Targeting intra-viral conserved nucleocapsid (N) proteins as novel vaccines against SARS-CoVs
| العنوان: | Targeting intra-viral conserved nucleocapsid (N) proteins as novel vaccines against SARS-CoVs |
|---|---|
| المؤلفون: | Qi Zeng, Cheng William Hong, Min Thura, Jie Li, Jimmy Hong, Abhishek Gupta, Joel Sng, Koon Hwee Ang |
| المصدر: | Bioscience Reports |
| بيانات النشر: | Portland Press Ltd., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Immunogen, COVID-19 Vaccines, viruses, Biophysics, Biology, medicine.disease_cause, Antibodies, Viral, Biochemistry, Virus, Epitope, Antibodies, Monoclonal, Murine-Derived, Epitopes, Mice, Immune system, Immunogenicity, Vaccine, Immunity, Virology, medicine, Animals, Coronavirus Nucleocapsid Proteins, Humans, Molecular Biology, Pandemics, Research Articles, Coronavirus, Immune Evasion, Nucleocapsid protein, Sequence Homology, Amino Acid, SARS-CoV-2, Pharmacology & Toxicology, COVID-19, Cell Biology, Th1 Cells, Vaccination, Severe acute respiratory syndrome-related coronavirus, Models, Animal, Spike Glycoprotein, Coronavirus, Vaccines, Subunit, biology.protein, Antibody, Vaccine |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1573-4935 0144-8463 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3adb1043016606fc3aa9a94218946e6f http://europepmc.org/articles/PMC8463655 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3adb1043016606fc3aa9a94218946e6f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15734935 01448463 |
|---|