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Development of transcutaneous vaccine for prevention of periodontal diseases

开发预防牙周病的经皮疫苗

基本信息

批准号：
18592270
负责人：
YAMAMOTO Masafumi
金额：
$ 2.5万
依托单位：
Nihon University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

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 … More 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

在这项研究中，我们已经评估了使用牙龈卟啉单胞菌（40 k-OMP）产生的40 kDa外膜蛋白的鼻内或经皮疫苗诱导免疫应答的潜力，该免疫应答将保护宿主免受攻击。40 k-OMP经皮免疫引起显著的血清和唾液伊加抗体（Ab）应答，其抑制皮下注射牙龈卟啉单胞菌的脓肿形成。此外，用40 k-OMP和将突变霍乱毒素的A亚单位与来自大肠杆菌的不耐热肠毒素的B亚单位（mCTA/LTB）组合的无毒嵌合佐剂鼻免疫诱导长期的40 k-OMP特异性血清和唾液抗40 k-OMP Ab应答。虽然使用mCTA/LTB在唾液中产生与使用CT作为佐剂相当的Ab应答，但由mCTA/LTB诱导的总IgE和40 k-OMP特异性IgE Ab以及IL-4水平低于由CT诱导的水平。重要的是，鼻内给予40 k-OMP + mCTA/LTB的小鼠， ...更多信息免疫后一年，牙龈卟啉单胞菌口腔感染引起的牙槽骨丢失显著减少。这些发现表明，鼻内施用40 k-OMP加mCTA/LTB应该是人类对抗牙龈卟啉单胞菌感染的有效疫苗。在接下来的研究中，我们评估了针对牙龈卟啉单胞菌感染的鼻用疫苗预防动脉粥样硬化的功效。用40 k-OMP加CT经鼻免疫载脂蛋白E缺陷型自发性高脂血症（ApoE）小鼠，然后用牙龈卟啉单胞菌静脉内攻击。在用牙龈卟啉单胞菌攻击的ApoE^小鼠中，主动脉窦被动脉粥样硬化斑块覆盖的面积和血清IL-8水平增加<shl>。相比之下，用40 k-OMP加CT的鼻免疫显著降低了主动脉窦中的动脉粥样硬化斑块积聚和IL-8应答。提示牙龈卟啉单胞菌感染可加速动脉粥样硬化的发生，鼻用40 k-OMP可能对减轻牙龈卟啉单胞菌引起的动脉粥样硬化有一定作用。少