Targeting intra-viral conserved nucleocapsid (N) proteins as novel vaccines against SARS-CoVs
Thura, Min En Sng, Joel Xuan Ang, Koon Hwee Li, Jie Gupta, Abhishek Hong, Jimmy Ming Hong, Cheng William Zeng, Qi
Thura, Min
En Sng, Joel Xuan
Ang, Koon Hwee
Li, Jie
Gupta, Abhishek
Hong, Jimmy Ming
Hong, Cheng William
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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).
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Source Title
Bioscience Reports
Publisher
Portland Press Ltd
Series/Report No.
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Rights
Attribution 4.0 International
Date
2021-09-14
DOI
10.1042/bsr20211491
Type
Article