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嗜水气单胞菌亚种鲑鱼的 III 型分泌系统抗原可预防虹鳟鱼的保护性免疫。

Antigens of the type-three secretion system of Aeromonas salmonicida subsp. salmonicida prevent protective immunity in rainbow trout.

机构信息

Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern, Switzerland.

出版信息

Vaccine. 2013 Oct 25;31(45):5256-61. doi: 10.1016/j.vaccine.2013.08.057. Epub 2013 Sep 5.

DOI:10.1016/j.vaccine.2013.08.057
PMID:24012573
Abstract

Aeromonas salmonicida subsp. salmonicida is the etiologic agent of furunculosis, a frequent and significant disease of fisheries worldwide. The disease is largely controlled by commercial oil adjuvanted vaccines containing bacterins. However, the mechanisms leading to a protective immune response remain poorly understood. The type-three secretion system (T3SS) plays a central role in virulence of A. salmonicida subsp. salmonicida and thus may have an influence on the immune response of the host. The aim of this study was to evaluate the role of the T3SS antigens in mounting a protective immune response against furunculosis. Rainbow trout were intraperitoneally vaccinated in two independent experiments with bacterins prepared from a wild-type A. salmonicida strain and an isogenic strain carrying a deletion in the T3SS (ΔascV). Fish were challenged with the wt strain eight weeks after vaccination. In both trials, the survival rate of trout vaccinated with the ΔascV strain was significantly higher (23-28%) in comparison to the group vaccinated with the wt strain. High-throughput proteomics analysis of whole bacteria showed the ascV deletion in the mutant strain resulted in lower expression of all the components of the T3SS, several of which have a potential immunosuppressive activity. In a third experiment, fish were vaccinated with recombinant AcrV (homologous to the protective antigen LcrV of Yersinia) or S-layer protein VapA (control). AcrV vaccinated fish were not protected against a challenge while fish vaccinated with VapA were partially protected. The presence of T3SS proteins in the vaccine preparations decreased the level of protection against A. salmonicida infection and that AcrV was not a protective antigen. These results challenge the hypothesis that mounting specific antibodies against T3SS proteins should bring better protection to fish and demonstrate that further investigations are needed to better understand the mechanisms underlying effective immune responses against A. salmonicida infection.

摘要

嗜水气单胞菌亚种鲑鱼是疖病的病原体,疖病是一种常见且严重的世界性渔业疾病。该疾病在很大程度上通过含有菌苗的商业油佐剂疫苗来控制。然而,导致保护性免疫反应的机制仍知之甚少。III 型分泌系统(T3SS)在嗜水气单胞菌亚种鲑鱼的毒力中起着核心作用,因此可能对宿主的免疫反应产生影响。本研究旨在评估 T3SS 抗原在引发疖病保护性免疫反应中的作用。在两项独立的实验中,虹鳟鱼通过腹腔内接种来自野生型嗜水气单胞菌菌株和携带 T3SS 缺失(ΔascV)的同基因菌株的菌苗来进行疫苗接种。接种后 8 周,用 wt 菌株对鱼进行攻毒。在这两项试验中,用 ΔascV 菌株接种的鱼的存活率明显高于用 wt 菌株接种的鱼(23-28%)。对全细菌进行高通量蛋白质组学分析表明,突变株中 ascV 的缺失导致 T3SS 的所有成分的表达水平降低,其中一些成分具有潜在的免疫抑制活性。在第三项实验中,鱼用重组 AcrV(与耶尔森氏菌的保护性抗原 LcrV 同源)或 S-层蛋白 VapA(对照)进行疫苗接种。AcrV 接种的鱼不能抵抗攻毒,而 VapA 接种的鱼则部分受到保护。疫苗制剂中 T3SS 蛋白的存在降低了对嗜水气单胞菌感染的保护水平,并且 AcrV 不是保护性抗原。这些结果挑战了针对 T3SS 蛋白产生特异性抗体应该为鱼类提供更好保护的假设,并表明需要进一步研究以更好地理解针对嗜水气单胞菌感染的有效免疫反应的机制。

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