Chagas disease, caused by the hemoflagelate parasite Trypanosoma cruzi , is one of the most prevalent endemic parasitoses, affecting 7–8 million people. Due to the complexity of the infection, no vaccines are available at present. The extraordinary adjuvant capacity of bacille Calmette–Guérin (BCG) was explored in this work to develop a vaccine candidate to protect against T. cruzi infection using the recombinant BCG (rBCG) vaccine platform. Three antigens of the parasite corresponding to the N and C terminal fragments of the enzyme trans‐sialidase (NT‐TS and CT‐TS, respectively) and a fragment of the cruzipain enzyme (CZf) were cloned into the vectors pUS997 and pUS2000 and transformed into the BCG Pasteur strain. In vaccinated mice, rBCG expressing NT‐TS in pUS2000 plasmid provided the highest protection and the lowest parasitemia after challenging BALB/c mice with a 50% lethal dose of parasites. When mice vaccinated with pUS2000‐NT‐TS were challenged with a 100% lethal dose of parasite, high levels of protection were also obtained, together with a low degree of cardiac lesions 120 days after infection. In immunized mice with pUS2000‐NT‐TS/rBCG clone, the proliferation of CD4⁺ cells from splenocytes stimulated with the TS antigen was significant; this stimulation increased interferon (IFN)‐γ and interleukin (IL)‐17 within CD4⁺ T lymphocytes (LTCD4⁺) cells and IFN‐γ and CD107 expression within LTCD8⁺ cells. Therefore, pUS2000‐NT‐TS/rBCG conferred high levels of protection, which correlated with an immune response orientated towards a T helper type 1 (Th1)/Th17 profile, together with an LTC‐specific response, indicating that rBCG is a promising platform to develop vaccines against T. cruzi .

中文翻译：

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重组牛分枝杆菌 BCG 是开发针对克氏锥虫感染的疫苗的有前途的平台。

由血鞭毛虫克氏锥虫引起的恰加斯病是最普遍的地方性寄生虫病之一，影响了 7-800万人。由于感染的复杂性，目前没有可用的疫苗。在这项工作中探索了卡介苗 (BCG) 非凡的佐剂能力，以开发一种候选疫苗来预防克氏锥虫使用重组卡介苗 (rBCG) 疫苗平台进行感染。将对应于转唾液酸酶 N 和 C 末端片段（分别为 NT-TS 和 CT-TS）和 cruzipain 酶（CZf）片段的三种寄生虫抗原克隆到载体 pUS997 和 pUS2000 中并转化进入 BCG 巴斯德菌株。在接种疫苗的小鼠中，在用 50% 致死剂量的寄生虫攻击 BALB/c 小鼠后，在 pU​​S2000 质粒中表达 NT-TS 的 rBCG 提供了最高的保护和最低的寄生虫血症。当接种 pUS2000-NT-TS 的小鼠接受 100% 致死剂量的寄生虫攻击时，也获得了高水平的保护，以及感染后 120 天的低程度心脏病变。在 pUS2000-NT-TS/rBCG 克隆免疫小鼠中，CD4 ⁺来自用TS抗原刺激的脾细胞的细胞是显着的；这种刺激增加干扰素（IFN）-γ和白介素（IL）-17 CD4 + T淋巴细胞（LTCD4内⁺ LTCD8内）细胞和IFN-γ和CD107表达⁺细胞。因此，pUS2000-NT-TS/rBCG 提供了高水平的保护，这与针对 T 辅助型 1 (Th1)/Th17 谱的免疫反应以及 LTC 特异性反应相关，表明 rBCG 是一个有前途的平台开发针对克氏锥虫的疫苗。