Lei Sun, Tianlei Ying
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Protein Standard Mix 15 - 600 kDa, for size exclusion chromatography
Roche
High Fidelity PCR Master, sufficient for ≤200 reactions, kit of 1 (2 components), suitable for PCR