EXPERIMENTAL LEPROSY/VACCINE STUDIES IN MANGABEYS

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The goals of this proposal are: 1) to evaluate protective immunity in sooty mangabey monkeys (Cercocebus atys) by challenge with viable Mycobacterium leprae after immunization with live BCG alone or in combination with two doses of heat killed, whole M. leprae. 2) to evaluate the clinical, pathologic and immunologic effects of M. leprae infection in mangabeys after vaccination and throughout the course of disease and treatment and 3) to study the nature of the immune defects in mangabey with LL leprosy. There are 12 to 15 million leprosy patients worldwide, many of them in underdeveloped areas where chemotherapy is impractical and/or too expensive. The development of an effective vaccine would obviate the necessity for therapy. Monkeys are phylogenetically similar to man, and lepromatous (L) leprosy in the mangabey monkey is clinically and immunologically similar to humans. Immunity will be assessed longitudinally before and after vaccination of mangabey monkeys by: skin testing with soluble Rees M. leprae to determine the effectiveness of vaccination. We will study immune parameters longitudinally in control, vaccinated and experimentally infected mangabeys to monitor the dynamics of leprosy-induced changes relative to the observed cyclic rhythm. We will compare control mangabeys to those with early and late LL leprosy (both disseminated and nondisseminated) to dissect the mechanism of the immune unresponsiveness induced in managabey by LL leprosy. In these studies we will monitor the following in blood mononuclear cells (MNC). 1) in vitro responses to mitogens (Con A, PHA and PWM) and to Dharmendra lepromin (D-lep); 2) binding by monoclonal antibodies; and 3) pokeweed mitogen-induced immunoglobulin plaque-forming cell numbers. Levels of serum antibodies (IgG, IgM, IgA) to M. leprae-specific phenolic glycolipid 1 antigen will be determined. Lymphocytes (L) and monocytes (MO) will be separated into subpopulations and will studied separately and in various recombinations for normal responses to D-lep. Levels of lymphokine production [gamma-interferon (gamma-IFN); interleukin 1 (IL-1) and IL-2] by the various MNC subpopulations will be determine. Pure lymphokines will be added back to cell fractions from mangabeys with LL in attempts to reconstitute normal responses to mitogens and to D-lep.