GPTMS–chitosan–modified dendritic mesoporous silica nanoadjuvants synergistically enhance humoral and cellular immune responses

Functionalized dendritic MSNs with uniform size and good biocompatibility were synthesized as vaccine adjuvants. • MSN-GPTMS-CS elicits strong humoral (IgM, IgG1, IgG2b) and elevated IgG2a (cellular immunity). • MSN-GPTMS-CS overcomes aluminum adjuvant limit by eliciting coordinated humoral/cellular responses without systemic toxicity. Vaccine adjuvants are critical for enhancing immune responses. Although aluminum-based adjuvants are widely used in clinical practice and can improve immunogenicity, they exhibit significant limitations, including limited immunostimulatory capacity and difficulty in precisely controlling response quality. They primarily induce humoral immunity, show limited ability to activate cellular immunity, and are associated with potential risks of cumulative neurotoxicity. In this study, dendritic mesoporous silica nanoparticles (MSN) with uniform particle size were synthesized and subsequently functionalized with amino groups, epoxy groups, or epoxy–chitosan to generate the adjuvant systems MSN-APTES, MSN-GPTMS, and MSN-GPTMS-CS, respectively. All adjuvant formulations exhibited well-controlled physicochemical properties and favorable biocompatibility. Using ovalbumin (OVA) as a model antigen, the adjuvant activities of MSN, MSN-APTES, MSN-GPTMS, and MSN-GPTMS-CS were evaluated in mice. MSN-GPTMS-CS induced a strong IgM response by day 14 and significantly increased IgG1, IgG2a, and IgG2b titers by day 28, with humoral immunity comparable to that induced by aluminum adjuvants. The elevated IgG2a levels suggest effective activation of cellular immunity, indicating concurrent humoral and cellular immune responses, and no obvious systemic toxicity was observed. Collectively, MSN-GPTMS-CS represents a promising strategy capable of simultaneously eliciting potent humoral and cellular immune responses, thereby providing a foundation for the development of engineered adjuvant-based vaccines that induce coordinated immune activation.