Liposomal Recombinant Vaccine and Caries Immunity

脂质体重组疫苗与龋齿免疫

基本信息

批准号：
8071664
负责人：
NOEL K CHILDERS
金额：
$ 28.65万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-14 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8071664
关键词：
6 year old Adjuvant Adult Affect Age Age-Months Antibodies Antibody Formation Antigens Binding Child Childhood Chimeric Proteins Cloning Communicable Diseases Dental caries Development Diet Disease Emerging Communicable Diseases Enzyme-Linked Immunosorbent Assay Genetic Glucans Glucosyltransferase Glucosyltransferases Immune response Immune system Immunity Immunization Infant Infection Liposomes Methods Modeling Molar tooth Molecular Biology Mucosal Immune Responses Mucosal Immunity Mucous Membrane Mus Nose Nursery Schools Oral Periodontal Diseases Preparation Prevention Proteins Recombinant Vaccines Recombinants Research Route Safety Saliva Salivary Salivary immunoglobulin A Sampling Serum Streptococcus mutans System Technology Time Tonsil Tooth structure Vaccine Antigen Vaccines Virulence age effect age group compare effectiveness design immunogenic immunogenicity interest microbial colonization oral pathogen pathogen phase 1 study prevent response tool tooth surface vaccine development

项目摘要

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.

描述（由申请人提供）：粘膜免疫系统是针对病原体的重要第一道防线，该病原体通过通过粘膜组织定植或侵袭疾病，包括各种儿童疾病，例如龋齿。然而，对儿童中的粘膜免疫系统及其在粘膜免疫后具有唾液免疫反应反应的能力知之甚少。婴儿病原体突变链球菌（MS）的初始“感染窗口”出现在18-24个月大时，这是爆发原发性摩尔牙齿的时代。有人提出，当易感牙齿爆发时，例如永久摩尔牙齿时，其他“窗户”打开。因此，在出现“处女”牙齿之前，唾液抗体反应诱导了对MS的反应，可能会消除MS的牙齿定植。此应用的目的是确定在摄入型和葡萄糖基转移酶（SBR-GLU）中，由Agl/LL和葡萄糖基转移酶（SBR-GLU）响应新的反应，如果摩尔萨斯群体的启发，则含量为MOLOG的旋转量是否会涉及新的，如果摩尔群降解，则是否会涉及新的反应，该蛋白会通过新的反应来确定，如果摩尔群的启发构建了新的，如果摩尔群的启发，则含量的旋转s。多发性硬化症。在第一个目标中，在开始对儿童进行SBR-GLU进行研究之前，将对成人进行I期研究。在演示成人的安全性和免疫原性后，3 x 2 x 2修改后的阶乘设计将比较两个年龄段儿童的免疫途径和输送系统的有效性。血清和唾液将在免疫之前和之后的不同时间收集，并由ELISA分析以抗原抗原的抗体活性。在第二个目标中，将收集来自摩尔牙齿的唾液和斑块样品，以在新爆发的摩尔牙齿上以MS建立感染。龋齿，饮食，唾液IgA抗MS，唾液中MS水平以及喷发牙齿的牙齿等因素将与新爆发牙齿定植的时间有关。第三个目的是确定儿童在爆发时用牙齿牙齿表面MS定殖（即永久摩尔牙齿）的粘膜免疫的影响。免疫后将收集唾液，血清和斑块样品，该免疫将与永久摩尔牙齿爆发的时间相对应，以确定由于诱导的免疫反应而消除了MS定植的时间。关于儿童诱导粘膜免疫反应涉及的机制所获得的信息将在开发诱导粘膜免疫的方法中至关重要，以预防传染病，包括龋齿和牙周疾病。