ANTI TUBERCULOSIS CANDIDATE VACCINE TESTING IN RHESUS MONKEYS

8例正常RM经光纤接种结核分枝杆菌 支气管镜 四个接受毒性较低的H37 Rv菌株，四个接受毒性较低的H37 Rv菌株。 通过光纤接收了高毒性的埃德曼病毒株 支气管镜 接受高剂量H37 Rv的两只猴子（6 X106 cfu）发展为广泛的多灶性扩张和融合 嗜酸性肉芽肿，伴有广泛的中央坏死区 在接种的右叶中的渗透和矿化 攻毒后5周和11周（wk）时的肺。 猴子接受低 H37 Rv剂量（30 cfu）在支气管中有肉芽肿性病变 感染后18 wk淋巴结肿大。 病变表明低剂量的 M.至少在短期内， 猿类肺部的天然防御系统， 大量的细菌产生显著的组织反应， 败血症传播的证据 两个高剂量（150 cfu）Erdman 受体猴发展为广泛的肉芽肿性肺炎， 胸膜炎和支气管结节坏死伴微肉芽肿 肝脏、肾脏和其他部位7-9周。 的外观 肺炎和时间进程大致相当于疾病产生 高剂量（>106）H37 Rv。 2只低剂量Erdman接种猴 (15 cfu）在攻击后9周和19周时保持临床正常 wk有轻微的临床表现，但纤维化肉芽肿 肺部病变扩散到其他组织。 我们的结论是 慢性疾病可以通过低剂量Erdman接种建立， 与H37 Rv相比， 株 基金基础赠款，风险研究出版物迪迪埃PJ， Blanchard JL和Gormus BJ. 正常恒河猴肺结核 由M制作的猴子结核病H37 Rv. Am J Soc Trop Med Hyg 57：156，1997 [摘要]。 Didier PJ，Blanchard JL和Gormus BJ。 小剂量M.结核 （Erdman）在Rhesus Monkeys。 Am J Soc Trop Med Hyg 59：361，1998.

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.