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首页> 外文期刊>Parasitology >Molecular, biochemical characterization and assessment of immunogenic potential of cofactor-independent phosphoglycerate mutase against Leishmania donovani: a step towards exploring novel vaccine candidate
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Molecular, biochemical characterization and assessment of immunogenic potential of cofactor-independent phosphoglycerate mutase against Leishmania donovani: a step towards exploring novel vaccine candidate

机译：Cofactor-Wondovergerge Futase对Leishmania Donovani的分子，生化表征和评估免疫原性潜力：探索新型疫苗候选的一步

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Despite immense efforts, vaccine against visceral leishmaniasis has yet not been developed. Earlier our proteomic study revealed a novel protein, cofactor-independent phoshoglycerate mutase (LdiPGAM), an important enzyme in glucose metabolism, in T helper cells type 1 (Th1) stimulatory region of soluble Leishmania donovani antigen. In this study, LdiPGAM was biochemically and molecularly characterized and evaluated for its immunogenicity and prophylactic efficacy against L. donovani. Immunogenicity of recombinant LdiPGAM (rLdiPGAM) was initially assessed in na?ve hamsters immunized with it by analysing mRNA expression of inducible nitric oxide (NO) synthase (iNOS) and other Th1/T helper cells type 2 cytokines, which revealed an upregulation of Th1 cytokines along with iNOS. Immunogenicity of rLdiPGAM was further evaluated in lymphocytes of treated Leishmania-infected hamsters and peripheral blood mononuclear cells of Leishmania patients in clinical remission by various parameters, viz. lymphoproliferation assay and NO production (hamsters and patients) and levels of various cytokines (patients). rLdiPGAM induced remarkable Lymphoproliferative response and NO production in treated Leishmania-infected hamsters as well as in patients and increase in interferon gamma (IFN-γ), interleukin-12 (IL-12p40) responses in Leishmania patients in clinical remission. Vaccination with rLdiPGAM exerted considerable prophylactic efficacy (73%) supported by increase in mRNA expression of iNOS, IFN-γ and IL-12p40 with decrease in transforming growth factor beta and interleukin-10. Above results indicate the importance of rLdiPGAM protein as a potential vaccine candidate against visceral leishmaniasis.
机译：尽管努力，但尚未开发针对内脏利什曼病的疫苗。我们之前的蛋白质组学研究揭示了一种新的蛋白质，独立的官方偶联的磷糖糖蛋白酶（LDIPGAM），葡萄糖代谢中的一个重要酶，在溶扰Leishmania Donovani抗原的1型（Th1）刺激区。在本研究中，LDIPGAM生物化学和分子特征，并评估其免疫原性和对L. Donovani的预防性疗效。通过分析诱导型一氧化氮（NO）合成酶（INOS）的mRNA表达和其他TH1 / T辅助细胞2细胞因子，最初在用其免疫的NaαveHamsters中进行重组LDIPGAM（RLDIPGAM）的免疫原性。细胞因子与伊克斯一起。通过各种参数，在临床缓解的临床缓解治疗Leishmania感染的仓鼠和外周血单核细胞的淋巴细胞中，进一步评估RLDIPGAM的免疫原性。淋巴抑制剂测定，没有生产（仓鼠和患者）和各种细胞因子（患者）的水平。 RLDIPGAM诱导了淋巴抑制剂的反应显着，治疗Leishmania感染的仓鼠以及患者的干扰素γ（IL-12P40）在临床缓解中的干扰素γ（IL-12P40）反应中没有生产。通过RLDIPGAM的疫苗接种施加相当大的预防性疗效（73％），其通过在InOS，IFN-γ和IL-12P40的mRNA表达增加中支持，随着转化的生长因子β和白细胞介素-10的降低而受到降低。上述结果表明RLDIPGAM蛋白作为抵抗内脏Leishmaniaisis的潜在疫苗候选者的重要性。

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