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用婴儿利什曼原虫酸性核糖体P0蛋白加CpG寡脱氧核苷酸进行疫苗接种可诱导C57BL/6小鼠对皮肤利什曼病产生保护作用,但不能预防BALB/c小鼠的进行性疾病。

Vaccination with the Leishmania infantum acidic ribosomal P0 protein plus CpG oligodeoxynucleotides induces protection against cutaneous leishmaniasis in C57BL/6 mice but does not prevent progressive disease in BALB/c mice.

作者信息

Iborra Salvador, Carrión Javier, Anderson Charles, Alonso Carlos, Sacks David, Soto Manuel

机构信息

Centro de Biología Molecular "Severo Ochoa," Universidad Autónoma de Madrid, 28049 Madrid, Spain.

出版信息

Infect Immun. 2005 Sep;73(9):5842-52. doi: 10.1128/IAI.73.9.5842-5852.2005.

Abstract

We have examined the efficacy of the administration in mice of a molecularly defined vaccine based on the Leishmania infantum acidic ribosomal protein P0 (rLiP0). Two different challenge models of murine cutaneous leishmaniasis were used: (i) subcutaneous inoculation of L. major parasites in susceptible BALB/c mice (a model widely used for vaccination analysis) and (ii) the intradermal inoculation of a low infective dose in resistant C57BL/6 mice (a model that more accurately reproduces the L. major infection in natural reservoirs and in human hosts). First, we demonstrated that C57BL/6 mice vaccinated with LiP0-DNA or rLiP0 protein plus CpG oligodeoxynucleotides (ODN) were protected against the development of dermal pathology and showed a reduction in the parasite load. This protection was associated with production of gamma interferon (IFN-gamma) in the dermal site. Secondly, we showed that immunization with rLiP0 plus CpG ODN is able to induce only partial protection in BALB/c, since these mice finally developed a progressive disease. Further, we demonstrated that LiP0 vaccination induces a Th1 immunological response in both strains of mice. In both cases, the antibodies against LiP0 were predominantly of the immunoglobulin G2a isotype, which was correlated with an rLiP0-stimulated production of IFN-gamma in draining lymph nodes. Finally, we demonstrated that LiP0 vaccination does not prevent the Th2 response induced by L. major infection in BALB/c mice. Taken together, these data indicate that the BALB/c model of cutaneous leishmaniasis may undervalue the potential efficacy of some vaccines based on defined proteins, making C57BL/6 a suitable alternative model to test vaccine candidates.

摘要

我们研究了基于婴儿利什曼原虫酸性核糖体蛋白P0(rLiP0)的分子明确疫苗对小鼠的接种效果。使用了两种不同的小鼠皮肤利什曼病攻毒模型:(i)在易感的BALB/c小鼠中皮下接种硕大利什曼原虫(一种广泛用于疫苗接种分析的模型),以及(ii)在抗性C57BL/6小鼠中皮内接种低感染剂量(一种更准确模拟自然宿主和人类宿主中硕大利什曼原虫感染的模型)。首先,我们证明接种LiP0-DNA或rLiP0蛋白加CpG寡脱氧核苷酸(ODN)的C57BL/6小鼠可免受皮肤病理发展的影响,并显示寄生虫负荷降低。这种保护与皮肤部位γ干扰素(IFN-γ)的产生有关。其次,我们表明用rLiP0加CpG ODN免疫仅能在BALB/c小鼠中诱导部分保护,因为这些小鼠最终会发展为进行性疾病。此外,我们证明LiP0疫苗接种在两种小鼠品系中均诱导Th1免疫反应。在这两种情况下,针对LiP0的抗体主要是免疫球蛋白G2a同种型,这与引流淋巴结中rLiP0刺激的IFN-γ产生相关。最后,我们证明LiP0疫苗接种不能预防BALB/c小鼠中硕大利什曼原虫感染诱导的Th2反应。综上所述,这些数据表明皮肤利什曼病的BALB/c模型可能低估了一些基于特定蛋白质的疫苗的潜在效力,使得C57BL/6成为测试候选疫苗的合适替代模型。

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