EXPERIMENTAL LEPROSY VACCINE STUDIES

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The goals are to: 1) continue longitudinal observations on normal monkeys and those immunized with BCG or BCG + heat-killed mycobacterium leprae (HKML) followed by challenge with live ML; 2) determine: the effects of immunization on in vitro blastogenesis to whole ML and to ML antigens (Ag); serum ELISA's for anti (A)-PGL-I and A-LAM IgG and IgM antibodies; skin test reactivity with lepromin; and mononuclear cell subset identifications in leprosy lesions by monoclonal Ab staining for phenotypic markers and cytokine profiles by a PCR method to identify cytokine m-RNA's; 3) determine if immunization protects against the appearance of clinical leprosy; 4) determine the relative value of rhesus (RM) vs sooty mangabey monkeys (SMM) as models for testing anti-leprosy vaccines; and 5) evaluate longitudinally the clinical, pathologic and immunologic effects of live ML challenge in unvaccinated and BCG- or BCG/HKML vaccinated RM and SMM. Although the number of leprosy cases worldwide has decreased in recent years, our observations in monkeys suggest that there is a potential for AIDS to reverse that trend by increasing the susceptibility of AIDS- infected leprosy contacts to leprosy and by shifting existing cases towards the LL end of the spectrum, increasing the presence of M. leprae in the environment. Thus AIDS may increase risk of contagion and loss of control of leprosy. The best leprosy preventative would be an anti-leprosy vaccine that would protectively immunize those at risk in endemic areas. Thus, we will evaluate whether or not BCG or BCG+ HKML can provide such protection against M. leprae. We also propose to investigate the nature of early and sequentually appearing predisposing immunologic factors that may be related to susceptibility or resistance to leprosy, by observing longitudinally, immunologic phenomena within leprosy lesions utilizing new technology such as cytokine m-RNA identifications in lesion biopsies using a PCR method, as well as techniques previously shown to be related to propensity to the development for the polar forms of leprosy: blastogenesis, antibody responses to ML Ag's and lepromin skin testing. Studies in humans have shown the end result of long-standing leprosy, but it is not ethically feasible to study longitudinally untreated leprosy beginning prior to ML infection, to learn the initial susceptibility/resistance factors. The proposed studies will attempt to address that issue by searching for changes in immunologic parameters that parallel susceptibility/resistance.