|
Research Interests:
|
My research interests comprise mechanisms of immunity against Rickettsia and Ehrlichia, identification of antigens and their presentation to stimulate protective immunity against spotted fever group and typhus group rickettsiae, Ehrlichia chaffensis, and E. canis, emerging and re-emerging ehrlichioses and rickettsioses including
novel tropical infections, R. felis infection, epidemic louse-borne typhus, and human monocytotropic ehrlichiosis, complete sequencing of the genome of R. typhi, and microarray analysis of host defense and pathogenesis genes that are activated or inactivated in mouse models of susceptibility and resistance to rickettsial infection. The latter project and longterm goals of developing effective vaccines against R. rickettsii and R. prowazekii have biodefense as well as public health and tropil medicinal applications. Our NIH R01 projects employ mouse and in vitro models of human monocytotropic ehrlichiosis and spotted fever group rickettsioses to evaluate the roles of antibody an cellular immunity including cytotoxic T-lymphocyte activity, and cytokines in protective immunity. Protective T- and B-cell epitopes of the 28 kDa multigene family of proteins are under investigation as a p28 locus vaccine. For spotted fever group rickettsiae, we are focusing not only on identifying broadly crossprotective T- and B-cell epitopes but also CD8 T-lymphocyte targeting chemokines and the mechanisms by which they and CD8 CTL serve as immune effectors. Pilot studies are underway to establish methods for inactivation of rickettsial genes, selection of attenuated mutants, identification of the inactivated genes, and evaluation for attenuation and protective efficacy in animal models towards the goal of developing stably, multiply attenuated vaccines against typhus and spotted fever rickettsioses. A Clayton Foundation-funded project currently focuses on use of the genes of E. canis that we have discovered to the develop a vaccine against canine monocytotropic ehrlichiosis as veterinary preventive medicine goal as well as a stepping stone toward the developing of a
vaccine against human monocytotropic ehrlichiosis, a
highly prevalent diagnostically difficult, life-threatening emerging infectious disease.
|
