Priming with rAAV encoding RBD of SARS-CoV S protein and boosting with RBD-specific peptides for T cell epitopes increase T cell responses and provide protection against SRAS-CoV infection

Du, Lanying; Zhao, Guangyu; Lin, Yongping; Chan, Chris CS; He, Yuxian; Jiang, Shibo; Wu, Changyou; Jin, Dong-Yan; Yuen, Kwok-Yung; Zhou, Yusen; Zheng, Bo-Jian

Development of vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is crucial in the prevention of SARS reemergence. The receptor-binding domain (RBD) of SARS-CoV spike (S) protein is an important target in developing safe and effective SARS vaccines. Our previous study has demonstrated that vaccination with adeno-associated virus encoding RBD (RBD-rAAV) induces high titer of neutralizing antibodies. In this study, we further assessed the immune responses and protective effect of the immunization with RBD-rAAV prime/RBD-specific T cell peptide boost, as compared to those of vaccinations with RBD-rAAV and RBD-peptides alone. Our results indicated that RBD-rAAV prime/RBD-peptide boost induced similar Th1 and neutralizing antibody responses, but stronger Th2 and CTL responses than RBD-rAAV prime/boost. The resulting immune responses protected the vaccinated mice from subsequent SARS-CoV challenge, which was evidenced by lower level of viral replication in mouse lung tissues. However, no significant immune responses and protective effect were detected in mice vaccinated with RBD-peptides or blank AAV alone. Since T cell epitopes are highly conserved and boosting with peptides may induce the production of effector memory T cells, our results suggest that the vaccination protocol used may be ideal for providing effective, universal and long-term protection against SARS-CoV infection.