High immunogenicity of a new mucosal vaccine against Porphyromonas gingivalis

Porphyromonas gingivalis (P. gingivalis) is a keystone pathogen in chronic periodontal disease, primarily colonizing the oral mucosa. Current therapeutic strategies are limited in efficacy, emphasizing the need for preventive vaccination approaches capable of eliciting both systemic and mucosal immunity. This study evaluated the immunogenicity of an intranasal protein-based vaccine targeting P. gingivalis . Mice were intranasally immunized twice with a multi-antigen vaccine composed of three key P. gingivalis proteins produced using a cell-free protein synthesis platform and adjuvanted with double-mutant heat-labile toxin. Two vaccine doses (low: 5 µg per antigen; and high: 10 µg per antigen) were tested. We found that vaccine elicited robust and functional systemic IgG and mucosal IgA responses. Higher dose did not further enhance humoral responses. Importantly, both doses induced strong antigen-specific IFNγ production and generated CD4 + and CD8 + tissue-resident memory T cells (CD69 + CD103 + ) in the lungs. These findings provide proof-of-concept that targeting P. gingivalis via mucosal immunization can generate systemic and mucosal immune responses with functional antibody activity, supporting further efficacy testing in P. gingivalis oral challenge models, offering a promising strategy to prevent colonization and reduce the risk of periodontal disease.