Divergent effect of bacillus Calmette-Guerin (BCG) vaccination on Mycobacterium tuberculosis infection in highly related macaque species:: Implications for primate models in tuberculosis vaccine research
Divergent effect of bacillus Calmette-Guerin (BCG) vaccination on Mycobacterium tuberculosis infection in highly related macaque species:: Implications for primate models in tuberculosis vaccine research
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DOI：
10.1073/pnas.201404898
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发表时间：
2001-09-25
影响因子：
11.1
通讯作者：
Thomas, AW
中科院分区：
文献类型：
--
作者：
Langermans, JAM;Andersen, P;Thomas, AW
尽管广泛使用卡介苗疫苗，但结核分枝杆菌感染仍然是全球单一传染病导致死亡的主要原因。感染和疾病的复杂且往往旷日持久的动态，使得测试新型结核病疫苗的临床试验极其复杂。因此，临床前选择最有希望的候选药物是必要的。由于猕猴会患上一种与人类非常相似的疾病，除了小型动物模型外，它们还有可能提供重要的信息。为了评估恒河猴和食蟹猴作为结核病疫苗筛选者的相对优势，我们比较了卡介苗接种的效果和两种物种的感染过程。未接种疫苗的恒河猴和食蟹猴均发展为进行性疾病，伴有高水平的c反应蛋白、结核分枝杆菌特异性IgG，以及包括空化和干酪样坏死在内的广泛病理。卡尔梅特- guerin芽孢杆菌疫苗几乎完全保护食蟹虫的病理发展，与未接种疫苗的动物相比，肺部活菌数量减少了2倍。另一方面，恒河猴没有受到卡介苗芽孢杆菌的有效保护。接种疫苗的动物出现了实质性的病理，肺部集落形成单位的减少可以忽略不计。对这些密切相关的物种进行比较研究，可能有助于深入了解预防结核病的机制。
Despite the widespread use of bacillus Calmette-Guerin vaccination, Mycobacterium tuberculosis infection remains globally the leading cause of death from a single infectious disease. The complicated and often protracted dynamics of infection and disease make clinical trials to test new tuberculosis vaccines extremely complex. Preclinical selection of only the most promising candidates is therefore essential. Because macaque monkeys develop a disease very similar to humans, they have potential to provide important information in addition to small animal models. To assess the relative merits of rhesus and cynomolgus monkeys as screens for tuberculosis vaccines, we compared the efficacy of bacillus Calmette-Guerin vaccination and the course of infection in both species. Unvaccinated rhesus and cynomolgus monkeys both developed progressive disease with high levels of C-reactive protein, M. tuberculosis-specific IgG, and extensive pathology including cavitation and caseous necrosis. Bacillus Calmette-Guerin vaccination protected cynomolgus almost completely toward the development of pathology, reflected in a striking 2-log reduction in viable bacteria in the lungs compared with nonvaccinated animals. Rhesus, on the other hand, were not protected efficiently by the bacillus Calmette-Guerin. The vaccinated animals developed substantial pathology and had negligible reductions of colony-forming units in the lungs. Comparative studies in these closely related species are likely to provide insight into mechanisms involved in protection against tuberculosis.