Rocky Mountain spotted fever, the most severe and widespread rickettsiosis in the United States, and boutonneuse fever, a spotted fever group rickettsiosis with an extremely widespread geographic distribution, high prevalence of undiagnosed infections, and substantial mortality in Africa, Asia, and Europe, are neglected diseases of public health importance. The timely clinical and laboratory diagnosis of these diseases is remarkably underestimated in difficulty, and no effective prevention is available. Toward the longterm goal of elucidation of the molecular structure and function of spotted fever group rickettsiae, this proposed research is focused on the identification of protective vaccinogens of Rickettsia rickettsii, R. conorii and R. montana. Recombinant DNA production of antigens of R. conorii, R. rickettsii, and R. montana will be engineered to provide sufficient quantities of antigens for use as vaccinogens and specific probes of cellular and humoral immune responses. Antigens will be characterized by reactivity with a library of anti-spotted fever group rickettsial epitopes, which has already been partially developed, including monoclonals that protects experimental animals from virulent challenge. Because the three previous historic vaccines have failed to provide protective immunity in contrast to the solid immunity conferred by prior active infection, the immunologic basis for successful and unsuccessful vaccination will be evaluated in experimental animals. Animals vaccinated with crossprotective viable rickettsiae and purified antigens will be challenged and evaluated for the kinetics of the cellular immune response (gamma- interferon and lymphocyte proliferation) and antibody response. Moreover, the elucidation of the physiologic or pathogenic functions of rickettsial molecular components will be approached by manipulation of an assay for rickettsial attachment to the host cell. The ultimate result of these experiments should be the collection of data needed for the rational design of vaccines to prevent spotted fever group rickettsiosis, a better understanding of immunity to spotted fever group rickettsiae, and determination of the rickettsial attachment mechanism.
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