Intranasal MyD88-adjuvanted DNA vaccine against P. gingivalis in rat periodontitis

BACKGROUND: Periodontitis is a prevalent chronic inflammatory disease characterized by progressive destruction of periodontal supporting tissues. Although DNA vaccines targeting periodontal pathogens have shown potential, insufficient immunogenicity remains a major limitation. METHODS: A MyD88-adjuvanted DNA vaccine targeting Porphyromonas gingivalis antigens was developed and administered intranasally in a rat model of periodontitis. Rats were randomly assigned to five groups (n = 3–7 per group). Vaccine‑induced immune responses, alveolar bone loss, and safety were systematically evaluated. RESULTS: Intranasal immunization with the MyD88-adjuvanted vaccine elicited significantly enhanced mucosal and systemic antibody responses, including elevated salivary secretory IgA and serum antigen‑specific IgG and IgA. The vaccine promoted coordinated activation of B cells and follicular helper T cells in mucosal and systemic lymphoid tissues. Importantly, vaccinated rats exhibited markedly reduced alveolar bone loss compared with disease controls and the non‑adjuvanted vaccine group. Quantitatively, intranasal MyD88-adjuvanted vaccination significantly decreased alveolar bone loss (one-way ANOVA, F(4,10) = 137.1, P < 0.05). The mean bone loss was reduced from approximately 0.78 mm in the periodontitis group to approximately 0.56 mm in the MyD88-adjuvanted group. No significant adverse effects or pathological changes were observed. CONCLUSIONS: These findings indicate that MyD88 effectively enhances the immunogenicity and protective efficacy of a periodontal DNA vaccine. This intranasal MyD88-adjuvanted DNA vaccine may be useful as a preventive and adjunctive immunotherapeutic strategy and warrants further translational studies in oral health.