Baldwin S L, D'Souza C, Roberts A D, Kelly B P, Frank A A, Lui M A, Ulmer J B, Huygen K, McMurray D M, Orme I M
Mycobacteria Research Laboratories, Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523, USA.
Infect Immun. 1998 Jun;66(6):2951-9. doi: 10.1128/IAI.66.6.2951-2959.1998.
The results of this study provide the first evidence that two completely separate vaccine approaches, one based on a subunit vaccine consisting of a mild adjuvant admixed with purified culture filtrate proteins and enhanced by the cytokine interleukin-2 and the second based on immunization with DNA encoding the Ag85A protein secreted by Mycobacterium tuberculosis, could both prevent the onset of caseating disease, which is the hallmark of the guinea pig aerogenic infection model. In both cases, however, the survival of vaccinated guinea pigs was shorter than that conferred by Mycobacterium bovis BCG, with observed mortality of these animals probably due to consolidation of lung tissues by lymphocytic granulomas. An additional characteristic of these approaches was that neither induced skin test reactivity to commercial tuberculin. These data thus provide optimism that development of nonliving vaccines which can generate long-lived immunity approaching that conferred by the BCG vaccine is a feasible goal.
本研究结果首次证明，两种完全不同的疫苗接种方法，一种基于由温和佐剂与纯化培养滤液蛋白混合而成的亚单位疫苗，并通过细胞因子白细胞介素-2增强；另一种基于用编码结核分枝杆菌分泌的Ag85A蛋白的DNA进行免疫接种，这两种方法都可以预防干酪样疾病的发生，而干酪样疾病是豚鼠气溶胶感染模型的标志。然而，在这两种情况下，接种疫苗的豚鼠的存活时间都比牛分枝杆菌卡介苗接种后的豚鼠存活时间短，这些动物的观察到的死亡率可能是由于淋巴细胞肉芽肿导致肺组织实变。这些方法的另一个特点是，它们都不会诱导对商用结核菌素的皮肤试验反应。因此，这些数据让人乐观地认为，开发能够产生接近卡介苗所赋予的长期免疫力的非活性疫苗是一个可行的目标。
