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.
Project Narative: The proposed research is relevant to public health because effective immunization strategies are necessary to reduce the burden of disease from pathogens that initiate their infectious processes at mucosal surfaces. We have developed a new model of focused salivary gland immunization that has allowed us to determine that the salivary gland functions as an inductive site in the context of the common mucosal immune system. Thus, the proposed research is relevant to the part of NIH?s mission that pertains to reducing illness and disability, and in reference to this RFA stimulates research in educational institutions that fosters scholarship and critical thinking skills, adds to the body of scientific knowledge, and facilitates recruitment of students into academic research careers.
