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菌。几项研究表明，该菌产生的半胱氨酸蛋白酶（gingipains）在牙龈假单胞菌引起的牙周病中起重要作用。最近，一些研究表明，对患有牙龈疼痛或这些牙龈疼痛区域的小鼠进行免疫接种可以保护小鼠免受后续牙龈卟啉菌的攻击。由于牙龈卟啉卟啉感染始于牙周袋，我们相信将牙龈痛传递到粘膜表面代表了一种尝试预防牙龈卟啉卟啉引起的疾病的新方法。口服减毒鼠伤寒沙门菌免疫已被证明是增强粘膜表面宿主免疫反应的有效途径。我们提出构建表达牙龈蛋白酶区域特异性/LT-B（大肠杆菌热不稳定肠毒素结合域）融合物的减毒鼠伤寒杆菌菌株。这些沙门氏菌的口服免疫对牙龈假单胞菌介导的骨质流失的保护能力将在小鼠实验中进行评估。牙龈口腔感染模型。这些数据将提供深入了解粘膜免疫策略的有用性，以预防牙龈卟啉卟啉引起的疾病，并开始表征牙龈特异性表位介导这种保护性宿主免疫反应的过程。

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.