ORAL IMMUNIZATION WITH GINGIPAIN DELIVERED BY SALMONELLA

牙龈卟啉单胞菌是成人牙周病的重要病原体。多项研究表明，这种生物体产生的半胱氨酸蛋白酶（牙龈蛋白酶）在牙龈卟啉单胞菌诱发的牙周病中发挥着重要作用。 最近，一些研究表明，用牙龈蛋白酶或这些牙龈蛋白酶区域对小鼠进行免疫可以提供针对随后的牙龈卟啉单胞菌攻击的保护。由于牙龈卟啉单胞菌感染始于牙周袋，我们相信将牙龈蛋白酶递送至粘膜表面代表了尝试预防牙龈卟啉单胞菌引起的疾病的新方法。减毒鼠伤寒沙门氏菌口服免疫已被证明是增强宿主粘膜表面免疫反应的有效方法。我们建议构建表达牙龈蛋白酶区域特异性/LT-B（大肠杆菌不耐热肠毒素的结合域）融合体的减毒鼠伤寒沙门氏菌菌株。这些沙门氏菌菌株的口服免疫预防牙龈卟啉单胞菌介导的骨质流失的能力将在小鼠沙门氏菌中进行评估。牙龈炎口腔感染模型。这些数据将深入了解粘膜免疫策略在预防牙龈卟啉单胞菌引起的疾病方面的有用性，并开始表征哪些牙龈蛋白酶特异性表位介导这种保护性宿主免疫反应。

Porphyromonas gingivalis is an important pathogen in adult periodontal disease. Several studies have suggested that the cysteine-proteases (gingipains) produced by this organism play an important role during P. gingivalis-induced periodontal disease. Recently, several investigations indicate that immunization of mice with gingipains or regions of these gingipains provide protection from subsequent P. gingivalis challenge. As, P. gingivalis infection begins in the periodontal pocket, we believe that delivery of gingipains to mucosal surfaces represents a novel approach to attempt to prevent P. gingivalis-induced disease. Oral immunization with attenuated Salmonella typhimurium has been demonstrated to be an effective way to enhance the host immune response at mucosal surfaces. We propose to construct attenuated S. typhimurium strains expressing gingipain region-specific/LT-B (binding domain of E. coli heat-labile enterotoxin) fusions. The ability of oral immunization of these Salmonella strains to protect against P. gingivalis-mediated bone loss will be evaluated m a mouse-P. gingivalis oral infection model. These data will provide insight into the usefulness of mucosal immunization strategies to prevent P. gingivalis-induced disease and begin the process of characterizing which gingipain-specific epitopes mediate this protective host immune response.