tetano
Editor, Senior Moderator
Biosci Rep
. 2021 Sep 14;BSR20211491.
doi: 10.1042/BSR20211491. Online ahead of print.
Targeting Intra-Viral Conserved Nucleocapsid (N) Proteins as Novel Vaccines against SARS-CoVs
Min Thura[SUP] 1 [/SUP], Joel Xuan En Sng[SUP] 1 [/SUP], Koon Hwee Ang[SUP] 1 [/SUP], Jie Li[SUP] 1 [/SUP], Abhishek Gupta[SUP] 1 [/SUP], Jimmy Ming Hong[SUP] 2 [/SUP], Cheng William Hong[SUP] 3 [/SUP], Qi Zeng[SUP] 1 [/SUP]
Affiliations
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 3 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 upregulation 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.
Keywords: Coronavirus; Nucleocapsid protein; Vaccine.
. 2021 Sep 14;BSR20211491.
doi: 10.1042/BSR20211491. Online ahead of print.
Targeting Intra-Viral Conserved Nucleocapsid (N) Proteins as Novel Vaccines against SARS-CoVs
Min Thura[SUP] 1 [/SUP], Joel Xuan En Sng[SUP] 1 [/SUP], Koon Hwee Ang[SUP] 1 [/SUP], Jie Li[SUP] 1 [/SUP], Abhishek Gupta[SUP] 1 [/SUP], Jimmy Ming Hong[SUP] 2 [/SUP], Cheng William Hong[SUP] 3 [/SUP], Qi Zeng[SUP] 1 [/SUP]
Affiliations
- PMID: 34519332
- DOI: 10.1042/BSR20211491
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 3 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 upregulation 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.
Keywords: Coronavirus; Nucleocapsid protein; Vaccine.