Nasal immunization with a 40-kDa Outer Membrane Protein of Porphyromonas gingivalis Inhibits Atherosclerotic Plaque Accumulation Caused by Oral P. gingivalis Infection

Abstract

In this study, we assessed the potential of a nasal vaccine against oral Porphyromonas gingivalis infection for the prevention of P. gingivalis-accelerated atherosclerosis. Apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe^shl) mice were nasally immunized with the 40-kDa outer membrane protein (40k-OMP) of P. gingivalis plus cholera toxin (CT) as adjuvant and then challenged orally with P. gingivalis. Atheromatous lesions in the proximal aorta of each animal were analyzed histomorphometrically and the serum concentrations of 40k-OMP-specific antibodies were examined. Oral infection of Apoe^shl mice with P. gingivalis resulted in increased alveolar bone loss. Furthermore, the areas of the aortic sinus that were covered with atherosclerotic plaque were increased in those infected mice when compared with non-infected, control mice. However, nasal immunization of Apoe^shl mice with 40k-OMP plus CT as adjuvant induced significant levels of 40k-OMP-specific serum IgG and salivary IgA antibody responses. Interestingly, when Apoe^shl mice were nasally immunized with 40k-OMP plus CT before the infection, alveolar bone loss as along with atherosclerotic plaque accumulation in the aortic sinus were significantly reduced. These results suggest that oral infection with P. gingivalis accelerates atherosclerosis in Apoe^shl mice and that 40k-OMP plus CT may be an effective nasal vaccine for the prevention of atherosclerosis accelerated by P. gingivalis infection.