Development of a rapidly scalable vaccine is still an urgent task to halt the spread of COVID-19. We have demonstrated biodegradable mesoporous silica nanoparticles (BMSNs) as a good drug delivery carrier for tumor therapy. In this study, seven linear B cell epitopes and three CD8+ T cell epitopes were screened from the spike (S) glycoprotein of SARS-CoV-2 by computer-based immunoinformatic approaches for vaccine design. A nanoparticle-based candidate vaccine (B/T@BMSNs) against SARS-CoV-2 was rapidly prepared by encapsulating these ten epitope peptides within BMSNs, respectively. BMSNs with potential biodegradability, proved to possess excellent safety in vitro and in vivo, could efficiently deliver epitope peptides into the cytoplasm of RAW264.7 cells. Strong Th1-biased humoral and cellular immunity were induced by B/T@BMSNs in mice and all the 10 selected epitopes were identified as effective antigen epitopes, which could induce robust peptide-specific immune response. The elicited functional antibody could bind to the recombinant S protein and block the binding of the S protein to the ACE-2 receptor. These results demonstrate the potential of a nanoparticles vaccine platform based on BMSNs to rapidly develop peptide-based subunit vaccine candidates against SARS-CoV-2.