Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Vaccine. 2012 Feb 21;30(9):1572-82. doi: 10.1016/j.vaccine.2011.12.114. Epub 2012 Jan 11.
Bacillus-Calmette-Guerin (BCG), the only human tuberculosis vaccine, primes a partially protective immune response against Mycobacterium tuberculosis infection in humans and animals. In guinea pigs, BCG vaccination slows the progression of disease and reduces the severity of necrotic granulomas, which harbor a population of drug-tolerant bacilli. The objective of this study was to determine if reducing disease severity by BCG vaccination of guinea pigs prior to M. tuberculosis challenge enhanced the efficacy of combination drug therapy. At 20 days of infection, treatment of vaccinated and non-vaccinated animals with rifampin, isoniazid, and pyrizinamide (RHZ) was initiated for 4 or 8 weeks. On days 50, 80 and 190 of infection (10 weeks after drug were withdrawn), treatment efficacy was evaluated by quantifying clinical condition, bacterial loads, lesion severity, and dynamic changes in peripheral blood and lung leukocyte numbers by flow cytometry. In a separate, long-term survival study, treatment efficacy was evaluated by determining disease reactivation frequency post-mortem. BCG vaccination alone delayed pulmonary and extra-pulmonary disease progression, but failed to prevent dissemination of bacilli and the formation of necrotic granulomas. Drug therapy either alone or in combination with BCG, was more effective at lessening clinical disease and lesion severity compared to control animals or those receiving BCG alone. Fewer residual lesions in BCG vaccinated and drug treated animals, equated to a reduced frequency of reactivation disease and improvement in survival even out to 500 days of infection. The combining of BCG vaccination and drug therapy was more effective at resolving granulomas such that fewer animals had evidence of residual infection and thus less reactivation disease.
卡介苗（BCG）是唯一的人类结核病疫苗，可在人类和动物中引发针对结核分枝杆菌感染的部分保护免疫反应。在豚鼠中，BCG 疫苗接种可减缓疾病进展并减轻坏死性肉芽肿的严重程度，这些肉芽肿中存在一群耐药物的杆菌。本研究的目的是确定在结核分枝杆菌攻击前通过 BCG 疫苗接种来减轻豚鼠疾病的严重程度是否可以增强联合药物治疗的效果。在感染后 20 天，对接种和未接种疫苗的动物用利福平、异烟肼和吡嗪酰胺（RHZ）进行 4 或 8 周的治疗。在感染第 50、80 和 190 天（停药后 10 周），通过流式细胞术定量评估临床状况、细菌负荷、病变严重程度以及外周血和肺白细胞数量的动态变化来评估治疗效果。在单独的长期生存研究中，通过确定死后疾病复发的频率来评估治疗效果。BCG 疫苗接种单独延迟了肺内和肺外疾病的进展，但未能阻止杆菌的传播和坏死性肉芽肿的形成。与对照组或仅接受 BCG 接种的动物相比，单独或联合使用药物治疗在减轻临床疾病和病变严重程度方面更有效。BCG 接种和药物治疗的动物中残留病变较少，意味着疾病复发的频率降低，感染 500 天的生存率提高。BCG 疫苗接种和药物治疗的联合使用在解决肉芽肿方面更有效，因此更少的动物有残留感染的证据，因此疾病复发的可能性更低。
