Abstract
The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants seriously threatens the efficacy of current coronavirus disease 2019 (COVID-19) vaccines. Therefore, there is an urgent need to develop next-generation vaccine platforms capable of counteracting current and prospective viral variants. In this study, we employed synthetic biology technology to develop self-adjuvant-effect biomimetic nanovaccines with broad-spectrum capabilities for the prevention of SARS-CoV-2 infection. The biomimetic nanovaccines prepared by loading the SARS-CoV-2 RBD protein into dendritic mesoporous organosilicon nanoparticles (DMOSN) significantly promote the recruitment of dendritic cells (DCs) to secondary lymphoid organs, thereby initiating antibody-dependent humoral immune responses mediated by follicle helper T (Tfh) cells, germinal center (GC) B cells, and plasma cells. Moreover, DMOSN@RBD induced not only potent humoral immunity but also Th2-biased cellular immunity along with robust Th1-type cellular immune responses, which are pivotal in restricting SARS-CoV-2 infection. Our work provides a simple and environmentally friendly strategy for synthesizing nanovaccines with significant immunostimulatory potential, offering novel insights for the future development of durable and effective antiviral broad-spectrum nanovaccines.IMPORTANCEThe persistent evolution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) underscores the critical need to continually assess vaccine immunogenicity and protective efficacy against emerging variants in preclinical animal models. Our study demonstrates that biomimetic nanoparticle vaccines elicit more durable antibody responses and enhanced T cell responses compared to conventional aluminum hydroxide-adjuvanted formulations. Notably, RBD antigen-decorated dendritic mesoporous organosilica nanoparticles (DMOSN@RBD) exhibit broad-spectrum neutralization potential against multiple SARS-CoV-2 variants of concern (VOCs). These findings establish engineered mesoporous silica nanoparticles as a potent immunostimulatory platform capable of simultaneously enhancing both humoral and cellular immunity in subunit vaccine design, particularly through the induction of robust T cell responses typically challenging to achieve with protein-based vaccines.