Size-Dependent Multi-epitope Nanovaccines Based on Cationic Mesoporous Silica for Enhanced Immune Responses in Bacterial Infections

Vaccination represents a viable alternative to antibiotics for the treatment of drug-resistant bacterial infections. Nanovaccines utilize nanomaterials for antigen delivery, enhancing antigen stability, improving targeting efficiency, and potentiating immune responses. The capacity of nanovaccines to activate immune responses is constrained by various factors, including morphology, zeta potential, and particle size. In this study, bacterial cytoplasmic antigens (BC) were loaded into the pores of cationic mesoporous silica (MSNs) via electrostatic adsorption to obtain MSNs-BC, and bacterial membrane antigens (BM) were encapsulated on the surface of MSNs-BC through physical extrusion, resulting in the preparation of a multiepitope nanovaccine delivery platform (MSNs-BC@BM). Utilizing Staphylococcus aureus (S. aureus) as a model pathogen, the inner core size of the MSNs was adjusted to control the size of the MSNs-BC@BM. The antigen presentation and immunostimulatory capabilities of MSNs-BC@BM were systematically investigated within the particle size range of 10–200 nm. The study findings revealed that the medium-sized nanovaccine of MSNs-BC@BM (MMSNs-BC@BM) with a particle size of approximately 90 nm demonstrated significantly enhanced humoral and cellular immune activation capabilities both in vitro and in vivo. In a murine model of S. aureus wound infection, immunization with MMSNs-BC@BM significantly reduced bacterial burden, facilitated wound healing, and alleviated inflammatory responses. The research findings reveal the size-dependent orchestration of immune responses of MSNs-based comprehensive antigen nanovaccines, providing insights into the rational design and development of effective antibacterial vaccines.