Development of transcutaneous vaccine for prevention of periodontal diseases

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(40k-OMP)经鼻或经皮接种疫苗诱导免疫应答的潜力，以保护宿主免受攻击。经皮免疫40K-OMP可引起血清和唾液中的IgA抗体(Ab)反应，抑制皮下注射牙龈假单胞菌的脓肿形成。此外，40k-OMP鼻腔免疫和结合突变霍乱毒素A亚基和大肠杆菌不耐热肠毒素B亚基的无毒嵌合佐剂(MCTA/LTB)可诱导长期的40k-OMP特异性血清和唾液抗40k-OMP抗体应答。虽然MCTA/LTB在唾液中产生与CT相似的抗体应答，但MCTA/LTB诱导的总IgE和40k-OMP特异性IgE抗体以及IL-4水平均低于CT。重要的是，给予鼻腔40k-OMP加MCTA/LTB的小鼠Sho…免疫后1年，因口腔感染牙周炎引起的牙槽骨丢失明显减少。这些结果表明，40k-OMP联合MCTA/LTB是一种有效的人类牙龈假单胞菌感染疫苗。在下一项研究中，我们评估了一种针对牙龈假单胞菌感染的鼻用疫苗预防动脉硬化的效果。用40k-OMP加CT鼻腔免疫载脂蛋白E缺陷型自发性高脂血症(APOE、SHL&GT；)小鼠，然后用牙周炎螺旋体(P.gigivalis)进行攻击。APOE&lt；shl&gt；感染牙周炎小鼠的主动脉窦被斑块覆盖面积增加，血清IL-8水平升高。相比之下，40k-OMP+CT鼻腔免疫显著减少了动脉窦内动脉粥样硬化斑块的积聚和IL-8的反应。提示牙龈假单胞菌感染可加速动脉粥样硬化，鼻腔注射40k-OMP可能对减轻牙龈假单胞菌所致动脉粥样硬化有效。较少

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