Oral immunization with Porphyromonas gingivalis outer membrane protein and CpG oligodeoxynucleotides attenuates P. gingivalis-accelerated atherosclerosis and inflammation

Abstract

ObjectiveIt has previously been shown that oral immunization with the 40-kDa outer membrane protein of Porphyromonas gingivalis (40k-OMP) and CpG oligodeoxynucleotides (ODN) as an adjuvant elicits protective antibody responses against alveolar bone loss caused by P. gingivalis infection. The objective of the present work was to assess the efficacy of this same oral vaccine on prevention of P. gingivalis-accelerated atherosclerosis. MethodsApolipoprotein E-deficient spontaneously hyperlipidemic (Apoeshl) mice were orally immunized with 40k-OMP plus CpG ODN and subsequently challenged intravenously with P. gingivalis. The mice were euthanized 15 weeks later, and atheromatous lesions in the proximal aorta of each mouse were analyzed histomorphometrically. Serum concentrations of 40k-OMP-specific antibodies and cytokines as well as levels of proatherogenic factors in the aorta were determined. ResultsP. gingivalis challenge resulted in an increase in the areas of the aortic sinus covered with atherosclerotic plaque, as well as in the levels of high-sensitive C-reactive protein (hsCRP) and some cytokines and chemokines, when compared with sham-treated mice. In contrast, oral immunization with 40k-OMP plus CpG ODN induced 40k-OMP-specific serum IgG responses, and significantly reduced atherosclerotic plaque accumulation in the aortic sinus, along with hsCRP and the cytokine and chemokine levels. ConclusionsThese results suggest that oral administration of 40k-OMP plus CpG ODN may be an effective vaccine for the prevention of accelerated atherosclerosis caused by P. gingivalis infection.