Research Project
8143122
DESCRIPTION (provided by applicant): Despite close to 40 million HIV-infected individuals worldwide and millions of new infections each year, intense research in the field of HIV vaccine development has not yet lead to a licensed prophylactic or therapeutic vaccine. Regardless of the route of infection, HIV targets mucosal cells of the gastrointestinal, respiratory and genitourinary tracts, at both early and late stages of infection. HIV transmission through the female genital tract (FGT) remains a major route of infection. Thus, generation of immune responses at this mucosal portal of HIV entry, as well as systemic sites would be advantageous. Induction of immune responses at mucosal sites requires safe and effective immune enhancing delivery systems and adjuvants, which currently do not exist in licensed form mainly due to their toxicity issues. In phase I of this proposal, we will test in mice the effectiveness of a novel and safe formulation designated mucosal immune enhancing delivery system (MIDS) for mucosal (intra-nasal) and systemic (intra-dermal) administration of an HIV-envelope protein with the goal of inducing immunity in both FGT and systemic tissues. The specific aims will include first optimization of the MIDS formulations and induction of in vitro innate responses in epithelial and antigen-presenting cells (APC), followed by in vivo induction in mice of mucosal and systemic innate and adaptive responses by antigen-presenting, B and T cells, including regulatory (Treg), helper (TH) and cytotoxic (CTL). In phase II, we will test the immunogenicity and protective efficacy of immunizations with MIDS with HIVenv proteins in female rhesus macaques followed by intra-vaginal challenge with SHIV. PUBLIC HEALTH RELEVANCE: Currently, there are no licensed vaccines against infections with HIV. This project pertains to designing a novel, safe and effective Mucosal Immune-enhancing Delivery System for HIV vaccine development that can protect the public against new infections with the HIV virus.
