Monoclonal antibodies against S2 subunit of spike protein exhibit broad reactivity toward SARS-CoV-2 variants
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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-12-01
|
| Series: | Journal of Biomedical Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12929-022-00891-2 |
| _version_ | 1797977342572756992 |
|---|---|
| author | Shih-Han Ko Wan-Yu Chen Shih-Chieh Su Hsiu-Ting Lin Feng-Yi Ke Kang-Hao Liang Fu-Fei Hsu Monika Kumari Chi-Yu Fu Han-Chung Wu |
| author_facet | Shih-Han Ko Wan-Yu Chen Shih-Chieh Su Hsiu-Ting Lin Feng-Yi Ke Kang-Hao Liang Fu-Fei Hsu Monika Kumari Chi-Yu Fu Han-Chung Wu |
| author_sort | Shih-Han Ko |
| collection | DOAJ |
| description | 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 (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. 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. |
| first_indexed | 2024-04-11T05:05:17Z |
| format | Article |
| id | doaj.art-738750f514c14a22a2f66f17d012271e |
| institution | Directory Open Access Journal |
| issn | 1423-0127 |
| language | English |
| last_indexed | 2024-04-11T05:05:17Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-738750f514c14a22a2f66f17d012271e2022-12-25T12:24:32ZengBMCJournal of Biomedical Science1423-01272022-12-0129111310.1186/s12929-022-00891-2Monoclonal antibodies against S2 subunit of spike protein exhibit broad reactivity toward SARS-CoV-2 variantsShih-Han Ko0Wan-Yu Chen1Shih-Chieh Su2Hsiu-Ting Lin3Feng-Yi Ke4Kang-Hao Liang5Fu-Fei Hsu6Monika Kumari7Chi-Yu Fu8Han-Chung Wu9Biomedical Translation Research Center (BioTReC), Academia SinicaInstitute of Cellular and Organismic Biology, Academia SinicaInstitute of Cellular and Organismic Biology, Academia SinicaInstitute of Cellular and Organismic Biology, Academia SinicaBiomedical Translation Research Center (BioTReC), Academia SinicaBiomedical Translation Research Center (BioTReC), Academia SinicaBiomedical Translation Research Center (BioTReC), Academia SinicaInstitute of Cellular and Organismic Biology, Academia SinicaInstitute of Cellular and Organismic Biology, Academia SinicaBiomedical Translation Research Center (BioTReC), Academia SinicaAbstract 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 (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. 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.https://doi.org/10.1186/s12929-022-00891-2Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Spike (S) proteinMonoclonal antibodyPhage displayB cell epitope |
| spellingShingle | Shih-Han Ko Wan-Yu Chen Shih-Chieh Su Hsiu-Ting Lin Feng-Yi Ke Kang-Hao Liang Fu-Fei Hsu Monika Kumari Chi-Yu Fu Han-Chung Wu Monoclonal antibodies against S2 subunit of spike protein exhibit broad reactivity toward SARS-CoV-2 variants Journal of Biomedical Science Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike (S) protein Monoclonal antibody Phage display B cell epitope |
| title | Monoclonal antibodies against S2 subunit of spike protein exhibit broad reactivity toward SARS-CoV-2 variants |
| title_full | Monoclonal antibodies against S2 subunit of spike protein exhibit broad reactivity toward SARS-CoV-2 variants |
| title_fullStr | Monoclonal antibodies against S2 subunit of spike protein exhibit broad reactivity toward SARS-CoV-2 variants |
| title_full_unstemmed | Monoclonal antibodies against S2 subunit of spike protein exhibit broad reactivity toward SARS-CoV-2 variants |
| title_short | Monoclonal antibodies against S2 subunit of spike protein exhibit broad reactivity toward SARS-CoV-2 variants |
| title_sort | monoclonal antibodies against s2 subunit of spike protein exhibit broad reactivity toward sars cov 2 variants |
| topic | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike (S) protein Monoclonal antibody Phage display B cell epitope |
| url | https://doi.org/10.1186/s12929-022-00891-2 |
| work_keys_str_mv | AT shihhanko monoclonalantibodiesagainsts2subunitofspikeproteinexhibitbroadreactivitytowardsarscov2variants AT wanyuchen monoclonalantibodiesagainsts2subunitofspikeproteinexhibitbroadreactivitytowardsarscov2variants AT shihchiehsu monoclonalantibodiesagainsts2subunitofspikeproteinexhibitbroadreactivitytowardsarscov2variants AT hsiutinglin monoclonalantibodiesagainsts2subunitofspikeproteinexhibitbroadreactivitytowardsarscov2variants AT fengyike monoclonalantibodiesagainsts2subunitofspikeproteinexhibitbroadreactivitytowardsarscov2variants AT kanghaoliang monoclonalantibodiesagainsts2subunitofspikeproteinexhibitbroadreactivitytowardsarscov2variants AT fufeihsu monoclonalantibodiesagainsts2subunitofspikeproteinexhibitbroadreactivitytowardsarscov2variants AT monikakumari monoclonalantibodiesagainsts2subunitofspikeproteinexhibitbroadreactivitytowardsarscov2variants AT chiyufu monoclonalantibodiesagainsts2subunitofspikeproteinexhibitbroadreactivitytowardsarscov2variants AT hanchungwu monoclonalantibodiesagainsts2subunitofspikeproteinexhibitbroadreactivitytowardsarscov2variants |