Monoclonal antibodies against S2 subunit of spike protein exhibit broad reactivity toward SARS-CoV-2 variants

Journal of Biomedical Science

Research

Fu-Fei Hsu¹  Kang-Hao Liang¹  Shih-Han Ko¹  Feng-Yi Ke¹  Han-Chung Wu²  Hsiu-Ting Lin³  Shih-Chieh Su³  Chi-Yu Fu³  Wan-Yu Chen³  Monika Kumari³ 

[1]Biomedical Translation Research Center (BioTReC), Academia Sinica, 11529, Taipei, Taiwan

[2]Biomedical Translation Research Center (BioTReC), Academia Sinica, 11529, Taipei, Taiwan

[3]Institute of Cellular and Organismic Biology, Academia Sinica, 11529, Taipei, Taiwan

[4]Institute of Cellular and Organismic Biology, Academia Sinica, 11529, Taipei, Taiwan

关键词: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2);    Spike (S) protein;    Monoclonal antibody;    Phage display;    B cell epitope;   

DOI  :  10.1186/s12929-022-00891-2

 received in 2022-09-25, accepted in 2022-12-06,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) harbor diverse spike (S) protein sequences, which can greatly influence the efficacies of therapeutics. Therefore, it would be of great value to develop neutralizing monoclonal antibodies (mAbs) that can broadly recognize multiple variants.MethodsUsing an mRNA-LNP immunization strategy, we generated several mAbs that specifically target the conserved S2 subunit of SARS-CoV-2 (B-S2-mAbs). These mAbs were assessed for their neutralizing activity with pseudotyped viruses and binding ability for SARS-CoV-2 variants.ResultsAmong these mAbs, five exhibited strong neutralizing ability toward the Gamma variant and also recognized viral S proteins from the Wuhan, Alpha, Beta, Gamma, Delta and Omicron (BA.1, BA.2 and BA.5) variants. Furthermore, we demonstrated the broad reactivities of these B-S2-mAbs in several different applications, including immunosorbent, immunofluorescence and immunoblotting assays. In particular, B-S2-mAb-2 exhibited potent neutralization of Gamma variant (IC50 = 0.048 µg/ml) in a pseudovirus neutralization assay. The neutralizing epitope of B-S2-mAb-2 was identified by phage display as amino acid residues 1146–1152 (DSFKEEL) in the S2 subunit HR2 domain of SARS-CoV-2.ConclusionSince there are not many mAbs that can bind the S2 subunit of SARS-CoV-2 variants, our set of B-S2-mAbs may provide important materials for basic research and potential clinical applications. Importantly, our study results demonstrate that the viral S2 subunit can be targeted for the production of cross-reactive antibodies, which may be used for coronavirus detection and neutralization.

【 授权许可】

CC BY   
© The Author(s) 2022

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