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. 2022 Sep 29;66(1):165–179. doi: 10.1007/s11427-022-2166-y

An antibody cocktail with broadened mutational resistance and effective protection against SARS-CoV-2

Chunyun Sun 1,#, Hang Chi 2,#, Fei Yuan 3,#, Jing Li 1, Ji Yang 1, Aihua Zheng 3, Fei Wang 1, Lingling Sun 1, Yanjing Zhang 1, Ping Hu 1, Lihua Jiao 1, Yongqiang Deng 2,✉, Liangzhi Xie 1,4,5,✉
PMCID: PMC9527072  PMID: 36184693

Abstract

Neutralizing antibodies have been proven to be highly effective in treating mild and moderate COVID-19 patients, but continuous emergence of SARS-CoV-2 variants poses significant challenges. Antibody cocktail treatments reduce the risk of escape mutants and resistance. In this study, a new cocktail composed of two highly potent neutralizing antibodies (HB27 and H89Y) was developed, whose binding epitope is different from those cocktails that received emergency use authorization. This cocktail showed more potent and balanced neutralizing activities (IC50 0.9–11.3 ng mL−1) against a broad spectrum of SARS-CoV-2 variants over individual HB27 or H89Y antibodies. Furthermore, the cocktail conferred more effective protection against the SARS-CoV-2 Beta variant in an aged murine model than monotherapy. It was shown to prevent SARS-CoV-2 mutational escape in vitro and effectively neutralize 61 types of pseudoviruses harbouring single amino acid mutation originated from variants and escape strains of Bamlanivimab, Casirivimab and Imdevimab with IC50 of 0.6–65 ng mL−1. Despite its breadth of variant neutralization, the HB27+H89Y combo and EUA cocktails lost their potencies against Omicron variant. Our results provide important insights that new antibody cocktails covering different epitopes are valuable tools to counter virus mutation and escape, highlighting the need to search for more conserved epitopes to combat Omicron.

Supporting Information

The supporting information is available online at 10.1007/s11427-022-2166-y. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

Keywords: SARS-CoV-2, COVID-19, epitopes, antibody cocktail, mutational escape

Supplementary Material

11427_2022_2166_MOESM1_ESM.pdf (437.2KB, pdf)

An Antibody Cocktail with Broadened Mutational Resistance and Effective Protection Against SARS-CoV-2

Acknowledgements

This work was supported by the National Key Research and Development Project of China (2021YEF0201700).

Footnotes

Compliance and ethics

The author(s) declare that they have no conflict of interest.

Contributed equally to this work

Contributor Information

Yongqiang Deng, Email: dengyq1977@126.com.

Liangzhi Xie, Email: LX@sinocelltech.com.

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Supplementary Materials

11427_2022_2166_MOESM1_ESM.pdf (437.2KB, pdf)

An Antibody Cocktail with Broadened Mutational Resistance and Effective Protection Against SARS-CoV-2

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