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Anti-atherosclerotic vaccination against Porphyromonas gingivalis as a potential comparator of statin in mice

 Hyun-Su Ha  ;  Tae Young Kim  ;  Soo Jung Han  ;  Hak-Joon Sung  ;  Kyoung Yul Seo  ;  Jong-Won Ha 
 PEERJ, Vol.9 : e11293, 2021-04 
Journal Title
Issue Date
Atherosclerosis ; Mucosal immunization ; Periodontitis ; Periodontopathic bacteria ; Porphyromonas gingivalis ; Statin ; Vaccination
Background: Porphyromonas gingivalis (Pg) is an oral anaerobe which damages teeth and periodontal tissues. Its body infection is known to cause chronic inflammation, thereby inducing an early stage of atherosclerosis through humoral immune actions. Hence, vaccination by immunizing the proteins of P. gingivalis (Pg) post sonication with heating may prevent atherosclerosis. This study aimed to compare the effect of its vaccination with statin, which effectively prevents atherosclerosis by lowering lipids.

Methods: The vaccine was produced by sonicating P. gingivalis through heating, and a total of 32 male APOE-/-mice (8-week old) were subjected Western diet for 8 weeks, in order to induce atherosclerosis in a physiological manner. Then, the mice were grouped to undergo four treatment conditions (i.e., no treatment, pitavastatin, vaccine, or pitavastatin with vaccine). Vaccination was conducted through nasal immunization and confirmed by a Pg-specific humoral immune reaction. Then, half of the mice in each group were orally injected with P. gingivalis for the next 5 weeks while the other half remained uninfected, generating a total of eight groups (n = 4/group). The mice were sacrificed at 3 weeks after the last injection. After harvesting the aorta, Oil Red O staining of en face was conducted with imaging and image analysis, and plaque formation was quantitatively determined.

Results: Compared to no treatment, the vaccination through nasal immunization significantly reduced the atherosclerotic plaque sizes in APOE -/- mice under Western diet to the comparable level of statin group. When both vaccine and statin were used, no clear synergistic effect was observed as opposed to expectation.

Conclusions: This study revealed that nasal immunization of heat shock P. gingivalis has a significant impact on the prevention of arteriosclerosis and acts as a potential comparator of statin.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Seo, Kyoung Yul(서경률) ORCID logo https://orcid.org/0000-0002-9855-1980
Sung, Hak-Joon(성학준) ORCID logo https://orcid.org/0000-0003-2312-2484
Ha, Jong Won(하종원) ORCID logo https://orcid.org/0000-0002-8260-2958
Ha, Hyun-Su(하현수)
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