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接种重组嵌合抗原 recNcMIC3-1-R 可在感染新生隐球菌的怀孕小鼠模型中诱导非保护性 Th2 型免疫反应。

Vaccination with the recombinant chimeric antigen recNcMIC3-1-R induces a non-protective Th2-type immune response in the pregnant mouse model for N. caninum infection.

机构信息

Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland.

出版信息

Vaccine. 2012 Oct 12;30(46):6588-94. doi: 10.1016/j.vaccine.2012.08.024. Epub 2012 Aug 29.

DOI:10.1016/j.vaccine.2012.08.024
PMID:22940381
Abstract

The major route of transmission of Neospora caninum in cattle is transplacentally from an infected cow to its progeny. Therefore, a vaccine should be able to prevent both the horizontal transmission from contaminated food or water and the vertical transmission. We have previously shown that a chimeric vaccine composed of predicted immunogenic epitopes of NcMIC3, NcMIC1 and NcROP2 (recNcMIC3-1-R) significantly reduced the cerebral infection in BALB/c mice. In this study, mice were first vaccinated, then mated and pregnant mice were challenged with 2×10(6)N. caninum tachyzoites at day 7-9 of pregnancy. Partial protection was only observed in the mice vaccinated with a tachyzoite crude protein extract but no protection against vertical transmission or cerebral infection in the dams was observed in the group vaccinated with recNcMIC3-1-R. Serological and cytokine analysis showed an overall lower cytokine level in sera associated with a dominant IL-4 expression and high IgG1 titers. Thus, the Th2-type immune response observed in the pregnant mice was not protective against experimental neosporosis, in contrary to the mixed Th1-/Th2-type immune response observed in the non-pregnant mouse model. These results demonstrate that the immunomodulation that occurs during pregnancy was not favorable for the protection against N. caninum infection conferred by vaccination with recNcMIC3-1-R.

摘要

刚地弓形虫在牛中的主要传播途径是通过受感染的母牛经胎盘垂直传播给后代。因此,疫苗应该能够预防水平传播(来自受污染的食物或水)和垂直传播。我们之前已经表明,由预测的免疫原性 NcMIC3、NcMIC1 和 NcROP2 表位组成的嵌合疫苗(recNcMIC3-1-R)可显著降低 BALB/c 小鼠的脑部感染。在这项研究中,首先对小鼠进行了疫苗接种,然后使其交配,怀孕的小鼠在怀孕的第 7-9 天用 2×10(6)刚地弓形虫速殖子进行攻毒。用速殖子粗蛋白提取物接种的小鼠仅观察到部分保护,而用 recNcMIC3-1-R 接种的小鼠在母鼠中未观察到针对垂直传播或脑部感染的保护。血清学和细胞因子分析显示,与主导的 IL-4 表达和高 IgG1 滴度相关的血清中细胞因子水平总体较低。因此,在怀孕的小鼠中观察到的 Th2 型免疫反应不能预防实验性新孢子虫病,这与在非怀孕小鼠模型中观察到的混合 Th1-/Th2 型免疫反应相反。这些结果表明,在怀孕期间发生的免疫调节不利于用 recNcMIC3-1-R 进行疫苗接种所产生的针对刚地弓形虫感染的保护。

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