Leukocyte trafficking in the lung; leukocyte/epithelium interactions. My lab focuses on understanding how HIV infection is transmitted by heterosexual contact and developing vaccines and microbicides to prevent HIV transmission to women. Much of this work uses the simian immunodeficiency virus (SIV) model of heterosexual HIV transmission and pathogenesis. We study 4 areas critical to developing interventions to heterosexual HIV transmission: 1) viral factors (dose, phenotype, etc..,) in vaginal transmission, 2) natural history (virus dissemination patterns and host immune response patterns) of SIV infection after vaginal transmission, 3) nature of effective systemic and mucosal antiviral immune responses , 4) understanding the range of antiviral immunity that can be elicited in the female genital tract and eliciting the strongest responses through vaccination. A major goal of the monkey vaccine and microbicide studies is to parallel these studies with planned human clinical trials in an effort to determine the extent to which the monkey model predicts the results of the clinical trial. We have a an PO1 funded that includes non-human primate studies and human clinical trials that were designed in parallel and that will use the same vaccine lots with the goal of comparing mucosal and systemic immune responses of rhesus macaques and humans to the same vaccination protocol. Our current golas are to: (1) define the dissemination pathway of SIV from the genital tract to systemic lymphoid tissues, and the corresponding pattern of innate and adaptive immune responses after intravaginal SIV inoculation, (2) define the role of viral recombination in maintaining the viral population genetic diversity that is a prerequisite for mucosal SIV transmission and virulence, (3) determine how small molecules (TLR-ligands) elicit innate antiviral immune responses after application to mucosal surfaces and determine if these innate responses can protect monkeys from subsequent mucosal (respiratory or genital tracts) challenge with SIV are acute respiratory pathogens (measles virus, influenza virus), and (4) determine the relative ability of several HIV vaccine candidates to elicit mucosal and systemic immune responses and control viral replication in rhesus monkeys. All our work involves extensive collaborations with investigators at pharmaceutical companies and academic institutions throughout the United States , Canada and Europe.
Visit Dr. Miller's website: http://faculty.vetmed.ucdavis.edu/faculty/cjmiller/