Liposomal Recombinant Vaccine and Caries Immunity

描述(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，这些病原体通过黏膜组织的定植或入侵而致病，包括各种儿童疾病，如龋齿。然而，对儿童的黏膜免疫系统及其在黏膜免疫后对唾液免疫反应的能力知之甚少。婴儿口腔病原体变形链球菌(MS)最初的“感染窗口”出现在18-24个月大的时候，也就是乳磨牙萌出的时候。已经有人提出，当易感牙齿萌出时，例如恒磨牙，其他“窗”会打开。本应用的目的是确定青春期前(10-12岁)和学龄前(5-6岁)儿童对变形链球菌免疫原性亚基和葡萄糖基转移酶(SBR-GLU)的重组嵌合蛋白的反应能力，并确定诱导的反应是否会消除MS对新长出的磨牙的定植。将对成年人进行第一阶段的研究。在成人中证明了安全性和免疫原性之后，3x2x2改进的析因设计将比较免疫途径和递送系统在两个年龄组儿童中的有效性。在免疫前后不同时间采集血清和唾液，用酶联免疫吸附试验检测血清和唾液中MS抗原的抗体活性。在第二个目标中，将收集磨牙的唾液和菌斑样本，以确定新长出的磨牙是否感染了多发性硬化症。如龋齿、饮食、唾液中的IgA抗MS抗体、唾液中的MS水平和萌出牙的菌斑等因素将被评估，以确定它们与新萌出牙的定植时间的关系。第三个目的是确定儿童黏膜免疫对萌出时原始牙齿表面(即恒磨牙)多发性硬化症定植的影响。唾液、血清和菌斑样本将在与恒磨牙萌出时间相对应的免疫后收集，以确定MS的定植时间是否由于诱导的免疫反应而被取消。所获得的有关儿童黏膜免疫反应诱导机制的信息将对开发诱导黏膜免疫以预防包括龋齿和牙周病在内的传染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.