LAUSR

Abstract A microscale vaccine that SiO2 nanoparticles-loaded in CaCO3 microparticles was constructed through the co-precipitation method, the antigen was covalently conjugated with SiO2 nanoparticles, then these nanoparticles and CpG were co-encapsulated into CaCO3 microparticles, generating the vaccine with a size of approximately 5.2 μm. SEM, EDX, element mapping, and FTIR confirmed the successful preparation of microscale vaccine, which had good storage stability without the sustained release of antigen, and negligible cytotoxicity to dendritic cells (DCs) and macrophages. Compared to SiO2 nanoparticles, the microscale vaccine can significantly improve the antigen/adjuvant uptake. DCs internalized the entire microscale vaccine into lysosome via macropinocytosis, and an increase in antigen endo/lysosomal escape was observed by CLSM. Specifically, DCs pulsed by the vaccine was fully mature, not only expressing high levels of costimulatory molecules (CD40, CD80, CD86), MHC II and MHC I, but also secreting high levels of pro-inflammatory cytokines (IL-12, TNF-α, IL-1β and IL-6). Besides, the vaccine had good in vivo biocompatibility, can protect the antigen from rapid degradation, and increase the retention time in lymph nodes (LNs). SiO2 nanoparticles-in-CaCO3 microparticles was an excellent carrier of antigen/adjuvant delivery. Hopefully, this work can provide some information on the design of microscale carrier for vaccine delivery system.