Intranasal Vaccination of Recombinant Adeno-Associated Virus Encoding Receptor-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Spike Protein Induces Strong Mucosal Immune Responses and Provides Long-Term Protection against SARS-CoV Infection

摘要: We have previously reported that a subunit protein vaccine based on the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus (SARS-CoV) spike and recombinant adeno-associated virus (rAAV)-based RBD (RBD-rAAV) could induce highly potent neutralizing Ab responses in immunized animals. In this study, systemic, mucosal, cellular immune long-term protective immunity induced by RBD-rAAV were further characterized BALB/c mouse model, with comparison i.m. intranasal (i.n.) routes administration. Our results demonstrated that: 1) i.n. vaccination systemic humoral response comparable strength shorter duration than vaccination, but local was much stronger; 2) elicited stronger specific cytotoxic T cell as evidenced higher prevalence IL-2 and/or IFN-gamma-producing CD3+/CD8+ cells both lungs spleen; 3) similar protection against SARS-CoV challenge mice; 4) titers mucosal IgA serum-neutralizing associated lower viral load less pulmonary pathological damage, while no Ab-mediated disease enhancement effect observed; 5) provide infection. Taken together, our findings suggest can be developed into candidate for prevention SARS may preferred route administration due to its ability SARS-CoV-specific better safety profile.