My current NIH funded work focuses on investigations of the basic mechanisms of mucosal and systemic immunity protective against mucosally transmitted, chronic intracellular pathogens. Most of my research involves 2 model pathogens, the protozoan parasite Trypanosoma cruzi, and Mycobacterium tuberculosis (Mtb). Molecular biological and immunological techniques are being used to develop and test new vaccines in animal models and human vaccine trials. We have identified a promising T. cruzi vaccine candidate and shown that molecular vaccines expressing this antigen can provide robust mucosal and systemic protection mediated by a combination of CD4+ Th1 cell, CD8+ T cell and antibody responses. We have developed TCR transgenic mice that express T. cruzi-specific T cells, and are investigating the specific numbers of CD4+ and CD8+ T cells and the interactions between these cells required for the development of protective immunity. In addition, I have served as the PI of 10 human vaccine trials with BCG, the only TB vaccine currently available. These clinical trials were designed to investigate whether mucosal vaccinations or booster vaccinations with BCG or other new vaccines could enhance the levels of protective immunity induced by TB vaccination. These trials have provided human samples being used to identify the specific subsets of mucosal and systemic immune responses important for protective immunity, and the specific mycobacterial antigens that induce protective responses. With these samples we demonstrated for the first time that human gamma9/delta2 T cells develop protective memory responses after BCG vaccination and with RO1 funding are currently investigating the protective mechanisms mediated by these cells. Based on my research experience, I have broad expertise in both murine and human T cell studies.