Nasal immunization with Porphyromonas gingivalis outer membrane protein decreases P. gingivalis-induced atherosclerosis and inflammation in spontaneously hyperlipidemic mice

Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Chiba, Japan; Department of Intestinal Medicine, Nihon University School of Dentistry at Matsudo, Chiba, Japan

^* To whom correspondence should be addressed. Email: ochiai.tomoko{at}nihon-u.ac.jp.

	Abstract

Porphyromonas gingivalis has been shown to accelerate atherosclerotic lesion development in hyperlipidemic animals. We assessed the potential of a nasal vaccine against P. gingivalis infection for the prevention of 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 intravenously with P. gingivalis strain 381. The animals were euthanized 11 or 14 weeks later. Atheromatous lesions in the proximal aorta of each animal were analyzed histomorphometrically, and the serum concentrations of 40k-OMP-specific antibodies and cytokines were determined. The areas of the aortic sinus that were covered with atherosclerotic plaque and the serum levels of inflammatory cytokines and chemokines were increased in Apoe^shl mice challenged with P. gingivalis compared to non-challenged mice. In comparison, nasal immunization with 40k-OMP plus CT significantly reduced atherosclerotic plaque accumulation in the aortic sinus and lowered the serum levels of cytokines and chemokines compared to non-immunized animals. Nasal immunization also induced 40k-OMP-specific serum IgG and saliva IgA antibody responses. These findings suggest that systemic infection with P. gingivalis accelerates atherosclerosis in Apoe^shl mice, and 40k-OMP plus CT may be an effective nasal vaccine for the reduction of atherosclerosis accelerated by P. gingivalis in the hyperlipidemic mouse model.