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Targeting intra-viral conserved nucleocapsid (N) proteins as novel vaccines against SARS-CoVs.
Biosci Rep. 2021 09 30; 41(9)BR

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global pandemic of the Coronavirus disease in late 2019 (COVID-19). Vaccine development efforts have predominantly been aimed at 'Extra-viral' Spike (S) protein as vaccine vehicles, but there are concerns regarding 'viral immune escape' since multiple mutations may enable the mutated virus strains to escape from immunity against S protein. The 'Intra-viral' Nucleocapsid (N-protein) is relatively conserved among mutant strains of coronaviruses during spread and evolution. Herein, we demonstrate novel vaccine candidates against SARS-CoV-2 by using the whole conserved N-protein or its fragment/peptides. Using ELISA assay, we showed that high titers of specific anti-N antibodies (IgG, IgG1, IgG2a, IgM) were maintained for a reasonably long duration (> 5 months), suggesting that N-protein is an excellent immunogen to stimulate host immune system and robust B-cell activation. We synthesized three peptides located at the conserved regions of N-protein among CoVs. One peptide showed as a good immunogen for vaccination as well. Cytokine arrays on post-vaccination mouse sera showed progressive up-regulation of various cytokines such as IFN-γ and CCL5, suggesting that TH1 associated responses are also stimulated. Furthermore, vaccinated mice exhibited an elevated memory T cells population. Here, we propose an unconventional vaccine strategy targeting the conserved N-protein as an alternative vaccine target for coronaviruses. Moreover, we generated a mouse monoclonal antibody specifically against an epitope shared between SARS-CoV and SARS-CoV-2, and we are currently developing the First-in-Class humanized anti-N-protein antibody to potentially treat patients infected by various CoVs in the future.

Authors+Show Affiliations

Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.Lee Kong Chian School of Medicine, Singapore 308232.Department of Radiology, University of California San Diego, San Diego, CA 92103, USA.Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260. INTRA-ImmuSG Private Limited, Singapore 079903.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34519332

Citation

Thura, Min, et al. "Targeting Intra-viral Conserved Nucleocapsid (N) Proteins as Novel Vaccines Against SARS-CoVs." Bioscience Reports, vol. 41, no. 9, 2021.
Thura M, Sng JXE, Ang KH, et al. Targeting intra-viral conserved nucleocapsid (N) proteins as novel vaccines against SARS-CoVs. Biosci Rep. 2021;41(9).
Thura, M., Sng, J. X. E., Ang, K. H., Li, J., Gupta, A., Hong, J. M., Hong, C. W., & Zeng, Q. (2021). Targeting intra-viral conserved nucleocapsid (N) proteins as novel vaccines against SARS-CoVs. Bioscience Reports, 41(9). https://doi.org/10.1042/BSR20211491
Thura M, et al. Targeting Intra-viral Conserved Nucleocapsid (N) Proteins as Novel Vaccines Against SARS-CoVs. Biosci Rep. 2021 09 30;41(9) PubMed PMID: 34519332.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting intra-viral conserved nucleocapsid (N) proteins as novel vaccines against SARS-CoVs. AU - Thura,Min, AU - Sng,Joel Xuan En, AU - Ang,Koon Hwee, AU - Li,Jie, AU - Gupta,Abhishek, AU - Hong,Jimmy Ming, AU - Hong,Cheng William, AU - Zeng,Qi, PY - 2021/06/23/received PY - 2021/08/30/revised PY - 2021/09/13/accepted PY - 2021/9/15/pubmed PY - 2021/10/6/medline PY - 2021/9/14/entrez KW - Coronavirus KW - Nucleocapsid protein KW - Vaccine JF - Bioscience reports JO - Biosci Rep VL - 41 IS - 9 N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global pandemic of the Coronavirus disease in late 2019 (COVID-19). Vaccine development efforts have predominantly been aimed at 'Extra-viral' Spike (S) protein as vaccine vehicles, but there are concerns regarding 'viral immune escape' since multiple mutations may enable the mutated virus strains to escape from immunity against S protein. The 'Intra-viral' Nucleocapsid (N-protein) is relatively conserved among mutant strains of coronaviruses during spread and evolution. Herein, we demonstrate novel vaccine candidates against SARS-CoV-2 by using the whole conserved N-protein or its fragment/peptides. Using ELISA assay, we showed that high titers of specific anti-N antibodies (IgG, IgG1, IgG2a, IgM) were maintained for a reasonably long duration (> 5 months), suggesting that N-protein is an excellent immunogen to stimulate host immune system and robust B-cell activation. We synthesized three peptides located at the conserved regions of N-protein among CoVs. One peptide showed as a good immunogen for vaccination as well. Cytokine arrays on post-vaccination mouse sera showed progressive up-regulation of various cytokines such as IFN-γ and CCL5, suggesting that TH1 associated responses are also stimulated. Furthermore, vaccinated mice exhibited an elevated memory T cells population. Here, we propose an unconventional vaccine strategy targeting the conserved N-protein as an alternative vaccine target for coronaviruses. Moreover, we generated a mouse monoclonal antibody specifically against an epitope shared between SARS-CoV and SARS-CoV-2, and we are currently developing the First-in-Class humanized anti-N-protein antibody to potentially treat patients infected by various CoVs in the future. SN - 1573-4935 UR - https://www.unboundmedicine.com/medline/citation/34519332/Targeting_intra_viral_conserved_nucleocapsid__N__proteins_as_novel_vaccines_against_SARS_CoVs_ L2 - https://portlandpress.com/bioscirep/article-lookup/doi/10.1042/BSR20211491 DB - PRIME DP - Unbound Medicine ER -