Haldorson G J, Mathison B A, Wenberg K, Conrad P A, Dubey J P, Trees A J, Yamane I, Baszler T V
Department of Veterinary Microbiology and Pathology, Washington State University, Bustad Hall, Pullman, WA 99164-7040, USA.
Int J Parasitol. 2005 Nov;35(13):1407-15. doi: 10.1016/j.ijpara.2005.05.013. Epub 2005 Jul 18.
NcSRS2, a tachyzoite surface protein of Neospora caninum, is an immunodominant protein with respect to induction of antibody production and has a role in attachment and invasion of host cells. Native NcSRS2 was isolated from whole tachyzoite lysate antigen by affinity chromatography using NcSRS2 specific monoclonal antibody and used to immunize BALB/c mice in a congenital transmission study. NcSRS2 was a highly conserved protein as indicated by comparison of deduced amino acid sequence obtained from NcSRS2 gene sequences of 10 geographically distinct N. caninum isolates. Mice immunized with purified native NcSRS2 produced antigen-specific antibody, primarily of IgG 1 subtype. Following challenge during gestation with 10(7) tachyzoites, immunized mice had a statistically significant decreased frequency of congenital transmission compared to non-immunized mice (P<or=0.05) or mice inoculated with adjuvant alone (P<or=0.01). Decreased congenital transmission among immunized mice correlated with a predominately Th2 immune response compared to non-immunized mice as indicated by an increased ratio of interleukin 4 (IL-4) to interferon gamma (IFN-gamma) secretion from antigen-stimulated splenocytes. The results provide a rationale for NcSRS2 as a candidate subunit vaccine antigen for reduction of N. caninum congenital transmission. Furthermore, the studies suggest that a Th2 immune response, if directed against an appropriate antigen, may induce protection against N. caninum congenital infection in mice.
NcSRS2是犬新孢子虫速殖子表面蛋白,是诱导抗体产生的免疫显性蛋白,在宿主细胞的附着和入侵中起作用。天然NcSRS2通过使用NcSRS2特异性单克隆抗体的亲和层析从全速殖子裂解物抗原中分离出来,并用于先天性传播研究中免疫BALB/c小鼠。从10个地理上不同的犬新孢子虫分离株的NcSRS2基因序列推导的氨基酸序列比较表明,NcSRS2是一种高度保守的蛋白。用纯化的天然NcSRS2免疫的小鼠产生了抗原特异性抗体,主要是IgG 1亚型。在妊娠期间用10(7)个速殖子攻击后,与未免疫小鼠(P≤0.05)或仅接种佐剂的小鼠(P≤0.01)相比,免疫小鼠的先天性传播频率有统计学意义的降低。与未免疫小鼠相比,免疫小鼠先天性传播的减少与主要的Th2免疫反应相关,这表现为抗原刺激的脾细胞中白细胞介素4(IL-4)与干扰素γ(IFN-γ)分泌的比例增加。这些结果为NcSRS2作为减少犬新孢子虫先天性传播的候选亚单位疫苗抗原提供了理论依据。此外,研究表明,如果针对合适的抗原,Th2免疫反应可能诱导小鼠对犬新孢子虫先天性感染的保护作用。