A microscale vaccine containing SiO2 nanoparticles loaded in CaCO3 microparticles was constructed using the co-precipitation method.The antigen ovalbumin(OVA)was covalently conjugated with SiO2 nanopar-ticles,and these nanoparticles and CpG were co-encapsulated into CaCO3 microparticles,generating a vaccine with a size of approximately 5.2 μm.Scanning electron microscopy(SEM),energy-dispersive X-ray(EDX),elemental mapping,and Fourier transform infrared(FTIR)analyses confirmed the successful preparation of the microscale vaccine;the vaccine had good storage stability without sustained anti-gen release,and negligible cytotoxicity to dendritic cells(DCs)and macrophages.Compared to SiO2 nanoparticles,the microscale vaccine can significantly improve antigen/adjuvant uptake.DCs internal-ized the entire microscale vaccine into lysosomes via macropinocytosis,and an increase in antigen endo/lysosomal escape was observed by confocal laser scanning microscopy(CLSM).Specifically,DCs pulsed with the vaccine were fully mature,expressing high levels of costimulatory molecules(CD40,CD80,and CD86),MHCII,and MHCI and secreting high levels of proinflammatory cytokines(IL-12,TNF-α,IL-1 β,and IL-6).In addition,the vaccine had good in vivo biocompatibility,could protect the antigen from rapid degradation,and increased the retention time in lymph nodes.SiO2 nanoparticles-in-CaCO3 microparticles were an excellent carrier for antigen and adjuvant delivery.Hopefully,this study can provide some information on the design of microscale carriers for vaccine delivery systems.