Development of transcutaneous vaccine for prevention of periodontal diseases

开发预防牙周病的经皮疫苗

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592270/
• 关键词: 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

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，我们评估了使用牙龈卟啉单胞菌 (40k-OMP) 产生的 40-kDa 外膜蛋白的鼻内或经皮疫苗诱导免疫反应以保护宿主免受 40k-OMP 攻击的潜力。皮下注射牙龈卟啉单胞菌引起显着的血清和唾液 IgA 抗体 (Ab) 反应，抑制脓肿形成。此外，鼻腔免疫。含有 40k-OMP 和无毒嵌合佐剂，该佐剂将突变型霍乱毒素的 A 亚基与大肠杆菌 (mCTA/LTB) 不耐热肠毒素的 B 亚基结合在一起，诱导长期 40k-OMP 特异性血清和唾液抗 40k -OMP Ab 反应 虽然使用 mCTA/LTB 在唾液中产生与使用 CT 作为佐剂相当的 Ab 反应，但总 IgE 和mCTA/LTB 诱导的 40k-OMP 特异性 IgE 抗体以及 IL-4 水平低于 CT 诱导的水平。重要的是，经鼻注射 40k-OMP 加 mCTA/LTB 的小鼠牙槽骨显着减少。即使在免疫接种一年后，口腔感染牙龈卟啉单胞菌也会造成损失。这些研究结果表明，鼻腔施用 40k-OMP 加 mCTA/LTB 应该是一种有效的方法。人类对抗牙龈卟啉单胞菌感染的有效疫苗在下一项研究中，我们对载脂蛋白 E 缺陷型自发性高脂血症 (Apoe^shl>) 小鼠进行鼻腔疫苗接种，以评估其预防动脉粥样硬化的功效。用 40k-OMP 加 CT 免疫，然后用牙龈卟啉单胞菌静脉注射攻击覆盖有动脉粥样硬化斑块的主动脉窦区域。并且用牙龈卟啉单胞菌攻击的Apoe^<shl>小鼠的血清IL-8水平增加。相比之下，用40k-OMP加CT的鼻部免疫显着减少了主动脉窦中的动脉粥样硬化斑块积聚和IL-8反应。这些结果表明，牙龈卟啉单胞菌感染会加速动脉粥样硬化，鼻腔40k-OMP可能可以有效减少牙龈卟啉单胞菌加速的动脉粥样硬化。较少的

项目成果

Nasal immunization with a 40-kDa Outer Membrane Protein of Porphyromonas gingivalis Inhibits Atherosclerotic Plaque Accumulation Caused by Oral P.ginggivalis Infection

使用 40 kDa 牙龈卟啉单胞菌外膜蛋白进行鼻免疫可抑制口腔牙龈卟啉单胞菌感染引起的动脉粥样硬化斑块积聚

• 发表时间: 2008
• 期刊: Int.J.Oral-Med.Sci. 6
• 作者: 島津 篤;河原和子;T. Hashizume;Y. Koizumi
• 通讯作者: Y. Koizumi

A nontoxic adjuvant for oral immunity to outer membrane protein of Porphyromonas gingivalis

牙龈卟啉单胞菌外膜蛋白口腔免疫无毒佐剂

• 发表时间: 2006
• 作者: 長岡正博;田谷かほる;浜田節男他;T. Hashizume;F. Momoi
• 通讯作者: F. Momoi

歯周病細菌タンパク抗原を発現する乳酸菌による特異的体応答の誘導

表达牙周病细菌蛋白抗原的乳酸菌诱导特异性身体反应

• 发表时间: 2007
• 作者: Taihei;Yamaguchi;Takahiko;Oho;F. Momoi;田中 宏征
• 通讯作者: 田中 宏征

Suppression of inflammatory cytokine production and induction of apoptosis in periodontal pathogen sensitized HUVEC cells

抑制牙周病原菌致敏的 HUVEC 细胞炎症细胞因子的产生并诱导细胞凋亡

• 发表时间: 2007
• 作者: Miyake T;Kambara M;et al.;Y. Koizumi
• 通讯作者: Y. Koizumi

CpG oligodeoxynucleotide is an effective adjuvant for transcutaneous immunization

CpG 寡脱氧核苷酸是经皮免疫的有效佐剂

• 发表时间: 2007
• 期刊: Int.J.Oral-Med.Sci. 6
• 作者: Momoi;F.;Hashizume;T.;Kurita-Ochiai;T.;Yuki;Y.;Kiyono;H.;Yamamoto;M;Y. Koizumi;山口 泰平・於保 孝彦;T. Hashizume;Chen Lu Liu
• 通讯作者: Chen Lu Liu