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Evaluation of the protective efficacy of aLeishmaniaprotein associated with distinct adjuvants against visceral leishmaniasis and in vitro immunogenicity in human cells

机译:评价患有抗内脏Leishmaniaisis和体外免疫原性的不同佐剂与人细胞的体外免疫原性评价

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摘要

The treatment against visceral leishmaniasis (VL) presents problems, mainly related to the toxicity and/or high cost of the drugs. In this context, a prophylactic vaccination is urgently required. In the present study, aLeishmaniaprotein called LiHyE, which was suggested recently as an antigenic marker for canine and human VL, was evaluated regarding its immunogenicity and protective efficacy in BALB/c mice againstLeishmania infantuminfection. In addition, the protein was used to stimulate peripheral blood mononuclear cells (PBMCs) from VL patients before and after treatment, as well as from healthy subjects. Vaccination results showed that the recombinant (rLiHyE) protein associated with liposome or saponin induced effective protection in the mice, since significant reductions in the parasite load in spleen, liver, draining lymph nodes, and bone marrow were found. The parasitological protection was associated with Th1-type cell response, since high IFN-gamma, IL-12, and GM-CSF levels, in addition to low IL-4 and IL-10 production, were found. Liposome induced a better parasitological and immunological protection than did saponin. Experiments using PBMCs showed rLiHyE-stimulated lymphoproliferation in treated patients' and healthy subjects' cells, as well as high IFN-gamma levels in the cell supernatant. In conclusion, rLiHyE could be considered for future studies as a vaccine candidate against VL.
机译:针对内脏LeishManiaisis(VL)的治疗呈现出问题,主要与药物的毒性和/或高成本相关。在这种情况下,迫切需要预防性疫苗接种。在本研究中,在Balb / C小鼠的免疫原性和保护效应中,评估了最近被称为Lihye的含有Lihye的丙妥蛋白,这是犬和人VL的抗原性标志物。此外,蛋白质用于在治疗前后的VL患者以及治疗前后的外周血单核细胞(PBMC),以及来自健康受试者。疫苗接种结果表明,在小鼠中,与脂质体或皂苷诱导有效保护的重组(RliHye)蛋白,因为发现脾脏,肝脏,排水淋巴结和骨髓中寄生虫载荷的显着降低。发现,寄生虫学保护与Th1型细胞反应相关,因为发现除了低IL-4和IL-10生产之外,高IFN-Gamma,IL-12和GM-CSF水平。脂质体诱导比皂苷更好的寄生虫和免疫保护。使用PBMCs的实验显示患者和健康受试者细胞中的Rlihye刺激的淋巴抑制化,以及细胞上清液中的高IFN-Gamma水平。总之,rlihye可以被认为是未来的研究作为反对VL的疫苗候选者。

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