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婴儿利什曼原虫:用I型半胱氨酸蛋白酶C末端延伸进行初免-加强免疫接种在BALB/c小鼠中显示出1型和2型免疫特征。

Leishmania infantum: prime boost vaccination with C-terminal extension of cysteine proteinase type I displays both type 1 and 2 immune signatures in BALB/c mice.

作者信息

Rafati Sima, Zahedifard Farnaz, Azari Mahnaz Kakeh, Taslimi Yasaman, Taheri Tahereh

机构信息

Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Exp Parasitol. 2008 Mar;118(3):393-401. doi: 10.1016/j.exppara.2007.10.004. Epub 2007 Oct 13.

Abstract

The aims of current study are to describe the immunogenicity and protective efficacy of prime boost vaccine using C-terminal extension (CTE) of cysteine proteinase type I of Leishmania infantum in BALB/c mice. Group I as vaccinated group primed with 100 microg of pcDNA-CTE and 3 weeks later boosted with combination of 30 microg rCTE, 50 microg of CpG and Montanide 720. Groups II and III were served as control groups. Although, this vaccination regimen did not protect mice against the infectious challenge but it was highly immunogenic. IgG2a has been raised strongly against rCTE in contrast to IgG1 and remains high at every time point under study. By analysis of CTE synthetic peptides (CTE100) before challenge, both IgG1 and IgG2a were produced and for all overlapping synthetic peptides (CTE 1-8) IgG1 raised significantly. This statue is changed at 7 weeks after challenge and only CTE2 and CTE3 have shown to induce considerable amount of IgG1. In all groups, the level of IL-5 started to increase with high concentration shortly passing only 3 weeks after infectious challenge. In compare with two control groups, the vaccinated group produced significantly higher level of IL-5 at 7 weeks post-infection. The parasite burden of all groups is similar at 4 weeks post-challenge in both liver and spleen. In contrast, at 8 weeks post challenge, the spleen of the vaccinated group showed significantly higher level of parasite load in compare with two control groups. This study demonstrated that immunization with CTE display both type 1 and 2 immune signatures in experimental murine model of L. infantum infection.

摘要

本研究的目的是描述在BALB/c小鼠中使用婴儿利什曼原虫I型半胱氨酸蛋白酶C末端延伸区(CTE)的初免-加强疫苗的免疫原性和保护效果。第一组作为接种组,用100微克的pcDNA-CTE进行初免,3周后用30微克重组CTE(rCTE)、50微克CpG和Montanide 720的组合进行加强免疫。第二组和第三组作为对照组。尽管这种疫苗接种方案不能保护小鼠免受感染攻击,但它具有高度免疫原性。与IgG1相比,IgG2a针对rCTE的反应强烈升高,并且在研究的每个时间点都保持在较高水平。在攻击前分析CTE合成肽(CTE100)时,产生了IgG1和IgG2a,并且对于所有重叠合成肽(CTE 1-8),IgG1显著升高。这种情况在攻击后7周发生变化,只有CTE2和CTE3显示能诱导产生相当数量的IgG1。在所有组中,感染攻击仅3周后,IL-5水平开始迅速升高。与两个对照组相比,接种组在感染后7周产生的IL-5水平显著更高。在攻击后4周,所有组在肝脏和脾脏中的寄生虫负荷相似。相反,在攻击后8周,与两个对照组相比,接种组脾脏中的寄生虫负荷水平显著更高。本研究表明,在婴儿利什曼原虫感染的实验小鼠模型中,用CTE免疫呈现出1型和2型免疫特征。

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