Drug treatment combined with BCG vaccination reduces disease reactivation in guinea pigs infected with Mycobacterium tuberculosis
Drug treatment combined with BCG vaccination reduces disease reactivation in guinea pigs infected with Mycobacterium tuberculosis
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DOI：
10.1016/j.vaccine.2011.12.114
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发表时间：
2012-02-21
期刊：
影响因子：
5.5
通讯作者：
Basaraba, Randall J.
中科院分区：
文献类型：
--
作者：
Shang, Shaobin;Shanley, Crystal A.;Basaraba, Randall J.
卡介苗 (BCG) 是唯一的人类结核病疫苗，可在人类和动物体内引发针对结核分枝杆菌感染的部分保护性免疫反应。在豚鼠中，卡介苗疫苗接种可以减缓疾病的进展并降低坏死性肉芽肿的严重程度，坏死性肉芽肿中含有大量耐药杆菌。本研究的目的是确定在结核分枝杆菌攻击之前通过给豚鼠接种卡介苗来降低疾病严重程度是否可以增强联合药物治疗的功效。感染第 20 天时，开始用利福平、异烟肼和吡嗪酰胺 (RHZ) 对已接种疫苗和未接种疫苗的动物进行 4 或 8 周的治疗。在感染第50，80和190天（停药后10周），通过流式细胞术量化临床状况、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。在一项单独的长期生存研究中，通过确定死后疾病再激活频率来评估治疗效果。单独接种卡介苗可延缓肺部和肺外疾病的进展，但无法阻止杆菌传播和坏死肉芽肿的形成。与对照动物或单独接受卡介苗的动物相比，单独或与卡介苗联合药物治疗在减轻临床疾病和病变严重程度方面更有效。接种 BCG 疫苗和药物治疗的动物中残留病变较少，相当于疾病再激活频率降低，甚至感染 500 天后生存率提高。卡介苗疫苗接种和药物治疗相结合可以更有效地解决肉芽肿，从而减少有残留感染证据的动物，从而减少再激活疾病。 (C) 2012 Elsevier Ltd. 保留所有权利。
Bacillus-CaImette-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 On days 50,80 and 190 of infection (10 weeks after drug were withdrawn), treatment efficacy was evaluated by quantifying clinical condition, bacterial loads, lesion severity, and dynamic changes in peripheral blood and lung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. (C) 2012 Elsevier Ltd. All rights reserved.