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首页> 外文期刊>Parasitology >High-through identification of T cell-specific phage-exposed mimotopes using PBMCs from tegumentary leishmaniasis patients and their use as vaccine candidates against Leishmania amazonensis infection
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High-through identification of T cell-specific phage-exposed mimotopes using PBMCs from tegumentary leishmaniasis patients and their use as vaccine candidates against Leishmania amazonensis infection

机译：使用来自Tegumentary Leishmaniaisis患者的PBMC的T细胞特异性噬菌体暴露的模拟物的高分辨率鉴定及其作为针对Leishmania Amazonensis感染的疫苗候选者

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摘要

In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.
机译：在目前的研究中，通过使用来自未经处理的外周血单核细胞（PBMC）的外周血单核细胞（PBMC）的免疫刺激，通过生物淘选循环选择作为针对Tegumentary Leishmaniaisis（T1）的靶标的靶标的模拟物。并治疗T1患者和健康受试者。在体外培养物中评价关于其特异性干扰素-γ（IFN-γ）和白细胞介素-4（IL-4）产生的克隆，并计算选择性和特异性值，并选择呈现最佳结果的选择性和特异性值体内实验。鉴定了两个克隆，即A4和A8，并用于来自BALB / C小鼠的免疫方案，以防止Leishmania Amazonensis感染。结果表明，疫苗接种后产生的偏振Th1反应，基于IFN-γ，IL-2，IL-12，肿瘤坏死因子-α（TNF-α）和粒细胞 - 巨噬细胞刺激因子（GM- CSF）;这与特异性IL-4，IL-10和免疫球蛋白G1（IgG1）抗体的产生相关。与对照相比，接种疫苗的小鼠在受感染的组织和不同器官中寄生物载体的显着降低。总之，我们提出了一种识别能够诱导来自TL患者和健康受试者的PBMC中的新模拟物的策略，并成功地用于防止L.Axazonensis感染。

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