Opportunities for Dental Research in Salivary Gland Immunobiology at Stony Brook

项目摘要/摘要： 有效的免疫策略是必要的，以减少来自病原体的疾病负担 在粘膜表面启动它们的感染过程，从而了解防御机制 在这些组织中是疫苗开发的一项重要努力。大多数疫苗是通过父母通过 注射，它们不一定会在粘膜上产生足够的免疫反应。 因此，重要的是，对候选疫苗的评估应解决对两种粘膜的诱导 以及系统免疫，这将反映在预防感染或减少病原体复制上 在病原体进入的初始位置。唾液腺是口腔中重要的粘膜组织， 上胃肠道。由于几个物理和生物学特性，唾液腺可以 有可能成为诱导粘膜免疫和系统免疫的独特靶点。我们描述了一个 小鼠巨细胞病毒涎腺接种模型的建立 唾液腺在口腔粘膜中除了作为效应部位外，还起着粘膜诱导部位的作用 免疫，此外，唾液腺的抗原刺激足以在 近端和远端粘膜部位以及全身部位。中心假说，这是公式化的 根据我们的初步数据，用DNA亚单位疫苗免疫唾液腺将 在粘膜和全身两个部位激发有效的功能保护性免疫，从而提供 针对病原体的另一种可能更有效、更具成本效益的疫苗接种方法 通过粘膜表面感染。这项应用的目的是评估粘膜的诱导 唾液腺接种两种不同的病毒感染模型后的系统免疫；(I)诺沃克病毒 作为肠道感染的模型，和(Ii)以艾滋病毒为模型来研究艾滋病疫苗接种策略。这项研究是 具有创新性，并有可能提供一种新的独特的疫苗接种方法，这种方法可能特别 适用于开始和/或进展在粘膜中的感染。这个项目是最理想的 适合在暑期短期接触“牙科学生”感兴趣的研究，这些研究很容易 在整个学年的过程中不断扩大。拟议的项目意义重大，因为 这些研究将极大地加深我们对唾液腺诱导的粘膜免疫的了解。因此， 这项研究将如何影响临床护理的长远愿景是有效的，DNA或其他疫苗 通过唾液腺传递的策略将被开发并提供一种新的和独特的方法 可特别适用于开始和/或进展在粘膜中的感染的疫苗接种 膜。授予这一领域的资助将满足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， 并通过促进学生进入学术和牙科研究职业。

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.