Mucosal tissues are the major portal of entry and initial sites of infection for many pathogens, including human immunodeficiency virus (HIV). However, there is no methodology currently available that can elicit protective immunity in mucosal tissues in a safe and effective manner. The investigator?s long-term goal is to develop novel biomaterial-based approaches for vaccination against infectious pathogens. In this CAREER application, the investigator proposes to address this global challenge by investigating the impact of material properties of vaccine delivery systems on immune activation in mucosal lymphoid tissues. The new knowledge gained through this interdisciplinary effort will advance the understanding of immune responses to biomaterials and address current technical challenges facing vaccine development.
The overall goal of the project is to test the hypothesis that ?pathogen-mimicking? nanomaterials engineered for optimized delivery of vaccine components to mucosal lymphoid tissues will induce robust, concerted T and B cell immune responses in mucosal tissues. To achieve this, the investigator will develop a series of multilamellar vaccine platforms (MVPs), employ HIV candidate antigens, and define structure-function relationships that govern the interaction between biomaterials and the immune system in cellular, tissue, and organism levels in murine models of mucosal vaccination. The proposed studies will (1) generate new information on how material properties of vaccine delivery systems dictate antigen delivery and presentation, (2) shed new light on new nanomaterial-based approaches to modulate mucosal immunity, (3) dissect the role of nanocarriers on innate and adaptive immunity, and (4) delineate pathways to safely elicit protective immunity against HIV. Furthermore, the MVP technology established in this project could be easily adopted to other infectious pathogens, thus broadening the scope of the work beyond HIV vaccine design and impacting a wide range of disciplines, including biomaterials, drug delivery, and immunology. The investigator also seeks to integrate research with educational activities designed to raise excitement and interest in the emerging field of nanoscience. This will be achieved by (a) engaging underrepresented minorities and women to pursue careers in science and engineering; (b) training undergraduate and graduate students in the investigator?s laboratory; and (c) communicating research to the general public. The broader public, particularly underrepresented high school students in a low-income area of Detroit, will be reached by developing a series of new Saturday morning workshops, entitled ?MVPs in Michigan, which will feature science demonstrations on nanotechnology, nanomedicine, and vaccine design.