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，病原体通过粘膜组织定植或入侵而引起疾病，包括多种儿童疾病，例如龋齿。然而，人们对儿童粘膜免疫系统及其在粘膜免疫后响应唾液免疫反应的能力知之甚少。婴儿中口腔病原体变形链球菌 (MS) 的初始“感染窗口”发生在 18-24 个月大，此时乳磨牙正在萌出。有人提出，当易受影响的牙齿（例如恒磨牙）萌出时，其他“窗口”会打开。因此，在“原始”牙齿出现之前诱导唾液抗体对 MS 的反应可能会消除 MS 在这些牙齿上的定植。本申请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由来自变形链球菌的Agl/II和葡萄糖基转移酶（SBR-GLU）的免疫原性亚基组成的重组嵌合蛋白作出反应的能力，并确定所诱导的反应是否会消除MS对新萌出的磨牙的定植。第一个目标是，在开始儿童 SBR-GLU 研究之前，将对成人进行 I 期研究。在成人中证明安全性和免疫原性后，3 x 2 x 2 改良因子设计将比较两个年龄组儿童中免疫途径和递送系统的有效性。将在免疫之前和之后的不同时间收集血清和唾液，并通过 ELISA 分析针对 MS 抗原的抗体活性。第二个目标是收集臼齿的唾液和菌斑样本，以表征新萌出的臼齿上 MS 感染的情况。将评估诸如龋齿、饮食、唾液 IgA 抗 MS、唾液中 MS 水平和萌出牙齿菌斑等因素与新萌出牙齿定植时间的关系。第三个目标是确定儿童粘膜免疫对萌出时原始牙齿（即恒磨牙）表面 MS 定植的影响。将在与恒磨牙萌出时间相对应的免疫接种后收集唾液、血清和牙菌斑样本，以确定 MS 定植时间是否因诱导的免疫反应而消除。所获得的有关诱导儿童粘膜免疫反应的机制的信息对于开发诱导粘膜免疫以预防传染病（包括龋齿和牙周病）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.