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杜氏利什曼原虫二肽基羧肽酶:一种针对实验性内脏利什曼病的潜在疫苗分子。

Dipeptidylcarboxypeptidase of Leishmania donovani: A potential vaccine molecule against experimental visceral leishmaniasis.

机构信息

Division of Biochemistry and Structural Biology, CSIR- Central Drug Research Institute, Jankipuram Vistar, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

Division of Biochemistry and Structural Biology, CSIR- Central Drug Research Institute, Jankipuram Vistar, Lucknow 226031, India.

出版信息

Cell Immunol. 2022 May;375:104529. doi: 10.1016/j.cellimm.2022.104529. Epub 2022 Apr 26.

DOI:10.1016/j.cellimm.2022.104529
PMID:35500334
Abstract

Visceral leishmaniasis is one of the deadliest parasitic diseases in the world. In the absence of an efficient and cost-effective drugs, development of an effective vaccine is the need of the day. In spite of several efforts, a successful vaccine against the disease has been elusive. We have evaluated immunoprophylactic efficacy of recombinant dipeptidycarboxypeptidase (rLdDCP), predominantly expressed in amastigotes, in chronic hamster model. rLdDCP induced in vitro lymphoproliferation and NO production in cured hamsters. Immunization with rLdDCP alone, or with BCG, caused significant reduction in parasite load suggesting strong protective response. The molecule also augmented the CMI response as depicted by an increased lymphocyte proliferation, NO production, DTH responses and increased levels of IgG2 in immunized hamsters. The vaccinated hamsters exhibited a surge in IFN-γ, TNF-α, IL-12 and iNOS levels but down-regulation of IL-10 and IL-4. Thus, the results suggest the potentiality of the rLdDCP as a strong candidate vaccine.

摘要

内脏利什曼病是世界上最致命的寄生虫病之一。由于缺乏高效且经济有效的药物,因此开发有效的疫苗是当务之急。尽管进行了多次努力,但针对该疾病的成功疫苗仍难以实现。我们已经在慢性仓鼠模型中评估了主要在无鞭毛体中表达的重组二肽羧基肽酶(rLdDCP)的免疫预防功效。rLdDCP 在已治愈的仓鼠中诱导体外淋巴细胞增殖和 NO 产生。单独用 rLdDCP 或用卡介苗(BCG)免疫可显著降低寄生虫载量,表明具有强大的保护作用。该分子还增强了细胞介导的免疫反应,表现为淋巴细胞增殖、NO 产生、迟发型超敏反应和免疫仓鼠中 IgG2 水平的增加。接种疫苗的仓鼠表现出 IFN-γ、TNF-α、IL-12 和 iNOS 水平的激增,但 IL-10 和 IL-4 的下调。因此,这些结果表明 rLdDCP 作为一种强有力的候选疫苗具有潜力。

相似文献

1
Dipeptidylcarboxypeptidase of Leishmania donovani: A potential vaccine molecule against experimental visceral leishmaniasis.杜氏利什曼原虫二肽基羧肽酶:一种针对实验性内脏利什曼病的潜在疫苗分子。
Cell Immunol. 2022 May;375:104529. doi: 10.1016/j.cellimm.2022.104529. Epub 2022 Apr 26.
2
Immunological characterization of rLdTCP1γ for its prophylactic potential against visceral leishmaniasis in hamster model.rLdTCP1γ 的免疫特性及其在仓鼠模型中预防内脏利什曼病的潜力。
Mol Immunol. 2022 Jan;141:33-42. doi: 10.1016/j.molimm.2021.11.009. Epub 2021 Nov 16.
3
Elongation factor-2, a Th1 stimulatory protein of Leishmania donovani, generates strong IFN-γ and IL-12 response in cured Leishmania-infected patients/hamsters and protects hamsters against Leishmania challenge.延伸因子-2,杜氏利什曼原虫的 Th1 刺激蛋白,在治愈的利什曼原虫感染患者/仓鼠中产生强烈的 IFN-γ 和 IL-12 反应,并保护仓鼠免受利什曼原虫的挑战。
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4
Characterization of glycolytic enzymes--rAldolase and rEnolase of Leishmania donovani, identified as Th1 stimulatory proteins, for their immunogenicity and immunoprophylactic efficacies against experimental visceral leishmaniasis.对利什曼原虫的糖酵解酶--r 醛缩酶和 r 烯醇酶的特性进行研究,这两种酶被鉴定为 Th1 刺激性蛋白,用于评估其针对实验性内脏利什曼病的免疫原性和免疫预防效果。
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PLoS One. 2014 Sep 30;9(9):e108556. doi: 10.1371/journal.pone.0108556. eCollection 2014.
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Leishmania donovani serine protease encapsulated in liposome elicits protective immunity in experimental visceral leishmaniasis.脂质体包裹的杜氏利什曼原虫丝氨酸蛋白酶诱导实验性内脏利什曼病的保护性免疫。
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Recombinant NAD-dependent SIR-2 protein of Leishmania donovani: immunobiochemical characterization as a potential vaccine against visceral leishmaniasis.杜氏利什曼原虫重组NAD依赖型SIR-2蛋白:作为抗内脏利什曼病潜在疫苗的免疫生化特性
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115 kDa serine protease confers sustained protection to visceral leishmaniasis caused by Leishmania donovani via IFN-γ induced down-regulation of TNF-α mediated MMP-9 activity.115 kDa 丝氨酸蛋白酶通过 IFN-γ 诱导的 TNF-α 介导体外 MMP-9 活性下调,为内脏利什曼病(由利什曼原虫引起)提供持续保护。
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Evaluation of Leishmania donovani protein disulfide isomerase as a potential immunogenic protein/vaccine candidate against visceral Leishmaniasis.评价杜氏利什曼原虫蛋白二硫键异构酶作为一种针对内脏利什曼病的潜在免疫原性蛋白/疫苗候选物。
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