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评价免疫应答,并分析利什曼原虫重组核糖体蛋白 L3 或 L5 疫苗接种对两种不同皮肤利什曼病小鼠模型的影响。

Evaluation of immune responses and analysis of the effect of vaccination of the Leishmania major recombinant ribosomal proteins L3 or L5 in two different murine models of cutaneous leishmaniasis.

机构信息

Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Nicolás Cabrera 1, Universidad Autónoma de Madrid, 28049 Madrid, Spain.

出版信息

Vaccine. 2013 Feb 18;31(9):1312-9. doi: 10.1016/j.vaccine.2012.12.071. Epub 2013 Jan 10.

DOI:10.1016/j.vaccine.2012.12.071
PMID:23313653
Abstract

Four new antigenic proteins located in Leishmania ribosomes have been characterized: S4, S6, L3 and L5. Recombinant versions of the four ribosomal proteins from Leishmania major were recognized by sera from human and canine patients suffering different clinical forms of leishmaniasis. The prophylactic properties of these proteins were first studied in the experimental model of cutaneous leishmaniasis caused by L. major inoculation into BALB/c mice. The administration of two of them, LmL3 or LmL5 combined with CpG-oligodeoxynucleotides (CpG-ODN) was able to protect BALB/c mice against L. major infection. Vaccinated mice showed smaller lesions and parasite burden compared to mice inoculated with vaccine diluent or vaccine adjuvant. Protection was correlated with an antigen-specific increased production of IFN-γ paralleled by a decrease of the antigen-specific IL-10 mediated response in protected mice relative to non-protected controls. Further, it was demonstrated that BALB/c mice vaccinated with recombinant LmL3 or LmL5 plus CpG-ODN were also protected against the development of cutaneous lesions following inoculation of L. braziliensis. Together, data presented here indicate that LmL3 or LmL5 ribosomal proteins combined with Th1 inducing adjuvants, may be relevant components of a vaccine against cutaneous leishmaniasis caused by distinct species.

摘要

四种位于利什曼原虫核糖体上的新抗原蛋白

S4、S6、L3 和 L5 已被鉴定。来自利什曼原虫的重组核糖体蛋白的版本被来自患有不同临床形式利什曼病的人类和犬类患者的血清识别。这些蛋白的预防性首先在由 L. major 接种到 BALB/c 小鼠引起的皮肤利什曼病的实验模型中进行了研究。其中两种蛋白,LmL3 或 LmL5 与 CpG-寡脱氧核苷酸(CpG-ODN)联合给药能够保护 BALB/c 小鼠免受 L. major 感染。与接种疫苗稀释剂或疫苗佐剂的小鼠相比,接种疫苗的小鼠显示出较小的病变和寄生虫负担。保护与抗原特异性 IFN-γ的增加产生相关,同时与未受保护的对照相比,受保护的小鼠中抗原特异性 IL-10 介导的反应降低。此外,证明用重组 LmL3 或 LmL5 加 CpG-ODN 接种的 BALB/c 小鼠也能够防止接种 L. braziliensis 后皮肤病变的发展。总之,本文提供的数据表明,LmL3 或 LmL5 核糖体蛋白与诱导 Th1 的佐剂结合,可能是针对不同物种引起的皮肤利什曼病的疫苗的相关成分。

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