ANTI TUBERCULOSIS CANDIDATE VACCINE TESTING IN RHESUS MONKEYS

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Eight normal RM were inoculated with MTB via fiberoptic bronchoscope. Four received the less virulent H37Rv strain and four received the highly virulent Erdman strain via fiberoptic bronchoscope. Both monkeys that received the high dosage of H37Rv (6 X 106 cfu) developed extensive multifocal expansile and coalescing granulomas with broad central zones of necrosis, neutrophilic infiltration, and mineralization in the inoculated right lobe of the lung by 5 and 11 weeks (wk) post-challenge. Monkeys receiving the low dose of H37Rv (30 cfu) had granulomatous lesions in the bronchial lymph nodes 18 wk after infection. Lesions suggest that low doses of M. tuberculosis H37Rv are controlled, at least in the short term, by natural defenses in the simian lung and that challenge with higher doses of bacteria produces significant tissue response without evidence of septicemic spread. Two high dose (150 cfu) Erdman recipient monkeys developed extensive granulomatous pneumonia, pleuritis, and bronchial node necrosis with microgranulomas in the liver, kidney, and other sites in 7-9 weeks. The appearance of pneumonia and time course were roughly comparable to disease produced by high dose (>106) H37Rv. The 2 low dose Erdman-inoculated monkeys (15 cfu) remained clinically normal 9 weeks post-challenge and at 19 wk had minimal clinical manifestations, but fibrotic granulomatous pulmonary lesions with spread to other tissues. We conclude that chronic disease can be established by low dose Erdman inoculation with a wider distribution of lesions being produced compared to the H37Rv strain. FUNDING Base Grant, Venture Research PUBLICATIONS Didier PJ, Blanchard JL and Gormus BJ. Pulmonary Tuberculosis in Normal Rhesus Monkeys Produced by M. tuberculosis H37Rv. Am J Soc Trop Med Hyg 57:156, 1997 [Abstract]. Didier PJ, Blanchard JL and Gormus BJ. Chronic Tuberculosis Produced by Low Dosage of M. tuberculosis (Erdman) in Rhesus Monkeys. Am J Soc Trop Med Hyg 59:361, 1998.