Chagas disease is a chronic and potentially lethal disorder caused by the parasite Trypanosoma cruzi, and an effective treatment has not been developed for chronic Chagas disease. The objective of this study was to determine the effectiveness of a therapeutic DNA vaccine containing T. cruzi genes in dogs with experimentally induced Chagas disease through clinical, pathological, and immunological analyses. Infection of Beagle dogs with the H8 T. cruzi strain was performed intraperitoneally with 3500 metacyclic trypomastigotes/kg body weight. Two weeks after infection, plasmid DNA immunotherapy was administered thrice at 15-day intervals. The clinical (physical and cabinet studies), immunological (antibody and cytokine profiles and lymphoproliferation), and macro- and microscopic pathological findings were described. A significant increase in IgG and cell proliferation was recorded after immunotherapy, and the highest stimulation index (3.02) was observed in dogs treated with the pBCSSP4 plasmid. The second treatment with both plasmids induced an increase in IL-1, and the third treatment with the pBCSSP4 plasmid induced an increase in IL-6. The pBCSP plasmid had a good Th1 response regulated by high levels of IFN-gamma and TNF-alpha, whereas the combination of the two plasmids did not have a synergistic effect. Electrocardiographic studies registered lower abnormalities and the lowest number of individuals with abnormalities in each group treated with the therapeutic vaccine. Echocardiograms showed that the pBCSSP4 plasmid immunotherapy preserved cardiac structure and function to a greater extent and prevented cardiomegaly. The two plasmids alone controlled the infection moderately by a reduction in the inflammatory infiltrates in heart tissue. The immunotherapy was able to reduce the magnitude of cardiac lesions and modulate the cellular immune response; the pBCSP treatment showed a clear Th1 response; and pBCSSP4 induced a balanced Th1/Th2 immune response that prevented severe cardiac involvement. The pBCSSP4 plasmid had a better effect on most of the parameters evaluated in this study; therefore, this plasmid can be considered an optional treatment against Chagas disease in naturally infected dogs.

中文翻译：

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实验性克氏锥虫感染犬的DNA疫苗治疗。

南美锥虫病是由寄生虫克氏锥虫引起的一种慢性且可能致命的疾病，尚未开发出对慢性锥虫病的有效治疗方法。这项研究的目的是通过临床，病理学和免疫学分析，确定一种含有克氏锥虫基因的治疗性DNA疫苗在实验性诱发的南美锥虫病犬中的有效性。H8 T. cruzi感染比格犬腹膜内以每公斤体重3500个间环色鞭毛鞭毛体进行拉伤。感染后两周，每隔15天进行三次质粒DNA免疫治疗。描述了临床（物理和内阁研究），免疫学（抗体和细胞因子谱和淋巴增殖）以及宏观和微观病理学发现。免疫治疗后，IgG和细胞增殖显着增加，在用pBCSSP4质粒治疗的狗中观察到最高的刺激指数（3.02）。用两种质粒的第二次处理诱导IL-1增加，而用pBCSSP4质粒的第三种处理诱导IL-6增加。pBCSP质粒具有高水平的IFN-γ和TNF-α调节的Th1反应，两种质粒的组合没有协同作用。心电图研究显示，在用治疗性疫苗治疗的每组中，异常率较低，且异常个体的数量最少。超声心动图显示，pBCSSP4质粒免疫疗法在更大程度上保留了心脏结构和功能，并防止了心脏肥大。单独的两个质粒通过减少心脏组织中的炎症浸润来中等程度地控制感染。免疫疗法能够减少心脏病变的程度并调节细胞免疫反应。pBCSP处理显示出明显的Th1反应。pBCSSP4和pBCSSP4诱导了平衡的Th1 / Th2免疫反应，阻止了严重的心脏受累。pBCSSP4质粒对本研究中评估的大​​多数参数均具有较好的效果。因此，在自然感染的狗中，该质粒被认为是抗南美锥虫病的一种可选治疗方法。