| Project/Area Number |
18592270
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Periodontal dentistry
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| Research Institution | Nihon University |
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Principal Investigator |
YAMAMOTO Masafumi Nihon University, Microbiology and Immunology, Professor (80210558)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,910,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | periodontal vaccine / nontoxic chimeric enterotoxin / intranasl immunization / transcutaneous immunization / P.gingivalis / outer membrane protein / atherosclerosis / 歯周病 / 経皮ワクチン / Porphyromonas gingivalis / 赤血球凝集活性 / アジュバント |
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| Research Abstract |
In this study, we have assessed the potential of intranasal or transcutaneous vaccine using 40-kDa outer membrane protein produced from Porphyromonas gingivalis (40k-OMP), to induce an immune response that would protect the host from challenge. Transcutaneous immunization with 40k-OMP elicited significant serum and salivary IgA antibody (Ab) responses that inhibited abscess formation by the subdcutaneously injected P. gingivalis. Furthermore, nasal immunization with 40k-OMP and a nontoxic chimeric adjuvant that combines the A subunit of mutant cholera toxin with the B subunit of heat-labile enterotoxin from Escherichia coli (mCTA/LTB) induced long-term 40k-OMP-specific serum and salivary anti-40k-OMP Ab response. Although using mCTA/LTB gave comparable Ab responses in the saliva as using CT as adjuvant, the total IgE and 40k-OMP-specific IgE Abs, as well as IL-4 levels induced by mCTA/LTB were lower than those induced by CT. Importantly, the mice given nasal 40k-OMP plus mCTA/LTB sho
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wed significant reduction of alveolar bone loss caused by oral infection with P. gingivalis even one year after the immunization. These findings suggest that nasal administration of 40k-OMP plus mCTA/LTB should be an effective vaccine for humans against P. gingivalis infection. In the next study, we have assessed the efficacy 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 40k-OMP plus CT and then challenged intravenously with P. gingivalis. The areas of the aortic sinus that were covered with atherosclerotic plaque and the serum levels of IL-8 were increased in Apoe^<shl> mice challenged with P. gingivalis. In comparison, nasal immunization with 40k-OMP plus CT significantly reduced atherosclerotic plaque accumulation in the aortic sinus and the IL-8 responses. These findings suggest that infection with P. gingivalis accelerates atherosclerosis, and nasal 40k-OMP may be effective for the reduction of atherosclerosis accelerated by P. gingivalis. Less
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