Characterization of cross-reactive monoclonal antibodies against SARS-CoV-1 and SARS-CoV-2: Implication for rational design and development of pan-sarbecovirus vaccines and neutralizing antibodies

Shibo Li; Jianbo Wu; Weiyu Jiang; Haiyan He; Yunjiao Zhou; Wei Wu; Yidan Gao; Minxiang Xie; Anqi Xia; Jiaying He; Qianqian Zhang; Yuru Han; Nan Wang; Guangqi Zhu; Qiujing Wang; Zheen Zhang; Christian T Mayer; Kang Wang; Xiangxi Wang; Junqing Wang; Zhenguo Chen; Shibo Jiang; Lei Sun; Rong Xia; Qiao Wang

doi:10.1002/jmv.28440

Characterization of cross-reactive monoclonal antibodies against SARS-CoV-1 and SARS-CoV-2: Implication for rational design and development of pan-sarbecovirus vaccines and neutralizing antibodies

J Med Virol. 2023 Feb;95(2):e28440. doi: 10.1002/jmv.28440.

Authors

Shibo Li¹, Jianbo Wu², Weiyu Jiang², Haiyan He³, Yunjiao Zhou², Wei Wu², Yidan Gao², Minxiang Xie², Anqi Xia², Jiaying He², Qianqian Zhang², Yuru Han², Nan Wang⁴, Guangqi Zhu¹, Qiujing Wang¹, Zheen Zhang¹, Christian T Mayer⁵, Kang Wang⁶, Xiangxi Wang⁶, Junqing Wang⁴, Zhenguo Chen⁷, Shibo Jiang², Lei Sun^{2

7}, Rong Xia⁸, Qiao Wang²

Affiliations

¹ Department of Infectious Disease, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, China.
² Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Fudan University, Shanghai, China.
³ Department of Hematology, Myeloma & Lymphoma Center, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
⁴ Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁶ CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
⁷ Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
⁸ Department of Transfusion Medicine, Shanghai Huashan Hospital, Fudan University, Shanghai, China.

Abstract

Emergence of various circulating SARS-CoV-2 variants of concern (VOCs) promotes the identification of pan-sarbecovirus vaccines and broadly neutralizing antibodies (bNAbs). Here, to characterize monoclonal antibodies cross-reactive against both SARS-CoV-1 and SARS-CoV-2 and to search the criterion for bNAbs against all emerging SARS-CoV-2, we isolated several SARS-CoV-1-cross-reactive monoclonal antibodies (mAbs) from a wildtype SARS-CoV-2 convalescent donor. These antibodies showed broad binding capacity and cross-neutralizing potency against various SARS-CoV-2 VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but failed to efficiently neutralize Omicron variant and its sublineages. Structural analysis revealed how Omicron sublineages, but not other VOCs, efficiently evade an antibody family cross-reactive against SARS-CoV-1 through their escape mutations. Further evaluation of a series of SARS-CoV-1/2-cross-reactive bNAbs showed a negative correlation between the neutralizing activities against SARS-CoV-1 and SARS-CoV-2 Omicron variant. Together, these results suggest the necessity of using cross-neutralization against SARS-CoV-1 and SARS-CoV-2 Omicron as criteria for rational design and development of potent pan-sarbecovirus vaccines and bNAbs.

Keywords: Omicron; SARS-CoV-1; SARS-CoV-2; broadly neutralizing antibody (bNAb); cross-reactivity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Broadly Neutralizing Antibodies
COVID-19*
Humans
SARS-CoV-2
Severe acute respiratory syndrome-related coronavirus*
Spike Glycoprotein, Coronavirus
Vaccines*

Substances

Antibodies, Neutralizing
Antibodies, Monoclonal
Broadly Neutralizing Antibodies
Antibodies, Viral
Vaccines
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Supplementary concepts

SARS-CoV-2 variants