ANTI TUBERCULOSIS CANDIDATE VACCINE TESTING IN RHESUS MONKEYS

8例正常RM经光纤接种MTB 支气管镜检查。4人接种了毒力较低的H37Rv毒株，4人接种了H37Rv毒株 通过光纤获得了高毒力的Erdman菌株 支气管镜检查。接种高剂量H37Rv(6)的两只猴子 X 106 CFU)开发了广泛的多焦点扩展和合并 肉芽肿中央有广泛的坏死区，中性粒细胞 接菌后右叶的渗透和矿化 在激发后5周和11周(Wk)。猴子们正在接受低潮 剂量为H37Rv(30CFU)的支气管内有肉芽肿病变 感染后18wk出现淋巴结转移。损伤表明低剂量的 结核分枝杆菌H37Rv至少在短期内由 猴肺中的自然防御和更高的 细菌的剂量在没有细菌的情况下会产生显著的组织反应 败血症扩散的证据。两个高剂量(150 CFU)Erdman 受体猴子患上广泛的肉芽肿性肺炎， 胸膜炎，支气管结节坏死伴微小肉芽肿 肝、肾等部位7-9周。…的出现 肺炎和病程与产生的疾病大致相当。 高剂量(&gt；106)H37Rv。2只小剂量Erdman免疫猕猴 (15 CFU)在挑战后9周和19岁时保持临床正常 WK临床表现轻微，但纤维性肉芽肿 肺部病变扩散至其他组织。我们的结论是 通过小剂量接种Erdman可以建立慢性病 与H37Rv相比，产生的病变分布更广 紧张。资助基础补助金，风险研究出版物Didier PJ， Blanchard JL和Gormus BJ.正常恒河猴的肺结核 结核分枝杆菌H37Rv产生的猴子。Am J Soc trop Med HYG 57：156,1997[摘要]。Didier PJ，Blanchard JL和Gormus BJ。 小剂量结核分枝杆菌引起的慢性肺结核 (Erdman)在恒河猴中。中国社会医学杂志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.