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Targeting intra-viral conserved nucleocapsid (N) proteins as novel vaccines against SARS-CoVs.
Thura, Min; Sng, Joel Xuan En; Ang, Koon Hwee; Li, Jie; Gupta, Abhishek; Hong, Jimmy Ming; Hong, Cheng William; Zeng, Qi.
  • Thura M; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.
  • Sng JXE; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.
  • Ang KH; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.
  • Li J; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.
  • Gupta A; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.
  • Hong JM; Lee Kong Chian School of Medicine, Singapore 308232.
  • Hong CW; Department of Radiology, University of California San Diego, San Diego, CA 92103, USA.
  • Zeng Q; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.
Biosci Rep ; 41(9)2021 09 30.
Article in English | MEDLINE | ID: covidwho-1915305
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Nucleocapsid Proteins / COVID-19 Vaccines / COVID-19 / Antibodies, Viral Topics: Long Covid / Vaccines Limits: Animals / Humans Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Nucleocapsid Proteins / COVID-19 Vaccines / COVID-19 / Antibodies, Viral Topics: Long Covid / Vaccines Limits: Animals / Humans Language: English Year: 2021 Document Type: Article