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https://doi.org/10.1042/bsr20211491
Title: | Targeting intra-viral conserved nucleocapsid (N) proteins as novel vaccines against SARS-CoVs | Authors: | Thura, Min En Sng, Joel Xuan Ang, Koon Hwee Li, Jie Gupta, Abhishek Hong, Jimmy Ming Hong, Cheng William Zeng, Qi |
Issue Date: | 14-Sep-2021 | Publisher: | Portland Press Ltd | Citation: | Thura, Min, En Sng, Joel Xuan, Ang, Koon Hwee, Li, Jie, Gupta, Abhishek, Hong, Jimmy Ming, Hong, Cheng William, Zeng, Qi (2021-09-14). Targeting intra-viral conserved nucleocapsid (N) proteins as novel vaccines against SARS-CoVs. Bioscience Reports 41 (9) : BSR20211491. ScholarBank@NUS Repository. https://doi.org/10.1042/bsr20211491 | Rights: | Attribution 4.0 International | 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-? 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. © 2021 The Author(s). | Source Title: | Bioscience Reports | URI: | https://scholarbank.nus.edu.sg/handle/10635/233129 | ISSN: | 0144-8463 | DOI: | 10.1042/bsr20211491 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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