Opportunities for Dental Research in Salivary Gland Immunobiology at Stony Brook

石溪分校唾液腺免疫生物学牙科研究机会

• 批准号: 9812028
• 负责人: STEVEN D LONDON
• 金额: $ 46.96万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-10 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9812028
• 关键词: AQP1 gene; Academic Research Enhancement Awards; Acquired Immunodeficiency Syndrome; Address; Animal Model; Antigens; Applications Grants; Award; B-Lymphocytes; Bacteria; Biologic Characteristic; Biological Models; Cannulations; Clinical; Clinical Trials; Critical Thinking; DNA; Data; Defense Mechanisms; Dental Research; Dental Schools; Dental Students; Development; Distal; Duct (organ) structure; Environment; Erythropoietin; Exposure to; Feces; Fostering; Funding; Goals; Grant; HIV; Homeostasis; Human; Immune response; Immunity; Immunization; Immunobiology; Immunoglobulin A; Immunoglobulin G; Infection; Infection prevention; Injections; Institution; Interferons; Knowledge; Lead; Major salivary gland structure; Medicine; Membrane; Methods; Mission; Modeling; Mucosal Immune Responses; Mucosal Immune System; Mucosal Immunity; Mucous Membrane; Murid herpesvirus 1; Norovirus; Oral; Oral cavity; Oral mucous membrane structure; Outcome; Outcome Study; Parotid Gland; Pathology; Perfusion; Physiological; Positioning Attribute; Procedures; Process; Proteins; Public Health; Recording of previous events; Research; Role; Route; Saliva; Salivary Glands; Scholarship; Serum; Site; Stensen' s duct; Student recruitment; Students; Submandibular gland; Subunit Vaccines; Surface; Surgical incisions; T-Lymphocyte; Therapeutic; Tissues; United States National Institutes of Health; Upper digestive tract structure; Vaccination; Vaccines; Vagina; Viral; Virus; Virus Diseases; Vision; adenoviral-mediated; alpha 1-Antitrypsin; base; burden of illness; career; clinical care; cost efficient; disability; foot; innovation; interest; keratinocyte growth factor; mucosal site; mucosal vaccine; novel; pathogen; programs; protein expression; response; skills; therapeutic gene; vaccination strategy; vaccine candidate; vaccine development; vaccine evaluation; vector

Project Summary/Abstract: Effective immunization strategies are necessary to reduce the burden of disease from pathogens that initiate their infectious processes at mucosal surfaces and thus, understanding the mechanisms of defense in these tissues is an important endeavor in vaccine development. Most vaccines are given parentally via injection and they do not necessarily generate an adequate immune response at mucous membranes. Therefore, it is important that the evaluation of vaccine candidates address the induction of both mucosal and systemic immunity that would be reflected in prevention of infection or reduction in pathogen replication at the initial site of pathogen entry. The salivary glands are important mucosal tissues in the oral cavity and upper gastrointestinal tract. Due to several physical and biological characteristics, the salivary glands can potentially be a unique target site for the induction of both mucosal and systemic immunity. We described a model of a focused salivary gland inoculation with murine cytomegalovirus, which provided direct evidence that the salivary gland acts as a mucosal inductive site in addition to an effector site in oral mucosal immunity, and in addition, antigenic stimulation of the salivary gland was sufficient to induce immunity at proximal and distal mucosal sites as well as systemic sites. The central hypothesis, which was formulated based on our preliminary data, is that immunization of the salivary glands with DNA subunit vaccines will elicited effective and functionally protective immunity at both mucosal and systemic sites and thus, provide an alternative, potentially more effective, and cost-efficient approach for vaccination against pathogens that infect through mucosal surfaces. The objective of this application is to evaluate the induction of mucosal and systemic immunity after salivary gland inoculation with two distinct viral infection models; (i) norovirus as a model gut infection, and (ii) HIV as a model to study AIDS vaccination strategies. This research is innovative and has the potential to provide a new and unique method of vaccination that may be especially applicable against infections that start and/or progress in the mucosal membranes. This project is ideally suited for a short-term summer exposure to research of interest to the “dental student” that can easily be expanded over the course of the academic year. The proposed project is significant since the outcomes of these studies will add greatly to our understanding of salivary gland induced mucosal immunity. Thus, the long-range vision for how this research will impact clinical care is that effective, DNA or other vaccine strategies, delivered through the salivary glands, will be developed and provide a new and unique method of vaccination that may be especially applicable against infections that start and/or progress in the mucosal membranes. The award of this AREA grant will meet the goals of student research at the School of Dental Medicine by fostering scholarship and critical thinking skills, by adding to the body of scientific knowledge, and by facilitating recruitment of students into academic, dental research careers.

项目概要/摘要： 有效的免疫策略对于减少病原体的疾病负担是必要的， 在粘膜表面启动感染过程，从而了解防御机制 是疫苗研发中的一项重要奋进。大多数疫苗都是通过以下途径给予的： 注射，并且它们不一定在粘膜处产生足够的免疫应答。 因此，重要的是评价候选疫苗，解决粘膜免疫和免疫应答的诱导。 和全身免疫，这将反映在预防感染或减少病原体复制 在病原体进入的初始位置。唾液腺是口腔中重要的粘膜组织， 上消化道由于几个物理和生物学特性，唾液腺可以 可能是诱导粘膜和全身免疫的独特靶位点。我们描述了一个 小鼠巨细胞病毒的集中唾液腺接种模型，这提供了直接证据 唾液腺在口腔粘膜中除了作为效应位点外，还作为粘膜诱导位点， 免疫力，此外，唾液腺的抗原刺激足以诱导免疫力， 近端和远端粘膜部位以及全身部位。核心假设是， 根据我们的初步数据，用DNA亚单位疫苗免疫唾液腺， 在粘膜和全身部位均引发有效的和功能性保护性免疫， 一种替代的、可能更有效的、成本效益高的针对病原体的疫苗接种方法， 通过粘膜表面感染。本申请的目的是评估粘膜诱导 唾液腺接种两种不同的病毒感染模型后的全身免疫;（i）诺如病毒 作为肠道感染的模型，以及（ii）HIV作为研究艾滋病疫苗接种策略的模型。本研究是 具有创新性，并有可能提供一种新的和独特的疫苗接种方法， 适用于在粘膜中开始和/或发展的感染。该项目是理想的 适合短期夏季接触感兴趣的研究“牙科学生”，可以很容易地 在整个学年中不断扩大。拟议项目意义重大，因为 这些研究将大大增加我们对唾液腺诱导的粘膜免疫的理解。因此 关于这项研究将如何影响临床护理的长期愿景是，DNA或其他疫苗 将开发通过唾液腺递送的策略，并提供一种新的独特方法 特别适用于在粘膜中开始和/或发展的感染的疫苗接种 膜。该地区补助金的授予将满足学生在牙科学院的研究目标 医学通过培养学术和批判性思维能力，通过增加科学知识的主体， 以及促进学生进入学术，牙科研究职业的招聘。