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Infection and Immunity, July 2008, p. 2958-2965, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.01572-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

Y. Koizumi,1 T. Kurita-Ochiai,1* S. Oguchi,2 and M. Yamamoto1

Department of Microbiology and Immunology,1 Department of Internal Medicine, Nihon University School of Dentistry at Matsudo, Chiba, Japan2

Received 28 November 2007/ Returned for modification 27 December 2007/ Accepted 9 April 2008

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 (Apoeshl) 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 Apoeshl 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 Apoeshl 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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-nishi, Matsudo-shi, Chiba 271-8587, Japan. Phone: 81 (47) 360-9432. Fax: 81 (47) 360-9601. E-mail: ochiai.tomoko{at}nihon-u.ac.jp

{triangledown} Published ahead of print on 21 April 2008.

Editor: R. P. Morrison

Infection and Immunity, July 2008, p. 2958-2965, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.01572-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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