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.

项目摘要/摘要： 有效的免疫策略对于减轻病原体造成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 在这些组织中进行疫苗开发是一项重要的努力。大多数疫苗是通过父母给予的 注射后，它们不一定会在粘膜处产生足够的免疫反应。 因此，对候选疫苗的评估必须解决粘膜和粘膜的诱导问题，这一点很重要。 以及全身免疫，这将反映在预防感染或减少病原体复制上 在病原体进入的最初部位。唾液腺是口腔中重要的粘膜组织， 上消化道。由于多种物理和生物学特性，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 鼠巨细胞病毒唾液腺集中接种模型，提供了直接证据 唾液腺除了口腔粘膜的效应位点外，还充当粘膜感应位点 免疫，此外，唾液腺的抗原刺激足以诱导免疫 近端和远端粘膜部位以及全身部位。提出的中心假设 根据我们的初步数据，用 DNA 亚单位疫苗对唾液腺进行免疫将 在粘膜和全身部位引发有效的功能性保护性免疫，从而提供 另一种可能更有效且更具成本效益的病原体疫苗接种方法 通过粘膜表面感染。本应用的目的是评估粘膜的诱导 唾液腺接种两种不同病毒感染模型后的全身免疫； (一) 诺如病毒 作为肠道感染模型，以及 (ii) HIV 作为研究艾滋病疫苗接种策略的模型。这项研究是 创新并有潜力提供一种新的、独特的疫苗接种方法，该方法可能特别有效 适用于抵抗在粘膜中开始和/或进展的感染。这个项目非常理想 适合短期暑期接触“牙科学生”感兴趣的研究，这些研究很容易 在整个学年中不断扩大。拟议项目意义重大，因为 这些研究将极大地增进我们对唾液腺诱导的粘膜免疫的理解。因此， 这项研究将如何影响临床护理的长期愿景是 DNA 疫苗或其他疫苗是否有效 将开发通过唾液腺传递的策略并提供一种新的独特方法 疫苗接种可能特别适用于预防在粘膜中开始和/或进展的感染 膜。该 AREA 补助金的授予将实现牙科学院学生研究的目标 医学通过培养学术和批判性思维能力，通过增加科学知识体系， 并促进招收学生进入学术、牙科研究职业。