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

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 c...

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Detalles Bibliográficos
Autores principales: Li, Lili, Gao, Meiling, Li, Jie, Xie, Xuping, Zhao, Hui, Wang, Yanan, Xu, Xin, Zu, Shulong, Chen, Chunfeng, Wan, Dingyi, Duan, Jing, Wang, Jingfeng, Aliyari, Saba R., Gold, Sarah, Zhang, Jicai, Qin, Cheng-Feng, Shi, Pei-Yong, Yang, Heng, Cheng, Genhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732504/
https://www.ncbi.nlm.nih.gov/pubmed/36508877
http://dx.doi.org/10.1016/j.ebiom.2022.104401
Descripción
Sumario: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 10.13039/501100001809National Natural Science Foundation of China (82102371, 91542201, 81925025, 82073181, and 81802870), the 10.13039/501100019018Chinese 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 10.13039/501100005150Chinese Academy of Medical Sciences (2020-PT310-006, 2019XK310002, and 2018TX31001), the 10.13039/501100012166National Key Research and Development Project of China (2020YFC0841700), 10.13039/100000002US National Institute of Health (NIH) funds grant AI158154, 10.13039/100007185University of California Los Angeles (UCLA) AI and Charity Treks, and 10.13039/100007185UCLA DGSOM BSCRC COVID-19 Award Program. H.Y. is supported by 10.13039/501100004608Natural Science Foundation of Jiangsu Province (BK20211554 andBE2022728).

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