Liposomal Recombinant Vaccine and Caries Immunity

描述（由申请人提供）：粘膜免疫系统是抵抗病原体的重要第一道防线，病原体通过粘膜组织的定植或侵入引起疾病，包括各种儿童疾病，如龋齿。然而，对儿童粘膜免疫系统及其粘膜免疫后唾液免疫应答的能力知之甚少。婴儿口腔病原体变形链球菌（MS）的最初“感染窗口”发生在18-24个月大，此时乳牙正在萌出。有人提出，当易受影响的牙齿长出时，其他“窗口”会打开，恒牙因此，我们认为，在“处女”牙齿出现之前诱导对MS的唾液抗体应答可以消除MS在这些牙齿上的定植。（10-12岁）和学前班（5-6岁）儿童对由Agl/II和葡糖基转移酶（SBR-GLU）的免疫原性亚基组成的重组嵌合蛋白的应答来自酿脓链球菌在第一个目标中，在开始对儿童进行SBR-GLU研究之前，将进行成人I期研究。在成人中证明安全性和免疫原性后，将采用3 x 2 x 2改良析因设计比较两个年龄组儿童中免疫接种途径和给药系统的有效性。将在免疫接种前后的不同时间收集血清和唾液，并通过ELISA分析MS抗原的抗体活性。在第二个目标中，将收集臼齿的唾液和菌斑样本，以表征新萌出的臼齿上MS感染的建立。将评估龋齿、饮食、唾液伊加抗MS、唾液中MS水平和萌出牙齿的菌斑等因素与新萌出牙齿定植时间的相关性。第三个目的是确定儿童粘膜免疫对萌出时未萌出牙齿表面MS定植的影响（即，恒牙臼齿）。将在免疫接种后收集唾液、血清和菌斑样品，该免疫接种将与恒牙萌出的时间相对应，以确定MS定殖时间是否由于诱导的免疫应答而被取消。所获得的关于儿童粘膜免疫应答诱导机制的信息将对开发诱导粘膜免疫以预防包括龋齿和牙周病在内的感染性疾病的方法具有重要意义。

DESCRIPTION (provided by applicant): The mucosal immune system is an important first line of defense against pathogens that cause disease by colonization of or invasion through mucosal tissues, including a variety of childhood diseases such as Dental caries. Nevertheless, little is know about the mucosal immune system in children and their ability to respond with salivary immune responses following mucosal immunization. An initial "window of infectivity" for the oral pathogens mutans streptococci (MS) in infants occurs at 18-24 months of age, a time when primary molar teeth are erupting. It has been proposed that other "windows" open when susceptible teeth erupt, e.g., permanent molar teeth. Therefore, the induction of a salivary antibody response to MS prior to the emergence of a "virgin" tooth may abrogate the colonization of these teeth by MS. The Aims of this application are to determine the ability of preadolescent (age 10-12 years) and preschool (5-6 years of age) children to respond to a recombinant chimeric protein consisting of immunogenic subunits of Agl/ll and glucosyltransferase (SBR-GLU) from S. mutans following mucosal immunization and to determine if the response induced would abrogate the colonization of newly erupted molars by MS. In the first Aim, before beginning studies with SBR-GLU in children, a Phase I Study on adults will be done. Following demonstration of safety and immunogenicity in adults, a 3 x 2 x 2 modified factorial design will compare the effectiveness of the route of immunization and the delivery system in two age groups of children. Serum and saliva will be collected at various times prior to and following immunization and analyzed by ELISA for antibody activity to MS antigens. In a second Aim, saliva and plaque samples from molar teeth will be collected to characterize the establishment of infection with MS on newly erupted molar teeth. Factors such as Dental caries, diet, salivary IgA anti-MS, level of MS in saliva and plaque of erupted teeth will be evaluated for their association with the timing of colonization of newly erupting teeth. The third Aim is to determine the effect of mucosal immunization of children on colonization with MS of virgin tooth surfaces as they erupt (i.e., permanent molar teeth). Saliva, serum and plaque samples will be collected following an immunization that will correspond with the time that permanent molar teeth are erupting, in order to determine if the time to colonization of MS is abrogated as a result of the induced immune response. The information gained regarding the mechanisms involved in the induction of mucosal immune responses in children will be of significant importance in the development of approaches to induce mucosal immunity for the prevention of infectious diseases, including Dental caries and periodontal disease.