Intranasal Immunization with Porphyromonas gingivalis Outer Membrane Protein Inhibits P. gingivalis-induced Atherosclerosis in C57BL/6 Mice Fed a Hgh-fat Diet

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Recent epidemiological studies have shown that an association exists between periodontal disease and cardiovascular disease. We have previously reported that long-term Porphyromonas gingivalis-challenge accelerated atherosclerosis in normal C57/BL6 mice fed a high-fat diet (HFD). In this study, we assessed the potential of a nasal vaccine for the prevention of atherosclerosis promoted by P. gingivalis. Eight-week-old C57BL/6 mice were nasally immunized with the 40-kDa outer membrane protein of P. gingivalis (40k-OMP) alone or together with a cDNA vector plasmid encoding Flt3 ligand (pFL) as adjuvant and then challenged intravenously with P. gingivalis strain 33277 three times per week for 10 weeeks and sacrificed at 19 weeks of age. Atheromatous lesions in the proximal aorta of each animal were analyzed histomorphometrically, and serum concentrations of 40-kDa OMP-specific antibodies, cytokines and C-reactive protein (CRP) were determined. Nasal immunization with 40k-OMP or 40k-OMP plus pFL significantly induced 40k-OMP-specific serum immunoglobulin G antibody response and reduced atherosclerotic plaque accumulation in the aortic sinus and lowered the serum levels of CRP and cytokines compared to nonimmunized animals. These findings suggest that 40k-OMP may be an effective nasal vaccine for the reduction of atherosclerosis accelerated by P. gingivalis in normal C57BL/6 mice fed HFD.

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