ANTI TUBERCULOSIS CANDIDATE VACCINE TESTING IN RHESUS MONKEYS

在恒河猴中进行抗结核候选疫苗测试

• 批准号: 6116172
• 负责人: BOBBY J GORMUS
• 金额: $ 18.74万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116172
• 关键词: Mammalia; animal tissue; bacteria; communicable diseases; immunology; inflammation; model design /development; respiratory system; technology /technique; vaccines

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.

MTB通过光纤接种了八个正常RM 支气管镜。 四个获得了毒气较少的H37RV菌株和四个 通过光纤接收了高毒的埃德曼菌株 支气管镜。 这两只猴子都接受了H37RV的高剂量（6 X 106 CFU）开发了广泛的多灶性扩张和合并 肉芽瘤，宽阔的坏死中心区域，中性粒细胞 浸润和接种的右叶矿化 肺部5周和11周（WK）肺后。 猴子收到低 H37RV剂量（30 CFU）在支气管中有颗粒状病变 感染后18周淋巴结。 病变表明低剂量 结核分枝杆菌H37RV至少在短期内通过 猿猴肺中的天然防御和更高的挑战 剂量的细菌会产生明显的组织反应 败血症传播的证据。 两个高剂量（150 CFU）Erdman 接受者猴子患上了广泛的肉芽肿性肺炎， 在 肝脏，肾脏和其他部位在7-9周内。 外观 肺炎和时间病程与产生的疾病大致相当 通过高剂量（> 106）H37RV。 2个低剂量的Erdman接种猴子 （15 CFU）挑战后9周在临床上保持正常，在19 WK的临床表现最少，但是纤维化肉芽肿 肺部病变扩散到其他组织。 我们得出结论 可以通过低剂量ERDMAN接种来确定慢性疾病 与H37RV相比，生产的病变分布更广泛 拉紧。 资金基础赠款，风险研究出版物迪迪尔PJ， Blanchard JL和Gormus BJ。 正常恒河猴中的肺结核 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。 低剂量结核分枝杆菌产生的慢性结核病 （Erdman）在恒河猴中。 Am J Soc Trop Med Hyg 59：361，1998。