Antibody evasion of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2, and BA.3 sub-lineages

Jingwen Ai; Xun Wang; Xinyi He; Xiaoyu Zhao; Yi Zhang; Yuchao Jiang; Minghui Li; Yuchen Cui; Yanjia Chen; Rui Qiao; Lin Li; Lulu Yang; Yi Li; Zixin Hu; Wenhong Zhang; Pengfei Wang

doi:10.1016/j.chom.2022.05.001

Antibody evasion of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2, and BA.3 sub-lineages

Cell Host Microbe. 2022 Aug 10;30(8):1077-1083.e4. doi: 10.1016/j.chom.2022.05.001. Epub 2022 May 8.

Authors

Jingwen Ai¹, Xun Wang², Xinyi He³, Xiaoyu Zhao², Yi Zhang¹, Yuchao Jiang⁴, Minghui Li², Yuchen Cui², Yanjia Chen², Rui Qiao², Lin Li², Lulu Yang², Yi Li⁵, Zixin Hu⁶, Wenhong Zhang⁷, Pengfei Wang⁸

Affiliations

¹ Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
² State Key Laboratory of Genetic Engineering, Shanghai Institute of Infectious Disease and Biosecurity, School of Life Sciences, Fudan University, Shanghai, China.
³ State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences and Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China.
⁴ Pigentech Lab Limited, Shanghai, China.
⁵ State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences and Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China; International Human Phenome Institutes, Shanghai, China.
⁶ State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences and Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China; Artificial Intelligence Innovation and Incubation Institute, Fudan University, Shanghai, China. Electronic address: huzixin@fudan.edu.cn.
⁷ Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Medical Molecular Virology (MOE/MOH), Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: zhangwenhong@fudan.edu.cn.
⁸ State Key Laboratory of Genetic Engineering, Shanghai Institute of Infectious Disease and Biosecurity, School of Life Sciences, Fudan University, Shanghai, China. Electronic address: pengfei_wang@fudan.edu.cn.

Abstract

The SARS-CoV-2 Omicron variant has evolved into four sub-lineages-BA.1, BA.1.1, BA.2, and BA.3-with BA.2 becoming dominant worldwide. We and others have reported antibody evasion of BA.1 and BA.2, but side-by-side comparisons of Omicron sub-lineages to vaccine-elicited or monoclonal antibody (mAb)-mediated neutralization are necessary. Using VSV-based pseudovirus, we report that sera from individuals vaccinated by two doses of an inactivated whole-virion vaccine shows weak to no neutralization activity, while homologous or heterologous boosters markedly improve neutralization titers against all Omicron sub-lineages. We also present neutralization profiles against a 20 mAb panel, including 10 authorized or approved, against the Omicron sub-lineages, along with mAb mapping against single or combinatorial spike mutations. Most mAbs lost neutralizing activity, while some demonstrate distinct neutralization patterns among Omicron sub-lineages, reflecting antigenic differences. Collectively, our results suggest the Omicron sub-lineages threaten the neutralization efficacy of current vaccines and antibody therapeutics, highlighting the importance of vaccine boosters.

Keywords: BA.1; BA.1.1; BA.2; BA.3; BBIBP-CorV; Omicron; SARS-CoV-2; antibody; booster; vaccine.

MeSH terms

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
COVID-19*
Humans
Neutralization Tests
SARS-CoV-2* / genetics
Vaccines, Inactivated

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Vaccines, Inactivated

Supplementary concepts

SARS-CoV-2 variants