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Background Methods Results Conclusions Arg‐gingipain A (RgpA) is the primary virulence factor of Porphyromonas gingivalis and contains hemagglutinin adhesin (HA), which helps bacteria adhere to cells and proteins. Hemagglutinin's functional domains include cleaved adhesin (CA), which acts as a hemagglutination and hemoglobin‐binding actor. Here, we confirmed that the HA and CA genes are immunogenic, and using adjuvant chemokine to target dendritic cells (DCs) enhanced protective autoimmunity against P. gingivalis–induced periodontal disease.C57 mice were immunized prophylactically with pVAX1‐CA, pVAX1‐HA, pVAX1, and phosphate‐buffered saline (PBS) through intramuscular injection every 2 weeks for a total of three administrations before P. gingivalis–induced periodontitis. The DCs were analyzed using flow cytometry and ribonucleic acid sequencing (RNA‐seq) transcriptomic assays following transfection with CA lentivirus. The efficacy of the co‐delivered molecular adjuvant CA DNA vaccine was evaluated in vivo using flow cytometry, immunofluorescence techniques, and micro‐computed tomography.After the immunization, both the pVAX1‐CA and pVAX1‐HA groups exhibited significantly elevated P. gingivalis–specific IgG and IgG1, as well as a reduction in bone loss around periodontitis‐affected teeth, compared to the pVAX1 and PBS groups (p < 0.05). The expression of CA promoted the secretion of HLA, CD86, CD83, and DC‐specific intercellular adhesion molecule‐3‐grabbing non‐integrin (DC‐SIGN) in DCs. Furthermore, the RNA‐seq analysis revealed a significant increase in the chemokine (C–C motif) ligand 19 (p < 0.05). A notable elevation in the quantities of DCs co‐labeled with CD11c and major histocompatibility complex class II, along with an increase in interferon‐gamma (IFN‐γ) cells, was observed in the inguinal lymph nodes of mice subjected to CCL19‐CA immunization. This outcome effectively illustrated the preservation of peri‐implant bone mass in rats afflicted with P. gingivalis–induced peri‐implantitis (p < 0.05).The co‐administration of a CCL19‐conjugated CA DNA vaccine holds promise as an innovative and targeted immunization strategy against P. gingivalis–induced periodontitis and peri‐implantitis. [ABSTRACT FROM AUTHOR]