Improved immunotherapy for pulmonary tuberculosis with Mycobacterium vaccae

G.M. Bahr , M.A. Shaaban , M. Gabriel , B. Al-Shimali , Z. Siddiqui , T.D. Chugh , F.M. Denath , A. Shahin , K. Behbehani , L. Chedid , G.A.W. Rook , J.L. Stanford
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引用次数: 47

Abstract

We previously demonstrated that a single intradermal injection of 109 irradiation-killed M. vaccae, given 1 month after starting chemotherapy, caused significant changes in responses to mycobacterial antigens. Amongst 38 patients with pulmonary tuberculosis, 29% had lymphocytes responding to common mycobacterial antigens after the injection, compared with only 11 % of 49 similar patients after an injection of saline (p < 0.03).

To increase the proportion of responders to these antigens, six modifications of the potentially immunotherapeutic injection, randomized with injections of saline, have been assessed by biochemical, clinical, haematological, immunological and radiological criteria.

Subsequent lymphocyte proliferation to mycobacterial antigens enabled the modifications to be ranked in order of efficacy. Tuberculin plus murabutide plus 109 irradiated M. vaccae (36% of 25), an autoclaved preparation of 109M. vaccae (45% of 22), and 2 x 109 irradiated M. vaccae (75% of 12) were the most effective. Antibody responses in several IgG subclasses to mycobacteria, but not streptococci, were also significantly increased by the most effective modifications over the 8 weeks following injection.

Detailed radiological study showed that use of the autoclaved bacilli was followed by a delay in clearing of consolidation, but by better closing of cavities than was found in the control group, suggesting enhanced, or altered, immunological activity around the lesions.

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母牛分枝杆菌感染肺结核的改进免疫疗法
我们之前证明,在化疗开始1个月后,单次皮内注射109照射杀死的母牛分枝杆菌,可引起对分枝杆菌抗原反应的显着变化。在38例肺结核患者中,29%的患者在注射后淋巴细胞对常见的分枝杆菌抗原有反应,而在49例类似患者中,注射生理盐水后只有11% (p <0.03)。为了增加对这些抗原的应答比例,对六种可能具有免疫治疗作用的注射剂进行了修改,随机注射生理盐水,并通过生化、临床、血液学、免疫学和放射学标准进行了评估。随后淋巴细胞对分枝杆菌抗原的增殖使这些修饰按照疗效排序。结核菌素+穆拉肽+ 109辐照母牛分枝杆菌(占25的36%),一种109M的高压灭菌制剂。2 × 109辐照的母牛分枝杆菌(12例中的75%)最有效。在注射后的8周内,通过最有效的修饰,几种IgG亚类对分枝杆菌(但不包括链球菌)的抗体反应也显著增加。详细的放射学研究显示,使用高压灭菌杆菌后,实变清除延迟,但比对照组更好地关闭了空腔,这表明病变周围的免疫活性增强或改变。
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