SARS-CoV S protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infection

Abstract

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