Nasal Immunization with Porphyromonas gingivalis Outer Membrane Protein Decreases P. gingivalis -Induced Atherosclerosis and Inflammation in Spontaneously Hyperlipidemic Mice

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 (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 40-kDa 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 nonchallenged mice. In comparison, nasal immunization with 40-kDa OMP plus CT significantly reduced atherosclerotic plaque accumulation in the aortic sinus and lowered the serum levels of cytokines and chemokines compared to nonimmunized animals. Nasal immunization also induced 40-kDa OMP-specific serum immunoglobulin G (IgG) and saliva IgA antibody responses. These findings suggest that systemic infection with P. gingivalis accelerates atherosclerosis in Apoe shl mice, and 40-kDa OMP plus CT may be an effective nasal vaccine for the reduction of atherosclerosis accelerated by P. gingivalis in the hyperlipidemic mouse model.

Periodontal disease and risk of atherosclerotic coronary heart disease

“…12,13 This organism promotes platelet aggregation, 14 foam cell formation, 15 and the development of atheromas in experimental animal models. [16][17][18][19] The following issues are discussed in this review:…”

Nasal immunization with the 40-kDa outer membrane protein of Porphyromonas gingivalis plus cholera toxin induces protective immunity in aged mice

“…Moreover, in previous studies, we have demonstrated that nasal immunization with 40k-OMP plus cholera toxin (CT) or non-toxic chimeric enterotoxin (mCTA/LTB) elicited 40k-OMP-specific secretory immunoglobulin A (IgA) and IgG antibodies (Abs) in both saliva and serum, which inhibited the coaggregation activity of P. gingivalis, thus reducing alveolar bone loss (15)(16)(17)(18). Furthermore, when apolipoprotein E-deficient spontaneously hyperlipidemic mice were immunized intranasally with 40k-OMP plus CT before infection with P. gingivalis, atherosclerotic plaque deposition in the aortic sinus was significantly reduced (19). These studies suggest that 40k-OMP may be an effective vaccine antigen (Ag) for prevention of P. gingivalis infection.…”

Comparative Study of the Effect of Basal Diet Formulation, Dietary Fat and Cholesterol Levels on the Development of Aortic Atherosclerotic Lesions in B6.KOR-Apoeshl Mice

“…These studies led us to predict that there might be some differences in the effect of atherogenic diet on atherosclerosis susceptibility between congenic SHL mice and apoE-/-mice. A few nutritional studies utilizing these three lines of congenic SHL mice have been reported 13,14) . From these considerations, the present experiment was carried out to determine experimental period and the adequate atherogenic diet composition such as dietary level of cholesterol and different type of oils, and AIN basal diets to induce reasonable atherosclerotic lesions for nutritional atherosclerosis studies using B6.KOR-Apoe shl mice.…”