Identification of conserved linear epitopes in the SARS-CoV-2 receptor-binding region using monoclonal antibodies.

Yang, Yujie; Zhou, Liling; Mo, Chuncong; Hu, Longbo; Zhou, Zhichao; Fan, Ye; Liu, Wenkuan; Li, Xiao; Zhou, Rong; Tian, Xingui

Yang, Yujie; Zhou, Liling; Mo, Chuncong; Hu, Longbo; Zhou, Zhichao; Fan, Ye; Liu, Wenkuan; Li, Xiao; Zhou, Rong; Tian, Xingui.

Affiliation

Yang Y; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510182, China.
Zhou L; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510182, China.
Mo C; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510182, China.
Hu L; State Key Laboratory of Respiratory Disease, Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, 511436, China.
Zhou Z; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510182, China.
Fan Y; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510182, China.
Liu W; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510182, China.
Li X; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510182, China.
Zhou R; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510182, China.
Tian X; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510182, China.

Heliyon ; 9(6): e16847, 2023 Jun.

Article in En | MEDLINE | ID: mdl-37292282

ABSTRACT

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused millions of cases of infections, leading to a global health emergency. The SARS-CoV-2 spike (S) protein plays the most important role in viral infection, and S1 subunit and its receptor-binding domain (RBD) are widely considered the most attractive vaccine targets. The RBD is highly immunogenic and its linear epitopes are important for vaccine development and therapy, but linear epitopes on the RBD have rarely been reported. In this study, 151 mouse monoclonal antibodies (mAbs) against the SARS-CoV-2 S1 protein were characterized and used to identify epitopes. Fifty-one mAbs reacted with eukaryotic SARS-CoV-2 RBD. Sixty-nine mAbs reacted with the S proteins of Omicron variants B.1.1.529 and BA.5, indicating their potential as rapid diagnostic materials. Three novel linear epitopes of RBD, R6 (391CFTNVYADSFVIRGD405), R12 (463PFERDISTEIYQAGS477), and R16 (510VVVLSFELLHAPAT523), were identified; these were highly conserved in SARS-CoV-2 variants of concern and could be detected in the convalescent serum of COVID-19 patients. From pseudovirus neutralization assays, some mAbs including one detecting R12 were found to possess neutralizing activity. Together, from the reaction of mAbs with eukaryotic RBD (N501Y), RBD (E484K), and S1 (D614G), we found that a single amino acid mutation in the SARS-CoV-2 S protein may cause a structural alteration, exerting substantial impact on mAb recognition. Our results could, therefore, help us better understand the function of the SARS-CoV-2 S protein and develop diagnostic tools for COVID-19.

Key words

Epitope; Monoclonal antibody; Receptor-binding domain; SARS-CoV-2; Spike protein

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