Prophylactic measures in rainbow trout aquaculture: Further development of a DNA vaccine for proliferative kidney disease.

虹鳟鱼水产养殖的预防措施：进一步开发增殖性肾病 DNA 疫苗。

• 批准号: BB/K009125/1
• 负责人: Chris Secombes
• 金额: $ 29.37万
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FK009125%2F1
• 关键词: Prophylactic; measures; rainbow; trout; aquaculture

Our proposed work will study an important disease, affecting the rainbow trout aquaculture industry in the UK and central Europe, called proliferative kidney disease (PKD). The disease is caused by a microscopic parasite distantly related to jellyfish, which causes a severe immune response in fish characterized by chronic kidney pathology. Recent studies discovered colonial freshwater invertebrates, called bryozoans, can harbour the parasite stage infective to fish with a clear link between increasing water temperatures and increased parasite proliferation in bryozoans. This causes an increase in the release of infective parasite spores suggesting that the disease is likely to become more problematic in farmed and wild salmonid stocks as water temperature trends increase due to climate change. This has already been clearly seen in wild brown trout populations in Switzerland and wild Atlantic salmon stocks in Norway and in the increasing prevalence of PKD in recent years in trout farms in Southern England. There are no current treatments or means of controlling the disease. Importantly, however, there is a great deal of potential to develop a treatment since it is known that fish surviving parasite infection are resistant to the disease upon parasite re-exposure. Thus, the vaccination of fish is expected to be one way to control the disease. Vaccination will be based on finding molecules secreted from or found on the surface of the parasite in direct contact with the fish immune system. Such molecules can prime the immune system to react quickly when exposed to the parasite preventing or reducing chronic infection and associated fish mortalities. In recent studies we used parasite material isolated from bryozoans in molecular biology techniques to create a "gene library". Gene pools created from this library enabled us to examine the ability of thousands of parasite molecules to prime the fish immune system and protect against disease pathology or to slow the onset of advanced clinical disease. Different gene pools were administered to fish by DNA vaccination in line with recent advances in vaccine technology, representing a more cost effective approach to discover suitable vaccine candidates than using conventional protein-based methods. Fish were vaccinated at a commercial rainbow trout farm that suffers from this disease every year. Results were assessed in terms of the extent of disease pathology and parasite abundance in kidney tissue. After two sequential rounds of subdivision and retesting of the most protective gene pool, we were able to identify a single batch of 182 parasite molecules slowing the onset of kidney pathology. The commercial exploitability of such vaccine studies is highly dependent on the identification and full characterization of single parasite protective molecules. So in this proposal we aim to take the next steps towards PKD vaccine development by subdividing and retesting this gene batch in order to identify and characterize the parasite molecules conveying disease protection. The majority of parasite molecules will be found in both infected hosts, with a minority being host-specific. Parasite molecules capable of protecting fish against the disease must either be found in both hosts or are fish-specific. From our previous studies, we have created a parasite gene library from infected fish. We, therefore, further propose to use a high throughput molecular biology technique to determine which parasite molecules are predominantly or solely found in the fish host relative to the bryozoan host and to test those "fish-specific" molecules predicted to be secreted from or found on the surface of parasites within the infected fish kidney. Overall, we will take a systematic approach to further vaccine development for PKD, exploiting our past success in uncovering a single protective parasite gene pool, our existing expertise in molecular biology, PKD biology and fish vaccination.

