Identification of an immunogenic epitope and protective antibody against the furin cleavage site of SARS-CoV-2Research in context
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
Affiliations
Lili Li
Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China
Meiling Gao
Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China
Jie Li
Department of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China
Xuping Xie
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA
Hui Zhao
Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, China
Yanan Wang
Suzhou Func Biotech Inc, Suzhou, China
Xin Xu
Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China
Shulong Zu
Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China
Chunfeng Chen
Suzhou Func Biotech Inc, Suzhou, China
Dingyi Wan
AtaGenix Laboratories (Wuhan) Co., Ltd., Wuhan, China
Jing Duan
AtaGenix Laboratories (Wuhan) Co., Ltd., Wuhan, China
Jingfeng Wang
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
Saba R. Aliyari
Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA
Sarah Gold
Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA
Jicai Zhang
Department of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China
Cheng-Feng Qin
Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, China; Corresponding author.
Pei-Yong Shi
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Corresponding author.
Heng Yang
Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China; Corresponding author.
Genhong Cheng
Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA; Corresponding author.
Summary: 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 and BE2022728).
