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用重组杜氏利什曼原虫γ-谷氨酰半胱氨酸合成酶融合蛋白进行疫苗接种可预防杜氏利什曼原虫感染。

Vaccination with recombinant Leishmania donovani gamma-glutamylcysteine synthetase fusion protein protects against L. donovani infection.

作者信息

Henriquez F L, Campbell S A, Roberts C W, Mullen A B, Burchmore R, Carter K C

机构信息

School of Science, University of the West of Scotland, Paisley, UK.

出版信息

J Parasitol. 2010 Oct;96(5):929-36. doi: 10.1645/GE-2360.1. Epub 2010 Apr 17.

Abstract

Visceral leishmaniasis presents a serious health threat in many parts of the world. There is, therefore, an urgent need for an approved vaccine for clinical use to protect against infection. In this study, the ability of recombinant Leishmania donovani gamma-glutamyl cysteine synthetase protein (LdγGCS) alone or incorporated into a non-ionic surfactant vesicle (NIV) delivery system to protect against L. donovani infection was evaluated in a BALB/c mouse model. Immunization with LdγGCS alone or LdγGCS-NIV induced specific IgG1 and IgG2a antibodies compared to controls, with LdγGCS-NIV inducing significantly higher titers of both antibody classes (P < 0.05). Both formulations induced similar increases in splenocyte IFN-γ production following ex vivo antigen stimulation with LdγGCS compared with cells from control mice (P < 0.05). Similar levels of protection against infection were induced by LdγGCS alone and LdγGCS-NIV, based on their ability to suppress liver parasite burdens compared to control values (P < 0.01), indicating that using a carrier system did not enhance the protective responses induced by the recombinant protein. The results of this study indicate that LdγGCS may be a useful component in a vaccine against L. donovani.

摘要

内脏利什曼病在世界许多地区构成严重的健康威胁。因此,迫切需要一种经批准可用于临床的疫苗来预防感染。在本研究中,在BALB/c小鼠模型中评估了重组杜氏利什曼原虫γ-谷氨酰半胱氨酸合成酶蛋白(LdγGCS)单独或掺入非离子表面活性剂囊泡(NIV)递送系统预防杜氏利什曼原虫感染的能力。与对照组相比,单独用LdγGCS或LdγGCS-NIV免疫诱导了特异性IgG1和IgG2a抗体,LdγGCS-NIV诱导的两种抗体类别的滴度均显著更高(P < 0.05)。与对照小鼠的细胞相比,在用LdγGCS进行体外抗原刺激后,两种制剂诱导的脾细胞IFN-γ产生的增加相似(P < 0.05)。基于LdγGCS单独和LdγGCS-NIV与对照值相比抑制肝脏寄生虫负荷的能力,它们诱导了相似水平的抗感染保护作用(P < 0.01),表明使用载体系统并未增强重组蛋白诱导的保护反应。本研究结果表明,LdγGCS可能是抗杜氏利什曼原虫疫苗中的一种有用成分。

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