EXPERIMENTAL LEPROSY & VACCINE STUDIES IN MONKEYS: MYCOBACTERIA

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We analyzed and evaluated longitudinal immunologic data gathered over a 3-4 year period post vaccination (PV) (with live BCG or BCG + heat-killed Mycobacterium leprae, HKML), post-boosting (PB) and post-challenge (PC) with live ML. Rhesus monkeys (RM) [paucibacillary (PB)-prone, as a species] were significantly protected clinically by BCG or BCG + HKML; sooty mangabey monkeys (SMM) [multibacillary (MB)-prone, as a species] were partially protected by BCG alone, but were rendered clinically more susceptible by BCG + HKML. Consistent parallels were seen between clinical results and blastogenic responses of blood mononuclear cells to ML antigens and to tuberculin, serum anti-phenolic glycolipid-I (PGL-I) antibody isotype (IgG & IgM) responses, serum PGL-I antigen levels, blood lymphocyte subsets carrying CD4, CD8, CD16, CD20, CD4CD29 and CD4CD45 phenotypic markers and lepromin skin test results. There are multiple complex, interrelated dose-dependent relationships in immunologic responses to ML antigens that determine leprosy susceptibility/resistance. The mechanisms may involve subtle differences between RM and SMM in cytokine production and/or responses, which model responses in individual humans with PB vs MB predispositions. Studies are in progress to determine comparative cytokine profiles by PCR in longitudinally-obtained lesion biopsies from animals in this study to help