Liposomal Recombinant Vaccine and Caries Immunity

描述（由申请人提供）：粘膜免疫系统是抵御病原体的重要第一道防线，这些病原体通过粘膜组织定植或侵入导致疾病，包括各种儿童疾病，如龋齿。然而，关于儿童粘膜免疫系统及其在粘膜免疫后唾液免疫反应的能力知之甚少。婴儿口腔致病菌变形链球菌（MS）最初的“感染性窗口期”发生在18-24个月大，此时乳牙正在长出。有人提出，当易感牙齿（如恒磨牙）长出时，其他“窗口”也会打开。因此,该应用的目的是确定青春期前（10-12岁）和学龄前（5-6岁）儿童在粘膜免疫后对突变链球菌免疫原性亚基Agl/ll和葡萄糖基转移酶（SBR-GLU）组成的重组嵌合蛋白作出反应的能力，并确定诱导的反应是否会发生在第一个目标中，在开始SBR-GLU在儿童中的研究之前，将进行成人的I期研究。在证明成人的安全性和免疫原性之后，一个3 × 2 × 2的修正因子设计将比较免疫途径和给药系统在两个年龄组儿童中的有效性。将在免疫前后的不同时间收集血清和唾液，并通过ELISA分析对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MS感染在新出的臼齿上的建立。龋齿、饮食、唾液IgA抗多发性硬化症、唾液中多发性硬化症水平和牙菌斑等因素将被评估，以确定它们与新出牙定植时间的关系。第三个目的是确定儿童粘膜免疫对萌牙（即恒磨牙）初牙表面MS定植的影响。唾液、血清和牙菌斑样本将在免疫接种后收集，与恒磨牙出牙的时间相对应，以确定MS的定植时间是否因诱导免疫反应而被废除。所获得的关于诱导儿童粘膜免疫反应的机制的信息将对开发诱导粘膜免疫的方法以预防包括龋齿和牙周病在内的传染病具有重要意义。

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.