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Evaluation of the protective efficacy of a Leishmania protein associated with distinct adjuvants against visceral leishmaniasis and in vitro immunogenicity in human cells.
Parasitology Research ( IF 1.8 ) Pub Date : 2020-06-13 , DOI: 10.1007/s00436-020-06752-x
Patrícia A F Ribeiro 1 , Daniel S Dias 1 , Daniela P Lage 1 , Débora V C Mendonça 1 , Danniele L Vale 1 , Fernanda F Ramos 1 , Lívia M Carvalho 2 , Ana Maria R S Carvalho 1 , Bethina T Steiner 3 , Marjorie C Roque 4 , João A Oliveira-da-Silva 1 , Jamil S Oliveira 5 , Grasiele S V Tavares 1 , Vívian T Martins 1 , Miguel A Chávez-Fumagalli 1 , Bruno M Roatt 2 , Ricardo L F Moreira 6 , Daniel Menezes-Souza 1, 7 , Mariana C Duarte 1, 7 , Mônica C Oliveira 4 , Ricardo A Machado-de-Ávila 3 , Antônio L Teixeira 1, 8 , Eduardo A F Coelho 1, 7
Affiliation  

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, a Leishmania protein 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 against Leishmania infantum infection. 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-γ, 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-γ levels in the cell supernatant. In conclusion, rLiHyE could be considered for future studies as a vaccine candidate against VL.



中文翻译:

评估与不同佐剂相关的利什曼原虫蛋白对内脏利什曼原虫病的保护作用以及人细胞的体外免疫原性。

内脏利什曼病(VL)的治疗存在问题,主要与药物的毒性和/或高成本有关。在这种情况下,迫切需要预防接种。在本研究中,评估了利什曼原虫蛋白LiHyE(最近被建议作为犬和人VL的抗原标记),评估了其在BALB / c小鼠中对婴儿利什曼原虫的免疫原性和保护功效。感染。此外,该蛋白还用于刺激治疗前后的VL患者以及健康受试者的外周血单核细胞(PBMC)。疫苗接种结果表明,与脂质体或皂苷相关的重组(rLiHyE)蛋白在小鼠中具有有效的保护作用,因为发现脾脏,肝脏,引流淋巴结和骨髓中的寄生虫负荷显着降低。寄生虫防护与Th1型细胞反应有关,因为除了低IL-4和IL-10产生外,还发现了高的IFN-γ,IL-12和GM-CSF水平。脂质体比皂苷具有更好的寄生虫学和免疫学保护作用。使用PBMC进行的实验显示,rLiHyE刺激了治疗的患者和健康受试者的细胞中的淋巴细胞增殖,以及细胞上清液中的高IFN-γ水平。总之,rLiHyE可以考虑作为VL的候选疫苗用于未来的研究。

更新日期:2020-06-13
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