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_ DB - PRIME DP - Unbound Medicine ER -