我们提出的工作将研究一种重要的疾病，影响英国和中欧的彩虹鳟鱼水产养殖业，称为增殖性肾脏疾病（PKD）。该疾病是由与水母相关的微观寄生虫引起的，水母会导致以慢性肾脏病理学为特征的鱼类的严重免疫反应。最近的研究发现，殖民地淡水无脊椎动物，称为bryozoans，可以在水温升高和增加的铜矿寄生虫增殖之间具有明显联系的寄生虫感染性。这会导致感染性寄生虫孢子的释放增加，这表明随着气候变化导致的水温趋势的增加，这种疾病在养殖和野生鲑鱼库存中可能会变得更加问题。在瑞士的野生棕褐色种群和挪威的野生大西洋鲑鱼库存以及PKD近年来在英格兰南部的鳟鱼农场越来越普遍的野生大西洋鲑鱼库存中，已经清楚地看到了这一点。目前没有控制该疾病的治疗方法。然而，重要的是，由于众所周知，在寄生虫重暴露时，众所周知，生存的寄生虫感染对这种疾病具有抗性，因此有很大的潜力进行治疗。因此，预计鱼类的疫苗接种是控制疾病的一种方法。疫苗接种将基于发现从寄生虫表面分泌或发现的分子，直接与鱼类免疫系统接触。这种分子可以在暴露于寄生虫时迅速反应，以防止或减少慢性感染和相关的鱼类死亡。在最近的研究中，我们使用了从苔藓植物中分离出的寄生虫材料，以分子生物学技术创建“基因文库”。从该图书馆创建的基因池使我们能够检查成千上万的寄生虫分子为鱼类免疫系统灌注并防止疾病病理学或减慢晚期临床疾病的发作的能力。与使用基于蛋白质的常规方法相比，通过DNA疫苗接种，通过DNA疫苗接种来施用不同的基因库，这是发现合适的疫苗候选物的一种更具成本效益的方法。鱼在每年患有这种疾病的商业彩虹鳟鱼农场接种疫苗。根据肾脏组织中疾病病理和寄生虫丰度的程度评估结果。经过两轮的细分和最具保护基因库的重新测试后，我们能够鉴定出一批182个寄生虫分子，从而减慢了肾脏病理学的发作。这种疫苗研究的商业可剥削性高度取决于单个寄生虫保护分子的鉴定和全面表征。因此，在这项建议中，我们旨在通过对PKD疫苗开发的下一步迈进，通过细分和重新测试该基因批次，以识别和表征传达疾病保护的寄生虫分子。大多数寄生虫分子都会在两个受感染的宿主中发现，少数是宿主特异性的。能够保护鱼免受这种疾病的寄生虫分子必须在两种宿主中找到或特定于鱼类。从我们以前的研究中，我们创建了一个来自感染鱼类的寄生虫基因文库。因此，我们进一步建议使用高吞吐分子生物学技术来确定哪些寄生虫分子主要或仅在鱼宿主中相对于Bryozoan宿主发现，并测试被预测的“鱼类特异性”分子，预计将从感染的鱼肾脏中属于或在感染的鱼卵中寄生的表面上分泌或发现。总体而言，我们将采用一种系统的方法来进一步开发PKD的疫苗开发，从而利用了我们过去在揭示单个保护性寄生虫基因池的成功，这是我们现有的分子生物学，PKD生物学和鱼类疫苗接种的现有专业知识。

项目成果

First in-depth analysis of the novel Th2-type cytokines in salmonid fish reveals distinct patterns of expression and modulation but overlapping bioactivities.

• DOI: 10.18632/oncotarget.7295
• 发表时间: 2016-03-08
• 期刊: Oncotarget
• 作者: Wang T;Johansson P;Abós B;Holt A;Tafalla C;Jiang Y;Wang A;Xu Q;Qi Z;Huang W;Costa MM;Diaz-Rosales P;Holland JW;Secombes CJ
• 通讯作者: Secombes CJ

Dysregulation of B Cell Activity During Proliferative Kidney Disease in Rainbow Trout.

• DOI: 10.3389/fimmu.2018.01203
• 发表时间: 2018
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Abos B;Estensoro I;Perdiguero P;Faber M;Hu Y;Díaz Rosales P;Granja AG;Secombes CJ;Holland JW;Tafalla C
• 通讯作者: Tafalla C

Differential expression, modulation and bioactivity of distinct fish IL-12 isoforms: implication towards the evolution of Th1-like immune responses.

不同鱼类 IL-12 亚型的差异表达、调节和生物活性：对 Th1 样免疫反应进化的影响。

• DOI: 10.1002/eji.201344273
• 发表时间: 2014
• 期刊: European journal of immunology
• 影响因子: 5.4
• 作者: Wang T

Identification and expression analysis of an atypical chemokine receptor-2 (ACKR2)/CC chemokine binding protein-2 (CCBP2) in rainbow trout (Oncorhynchus mykiss).

• DOI: 10.1016/j.fsi.2015.02.038
• 发表时间: 2015-06
• 期刊: Fish & shellfish immunology
• 影响因子: 4.7
• 作者: Z. Qi;Yousheng Jiang;J. Holland;P. Nie;C. Secombes;Tiehui Wang

Sequence and expression analysis of rainbow trout CXCR2, CXCR3a and CXCR3b aids interpretation of lineage-specific conversion, loss and expansion of these receptors during vertebrate evolution.

虹鳟鱼 CXCR2、CXCR3a 和 CXCR3b 的序列和表达分析有助于解释脊椎动物进化过程中这些受体的谱系特异性转化、丢失和扩展

• DOI: 10.1016/j.dci.2014.03.002
• 发表时间: 2014-08
• 期刊: DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
• 影响因子: 2.9
• 作者: Xu, Qiaoqing;Li, Ronggai;Monte, Milena M.;Jiang, Yousheng;Nie, Pin;Holland, Jason W.;Secornbes, Chris J.;Wang, Tiehui
• 通讯作者: Wang, Tiehui