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Differential Protective Efficacy of DNA Vaccines Expressing Secreted Proteins of Mycobacterium tuberculosis

机译：表达结核分枝杆菌分泌蛋白的DNA疫苗的差异保护作用

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The development of more-effective antituberculosis vaccines would assist in the control of the global problem of infection withMycobacterium tuberculosis. One recently devised vaccination strategy is immunization with DNA plasmids encoding individual microbial genes. Using the genes for the M. tuberculosis secreted proteins MPT64 (23 kDa), Ag85B (30 kDa), and ESAT-6 (6 kDa) as candidate antigens, DNA vaccines were prepared and tested for immunogenicity and protective efficacy in a murine model of aerosolized tuberculosis (TB). Intramuscular immunization with DNA-64 or DNA-85B resulted in the activation of CD4+ T cells, which produce gamma interferon (IFN-γ), and high titers of specific immunoglobulin G antibodies. Further, DNA-64 induced major histocompatibility complex class I-restricted CD8+cytotoxic T cells. The addition of a eukaryotic leader sequence tompt64 did not significantly increase the T-cell or antibody response. Each of the three DNA vectors stimulated a significant reduction in the level of M. tuberculosis infection in the lungs of mice challenged 4 weeks after immunization, but not to the levels resulting after immunization with Mycobacterium bovis BCG. The vaccines showed a consistent hierarchy of protection, with the most effective being Ag85B, followed by ESAT-6 and then MPT64. Coimmunization with the three vectors resulted in a greater degree of protection than that induced by any single vector. This protective efficacy was associated with the emergence of IFN-γ-secreting T cells earlier than in infected animals immunized with a control vector. The efficacy of these DNA vaccines suggests that multisubunit vaccination may contribute to future vaccine strategies against TB.
机译：开发更有效的抗结核疫苗将有助于控制结核分枝杆菌感染的全球性问题。最近设计的一种疫苗接种策略是用编码单个微生物基因的DNA质粒进行免疫。使用 M基因。结核分泌蛋白MPT64（23 kDa），Ag85B（30 kDa）和ESAT-6（6 kDa）作为候选抗原，制备了DNA疫苗，并在小鼠气雾化结核模型中测试了其免疫原性和保护功效（ TB）。用DNA-64或DNA-85B进行肌肉内免疫可激活CD4 + T细胞的活化，产生γ-干扰素（IFN-γ）和高滴度的特异性免疫球蛋白G抗体。此外，DNA-64诱导了主要的组织相容性复合体I类限制性CD8 + 细胞毒性T细胞。在 mpt64 中添加真核前导序列并没有显着增加T细胞或抗体应答。三种DNA载体中的每一种都刺激了 M水平的显着降低。免疫4周后，小鼠肺部感染结核杆菌，而牛分枝杆菌 BCG免疫后的水平未达到此水平。疫苗显示出一致的保护等级，最有效的是Ag85B，其次是ESAT-6，然后是MPT64。与任何单个载体诱导的保护相比，与这三个载体的共免疫产生的保护程度更高。与用对照载体免疫的感染动物相比，这种保护功效与分泌IFN-γ的T细胞的出现有关。这些DNA疫苗的功效表明，多亚基疫苗接种可能有助于未来针对结核病的疫苗策略。

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