LIPOSOMAL S MUTANS DELIVERY SYSTEM FOR CARIES IMMUNITY

描述（改编自申请人摘要）：尽管有预防作用 虽然已经制定了一些措施，但龋齿仍然是一个主要的 全球性疾病。 虽然不是最具破坏性的，但这种传染性 疾病可能是发展中最普遍和最昂贵的疾病， 作为工业化国家。 分泌型伊加是第一道防线 抵抗通过口腔侵入的病原体，包括 变形链球菌（与龋齿引发相关的细菌）。 尽管在开发针对大肠杆菌的粘膜疫苗方面进行了广泛的努力， 微生物病原体，（例如，S.变种人），这种免疫途径仅 最近被认为是首选路线，相比之下， 常规全身途径诱导保护性免疫。 最近 初步的人类免疫研究一致发现唾液 S-IgA应答当口服脂质体抗原时的变异体; 然而，唾液反应的强度低且持续时间短。 为了改善唾液对唾液酸的反应的程度和持久性， 粘膜脂质体疫苗、两种新的免疫途径和佐剂 将在本提案中进行调查。 具体而言，拟议的研究 将决定三种含有S. 变形葡糖基转移酶（霍乱毒素B亚单位[CT B]-脂质体， 单磷酰脂质A [MPL]-脂质体，常规脂质体）诱导 经胃、鼻或局部给药时的口腔粘膜反应 路线在实验大鼠龋齿模型。 建议的结果 动物研究和先前的临床研究旨在 为人体方案的设计提供支持性证据和依据 旨在诱导针对S.变形菌疫苗 FDA I期研究。 在剂量反应研究之后，双盲FDA II期临床研究（包括实验组和对照组各100例 受试者）的免疫原性和有效性进行研究。 确定了最佳脂质体S。变形杆菌疫苗和途径 的目标 这项建议是确定一种针对沙门氏菌的“候选”疫苗。突变诱导的 龋病 有人建议，这些研究将提高设计 和龋齿疫苗的开发，以及 用于诱导保护性粘膜免疫的脂质体免疫策略 对各种其他病原体引起的疾病的反应。 预期上述 申请人认为，在免疫接种的有利鉴定之前， 一种新的防龋粘膜疫苗--给药途径和给药系统 完成后，将准备进行田间试验（FDA III期研究）， 这些研究。

DESCRIPTION (Adapted from the Applicant's Abstract): Despite preventive measures that have been developed, dental caries persists as a major worldwide disease. Although not the most devastating, this infectious disease may be the most prevalent and costly disease in developing, as well as industrialized countries. Secretory IgA is a first line of defense against pathogens that invade through the oral cavity, including Streptococcus mutans (the bacterium associated with caries initiation). Despite extensive efforts on the development of a mucosal vaccine against microbial pathogens, (e.g., S. mutans), this route of immunization is only recently being recognized as the preferred route, compared to the conventional systemic route in inducing protective immunity. Recent preliminary human immunization studies have consistently found salivary S-IgA responses to S. mutans when liposomal antigens are given orally; however, the salivary responses were of low magnitude and short duration. In order to improve the magnitude and persistence of salivary responses to the mucosal liposomal vaccine, two new routes of immunization and adjuvants will be investigated in this proposal. Specifically, the proposed studies will determine the effectiveness of three liposome vaccines containing S. mutans glucosyltransferase (Cholera toxin B subunit [CTB]-Liposomes, monophosphoryl lipid A [MPL]-Liposomes, Conventional Liposomes) to induce oral mucosal responses when administered by gastric, nasal, or topical routes in an experimental rat caries model. The results of the proposed animal studies, and those of previous clinical studies, are intended to provide supporting evidence and rationale for the design of human protocols aimed at inducing potential salivary immune responses to S. mutans vaccines by FDA Phase I studies. Following a dose response study, a double blind FDA Phase II clinical study (involving experimental and control groups of 100 subjects) is proposed to study the immunogenicity and efficacy of the identified optimal liposomal S. mutans vaccine and route. The objective of this proposal is to identify a "candidate" vaccine against S. mutans-induced dental caries. It is suggested that these studies will enhance the design and development of a dental caries vaccine, as well as liposomal-immunization strategies for use in inducing protective mucosal responses to various other pathogen-induced diseases. It is anticipated by the applicants that, pending favorable identification of an immunization route and delivery system, a candidate mucosal vaccine against dental caries will be ready for field trials (FDA Phase III studies) upon completion of these studies.