ORAL IMMUNIZATION WITH GINGIPAIN DELIVERED BY SALMONELLA

牙龈卟啉单胞菌是成人牙周病的重要致病菌。一些研究表明，由该生物体产生的半胱氨酸蛋白酶（牙龈菌蛋白酶）在牙龈卟啉单胞菌诱导的牙周病中起重要作用。 最近，一些研究表明，用牙龈卟啉菌蛋白酶或这些牙龈卟啉菌蛋白酶的区域免疫小鼠提供了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开始于牙周袋，我们认为牙龈卟啉单胞菌蛋白酶递送至粘膜表面代表了尝试预防牙龈卟啉单胞菌诱导的疾病的新方法。减毒鼠伤寒沙门氏菌口服免疫已被证明是一种有效的方式，以提高在粘膜表面的宿主免疫应答。我们建议构造衰减S。表达牙龈菌蛋白酶区域特异性/LT-B（E.大肠杆菌不耐热肠毒素）融合体。将在小鼠-牙龈卟啉单胞菌口腔感染模型中评价这些沙门氏菌菌株的口服免疫保护免受牙龈卟啉单胞菌介导的骨丢失的能力。这些数据将提供深入了解粘膜免疫策略的有用性，以防止牙龈卟啉单胞菌诱导的疾病，并开始的过程中，牙龈卟啉菌蛋白酶特异性表位介导这种保护性的宿主免疫应答。

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.