Identification of an immunogenic epitope and protective antibody against the furin cleavage site of SARS-CoV-2

Lili Li; Meiling Gao; Jie Li; Xuping Xie; Hui Zhao; Yanan Wang; Xin Xu; Shulong Zu; Chunfeng Chen; Dingyi Wan; Jing Duan; Jingfeng Wang; Saba R Aliyari; Sarah Gold; Jicai Zhang; Cheng-Feng Qin; Pei-Yong Shi; Heng Yang; Genhong Cheng

doi:10.1016/j.ebiom.2022.104401

Identification of an immunogenic epitope and protective antibody against the furin cleavage site of SARS-CoV-2

EBioMedicine. 2023 Jan:87:104401. doi: 10.1016/j.ebiom.2022.104401. Epub 2022 Dec 9.

Authors

Lili Li¹, Meiling Gao¹, Jie Li², Xuping Xie³, Hui Zhao⁴, Yanan Wang⁵, Xin Xu¹, Shulong Zu¹, Chunfeng Chen⁵, Dingyi Wan⁶, Jing Duan⁶, Jingfeng Wang⁷, Saba R Aliyari⁸, Sarah Gold⁸, Jicai Zhang², Cheng-Feng Qin⁹, Pei-Yong Shi¹⁰, Heng Yang¹¹, Genhong Cheng¹²

Affiliations

¹ Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China.
² Department of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
³ Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
⁴ Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, China.
⁵ Suzhou Func Biotech Inc, Suzhou, China.
⁶ AtaGenix Laboratories (Wuhan) Co., Ltd., Wuhan, China.
⁷ Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
⁸ Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
⁹ Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, China. Electronic address: qincf@bmi.ac.cn.
¹⁰ Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: peshi@utmb.edu.
¹¹ Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China. Electronic address: yh@ism.cams.cn.
¹² Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA. Electronic address: gcheng@mednet.ucla.edu.

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the global coronavirus disease 2019 (COVID-19) pandemic, contains a unique, four amino acid (aa) "PRRA" insertion in the spike (S) protein that creates a transmembrane protease serine 2 (TMPRSS2)/furin cleavage site and enhances viral infectivity. More research into immunogenic epitopes and protective antibodies against this SARS-CoV-2 furin cleavage site is needed.

Methods: Combining computational and experimental methods, we identified and characterized an immunogenic epitope overlapping the furin cleavage site that detects antibodies in COVID-19 patients and elicits strong antibody responses in immunized mice. We also identified a high-affinity monoclonal antibody from COVID-19 patient peripheral blood mononuclear cells; the antibody directly binds the furin cleavage site and protects against SARS-CoV-2 infection in a mouse model.

Findings: The presence of "PRRA" amino acids in the S protein of SARS-CoV-2 not only creates a furin cleavage site but also generates an immunogenic epitope that elicits an antibody response in COVID-19 patients. An antibody against this epitope protected against SARS-CoV-2 infection in mice.

Interpretation: The immunogenic epitope and protective antibody we have identified may augment our strategy in handling COVID-19 epidemic.

Funding: The National Natural Science Foundation of China (82102371, 91542201, 81925025, 82073181, and 81802870), the Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2021-I2M-1-047 and 2022-I2M-2-004), the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (2020-PT310-006, 2019XK310002, and 2018TX31001), the National Key Research and Development Project of China (2020YFC0841700), US National Institute of Health (NIH) funds grant AI158154, University of California Los Angeles (UCLA) AI and Charity Treks, and UCLA DGSOM BSCRC COVID-19 Award Program. H.Y. is supported by Natural Science Foundation of Jiangsu Province (BK20211554 andBE2022728).

Keywords: COVID-19; Furin site; Immunogenic epitope; S protein; SARS-CoV-2.

MeSH terms

Animals
Antibodies
Antibody Formation
COVID-19*
Epitopes
Furin / chemistry
Furin / metabolism
Leukocytes, Mononuclear / metabolism
Mice
SARS-CoV-2* / metabolism

Substances

Furin
Epitopes
Antibodies

Grants and funding

R01 AI158154/AI/NIAID NIH HHS/United States