tetano
Editor, Senior Moderator
J Biomed Sci
. 2022 Dec 22;29(1):108.
doi: 10.1186/s12929-022-00891-2.
Monoclonal antibodies against S2 subunit of spike protein exhibit broad reactivity toward SARS-CoV-2 variants
Shih-Han Ko[SUP] 1 [/SUP], Wan-Yu Chen[SUP] 2 [/SUP], Shih-Chieh Su[SUP] 2 [/SUP], Hsiu-Ting Lin[SUP] 2 [/SUP], Feng-Yi Ke[SUP] 1 [/SUP], Kang-Hao Liang[SUP] 1 [/SUP], Fu-Fei Hsu[SUP] 1 [/SUP], Monika Kumari[SUP] 2 [/SUP], Chi-Yu Fu[SUP] 2 [/SUP], Han-Chung Wu[SUP] 3 4 [/SUP]
Affiliations
Abstract
Background: The 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.
Methods: Using 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.
Results: Among 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 (IC[SUB]50[/SUB] = 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.
Conclusion: Since 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.
Keywords: B cell epitope; Monoclonal antibody; Phage display; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Spike (S) protein.
. 2022 Dec 22;29(1):108.
doi: 10.1186/s12929-022-00891-2.
Monoclonal antibodies against S2 subunit of spike protein exhibit broad reactivity toward SARS-CoV-2 variants
Shih-Han Ko[SUP] 1 [/SUP], Wan-Yu Chen[SUP] 2 [/SUP], Shih-Chieh Su[SUP] 2 [/SUP], Hsiu-Ting Lin[SUP] 2 [/SUP], Feng-Yi Ke[SUP] 1 [/SUP], Kang-Hao Liang[SUP] 1 [/SUP], Fu-Fei Hsu[SUP] 1 [/SUP], Monika Kumari[SUP] 2 [/SUP], Chi-Yu Fu[SUP] 2 [/SUP], Han-Chung Wu[SUP] 3 4 [/SUP]
Affiliations
- PMID: 36550570
- DOI: 10.1186/s12929-022-00891-2
Abstract
Background: The 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.
Methods: Using 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.
Results: Among 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 (IC[SUB]50[/SUB] = 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.
Conclusion: Since 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.
Keywords: B cell epitope; Monoclonal antibody; Phage display; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Spike (S) protein.