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犊牛肌肉注射疫苗预防肠道寄生虫牛古柏线虫后的保护性免疫反应分析。

Analysis of the protective immune response following intramuscular vaccination of calves against the intestinal parasite Cooperia oncophora.

作者信息

Van Meulder F, Ratman D, Van Coppernolle S, Borloo J, Li R W, Chiers K, Van den Broeck W, De Bosscher K, Claerebout E, Geldhof P

机构信息

Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

Receptor Research Laboratories, Nuclear Receptor Lab, VIB-Department of Medical Protein Research, VIB, Ghent University, Ghent, Belgium.

出版信息

Int J Parasitol. 2015 Aug;45(9-10):637-46. doi: 10.1016/j.ijpara.2015.03.007. Epub 2015 May 1.

DOI:10.1016/j.ijpara.2015.03.007
PMID:25937360
Abstract

Recently we reported the successful vaccination of calves against Cooperia oncophora with a double domain activation-associated secreted protein, purified from the excretory-secretory material of adult stage parasites. In an attempt to elucidate the immune mechanisms involved in protection, the humoral and cell-mediated immune responses following vaccination and infection were compared with non-vaccinated control animals. Antigen-specific IgG1, IgG2 and IgA levels were significantly increased in sera of vaccinated animals post vaccination, whereas no effect was observed for IgM. Antigen-specific intestinal IgG1 levels were significantly increased in the vaccinated animals, whereas no differences were observed for antigen-specific IgA, IgM and IgG2 levels. Upon re-stimulation in vitro with the vaccine antigen, a significant proliferation of both αβ- and γδ-T cells, and B cells, collected from mesenteric lymph nodes, was only observed in vaccinated animals. RNA-seq analysis of intestinal tissue yielded a list of 67 genes that were differentially expressed in vaccinated animals following challenge infection, amongst which were several cell adhesion molecules, lectins and glycosyl transferases. A correlation analysis between all immunological and parasitological parameters indicated that intestinal anti-double domain activation-associated secreted protein IgG1 levels correlated negatively with cumulative faecal egg counts and positively with the proportion of L4s and L5s. The proportion of immature stages was also positively correlated with the proliferation of αβ T cells. Worm length was negatively correlated with the transcript levels of several lectins and cell adhesion molecules. Overall, the results indicate that intramuscular administration of the vaccine resulted in an immune memory response particularly characterised by increased antigen-specific IgG1 levels in the intestinal mucosa.

摘要

最近,我们报道了用从成年期寄生虫的排泄-分泌物质中纯化的双结构域激活相关分泌蛋白成功地对犊牛进行抗柯氏圆线虫疫苗接种。为了阐明参与保护的免疫机制,将接种疫苗和感染后的体液免疫和细胞介导免疫反应与未接种疫苗的对照动物进行了比较。接种疫苗的动物血清中抗原特异性IgG1、IgG2和IgA水平在接种后显著升高,而IgM未观察到影响。接种疫苗的动物肠道中抗原特异性IgG1水平显著升高,而抗原特异性IgA、IgM和IgG2水平未观察到差异。在用疫苗抗原进行体外再刺激时,仅在接种疫苗的动物中观察到从肠系膜淋巴结收集的αβ-T细胞、γδ-T细胞和B细胞显著增殖。对肠道组织的RNA测序分析产生了一份67个基因的列表,这些基因在攻击感染后的接种疫苗动物中差异表达,其中包括几种细胞粘附分子、凝集素和糖基转移酶。所有免疫学和寄生虫学参数之间的相关性分析表明,肠道抗双结构域激活相关分泌蛋白IgG1水平与粪便虫卵累计计数呈负相关,与L4和L5的比例呈正相关。未成熟阶段的比例也与αβ T细胞的增殖呈正相关。虫体长度与几种凝集素和细胞粘附分子的转录水平呈负相关。总体而言,结果表明肌肉注射疫苗导致了免疫记忆反应,其特征尤其表现为肠道黏膜中抗原特异性IgG1水平升高。

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