Development of improved vaccines effective against emerging strains of the fish pathogen Yersinia ruckeri

开发有效对抗鱼类病原体鲁氏耶尔森氏菌新菌株的改良疫苗

• 批准号: BB/I01554X/1
• 金额: $ 11.71万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Training Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI01554X%2F1
• 关键词: Development; improved; vaccines; effective; against

Despite advances in vaccine development and chemotherapy, bacterial pathogens remain a significant constraint to aquaculture production, as well as a potential threat to wild stocks. In addition to so-called 'new' bacterial pathogens, the threat often comes from established pathogens evolving to circumvent developed control strategies. An example of such an evolving pathogen is the Gram-negative bacterium Yersinia ruckeri which causes economically-important infections of Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). Y. ruckeri has been identified as the aetiological agent of enteric redmouth disease (ERM) of farmed rainbow trout in England and Wales for more than thirty years. The organism also causes significant outbreaks of disease in farmed Atlantic salmon but very little is known about the epidemiology of Y. ruckeri in this species. Until recently, Y. ruckeri posed a reduced risk to farmed trout and salmon due largely to the extensive use of vaccination. However, increasing worldwide reports of vaccine breakdown in the field are believed to be associated with the emergence of new pathogenic strains of Y. ruckeri. Traditionally, the majority of ERM infections in rainbow trout in the USA and Europe have been caused by a subgroup (biotype) of closely-related serotype O1 Y. ruckeri strains represented by the so-called Hagerman strain. However, a new and distinct serotype O1 biotype has emerged in recent years that was first identified in the UK but which is now increasingly affecting rainbow trout production across Europe and the USA. Isolates recovered from infected Atlantic salmon appear to be more diverse and represent a wider range of O-serotypes (O1, O2 and O5). Preliminary evidence suggests that salmon-pathogenic serotypes are significantly less pathogenic to rainbow trout than they are to Atlantic salmon. The outer membrane (OM) of Gram-negative bacteria is at the interface between pathogen and host and outer membrane proteins (OMPs) play key roles in host-pathogen interactions such as adherence and colonization, nutrient uptake (specifically iron acquisition), evasion of the host immune response and secretion of virulence factors. Because many of these OMPs are under strong selection pressures (e.g. from the host immune system) they can exhibit varying degrees of diversity within a single bacterial species. This diversity is likely to confer upon strains different virulence attributes and host tropisms. In addition, many OMPs are surface-exposed and immunogenic and are therefore likely to serve as protective antigens. Despite the importance of Y. ruckeri as a pathogen of farmed salmonids, very little is known about the diversity of its OMPs in different strains or their roles in the disease process. Furthermore, very little is known about the host immune response to Y. ruckeri in salmon and trout or about the bacterial factors responsible for providing protection against infection. The aims of this project are as follows: 1. To carry out an epidemiological survey of the prevalence of Y. ruckeri in Scottish salmon and assess the effectiveness of transmission of the organism in seawater. 2. To characterize the OM proteomes of key selected isolates of Y. ruckeri recovered from salmon and trout under different growth conditions and identify cross-protective antigens (and potential vaccine candidates) by immunoproteomics. 3. To compare the virulence of selected isolates for Atlantic salmon and trout. 4. To compare the kinetics of the immune response to selected isolates of Y. ruckeri in Atlantic salmon and trout. 5. To study serotype specificity of immunity and the protection afforded by vaccines prepared from different isolates of Y. ruckeri in Atlantic salmon and trout.

尽管疫苗开发和化疗取得了进展，细菌病原体仍然是水产养殖生产的重大限制，并对野生种群构成潜在威胁。除了所谓的“新”细菌病原体外，威胁还常常来自为规避已制定的控制策略而进化的现有病原体。这种不断进化的病原体的一个例子是革兰氏阴性细菌鲁氏耶尔森氏菌，它会引起大西洋鲑鱼（Salmo salar）和虹鳟鱼（Oncorhynchus mykiss）的经济上重要的感染。三十多年来，鲁氏耶氏杆菌已被确定为英格兰和威尔士养殖虹鳟鱼肠道红嘴病 (ERM) 的病原体。该生物体还会导致养殖大西洋鲑鱼严重爆发疾病，但人们对鲁氏耶尔森氏菌在该物种中的流行病学知之甚少。直到最近，鲁氏耶氏杆菌对养殖鳟鱼和鲑鱼的风险降低，这主要是由于疫苗的广泛使用。然而，世界范围内越来越多的疫苗在现场失效的报告被认为与鲁氏耶尔森氏菌新致病菌株的出现有关。传统上，美国和欧洲虹鳟鱼的大多数 ERM 感染是由密切相关的 O1 Y. ruckeri 血清型亚组（生物型）引起的，以所谓的 Hagerman 菌株为代表。然而，近年来出现了一种新的独特血清型 O1 生物型，该生物型首先在英国发现，但现在越来越多地影响欧洲和美国的虹鳟鱼生产。从受感染的大西洋鲑鱼中回收的分离株似乎更加多样化，代表了更广泛的 O 血清型（O1、O2 和 O5）。初步证据表明，鲑鱼致病血清型对虹鳟鱼的致病性明显低于对大西洋鲑鱼的致病性。革兰氏阴性菌的外膜 (OM) 位于病原体和宿主之间的界面，外膜蛋白 (OMP) 在宿主与病原体的相互作用中发挥着关键作用，例如粘附和定植、营养吸收（特别是铁的获取）、逃避宿主免疫反应和毒力因子的分泌。由于许多 OMP 面临强大的选择压力（例如来自宿主免疫系统的选择压力），因此它们可以在单一细菌物种内表现出不同程度的多样性。这种多样性可能赋予菌株不同的毒力属性和宿主向性。此外，许多 OMP 是表面暴露的且具有免疫原性，因此可能充当保护性抗原。尽管鲁氏耶尔森氏菌作为养殖鲑鱼的病原体很重要，但人们对其 OMP 在不同菌株中的多样性或其在疾病过程中的作用知之甚少。此外，人们对鲑鱼和鳟鱼中对鲁氏耶氏菌的宿主免疫反应或负责提供抗感染保护的细菌因素知之甚少。该项目的目标如下： 1. 对苏格兰鲑鱼中鲁氏耶尔森氏菌的流行情况进行流行病学调查，并评估该生物体在海水中传播的有效性。 2. 表征在不同生长条件下从鲑鱼和鳟鱼中回收的 Y. ruckeri 关键选定分离株的 OM 蛋白质组，并通过免疫蛋白质组学鉴定交叉保护性抗原（和潜在的候选疫苗）。 3. 比较所选分离株对大西洋鲑鱼和鳟鱼的毒力。 4. 比较大西洋鲑鱼和鳟鱼中选定的鲁氏耶氏菌分离株的免疫反应动力学。 5. 研究大西洋鲑鱼和鳟鱼的免疫血清型特异性以及由鲁氏耶尔森氏菌不同分离株制备的疫苗所提供的保护。