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。多项研究表明，该菌产生的半胱氨酸蛋白酶(牙龈痛)在牙周病中起重要作用。最近，一些研究表明，用牙龈痛或这些牙龈痛的部分免疫小鼠，可以保护它们免受牙龈假单胞菌的攻击。由于牙龈假单胞菌的感染始于牙周袋，我们认为将牙龈痛输送到粘膜表面是试图预防牙龈假单胞菌引起的疾病的一种新方法。减毒鼠伤寒沙门氏菌口服免疫已被证明是增强粘膜表面宿主免疫应答的有效途径。我们建议构建表达牙痛区域特异性/LT-B(大肠杆菌不耐热肠毒素结合域)融合的减毒鼠伤寒沙门氏菌。这些沙门氏菌菌株的口服免疫能力将在一只小鼠-P。牙周炎口腔感染模型。这些数据将为深入了解粘膜免疫策略预防牙龈假单胞菌引起的疾病的有效性提供依据，并开始鉴定哪些牙龈痛特异性表位介导了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.