Immunity safety and protection of an Adenovirus-Prime:MVA-Boost vaccine against Mycobacterium avium subspecies paratuberculosis infection in calves

腺病毒-Prime:MVA-Boost 疫苗针对犊牛鸟分枝杆菌亚种副结核感染的免疫安全性和保护作用

• 批准号: BB/H010718/1
• 负责人: Jayne Hope
• 金额: $ 30.06万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research 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%2FH010718%2F1
• 关键词: Immunity; safety; protection; Adenovirus; Prime

Mycobacterium avium subspecies paratuberculosis (MAP) is the bacterium that causes a chronic inflammation of the gut known as Johne's disease (JD) in many animals. JD is of significant economic importance to the management of cattle, sheep and goats due to loss in milk production and the need for premature culling when the disease becomes advanced; the cost has been estimated to be $1.5billion pa. in the USA and £13million pa. in the UK. Current measures to control the spread of JD have been shown to be inadequate and at present more than half of cattle herds in the UK are infected and nearly all herds in some other developed countries, including the USA. MAP is excreted in very large amounts in later stages of infection but can also be excreted even when current vaccines are used. This has led to the spread of MAP into wildlife reservoirs and contamination of environmental reservoirs such as rivers and lakes. MAP is excreted by infected dairy cattle in their milk and is present in supermarket milk as it survives pasteurization. There is an increasingly convincing link between MAP infection and Crohn's disease in humans, MAP has been detected in up to half of normal human intestinal samples and nearly all of Crohn's Disease samples. Currently, commercially available whole cell vaccines do not provide complete protection against JD. They may relieve clinical symptoms but do not significantly reduce the number of animals that are infected or stop excretion of MAP into milk and faeces. By allowing the induction of sub-clinical infection, these vaccines may hide the problem of MAP infection and consequently be counterproductive. Therefore, there is an urgent need to develop a better vaccine to treat this disease and to understand the way that MAP affects the animal's immune system to cause JD. This project will study a new type of vaccine that has been shown to work in mice. It uses two viruses that will not grow in animals or the environment, to deliver a cocktail of MAP antigens called HAV. Although vaccination trials in mice do not always transfer successfully to other animal species, results from preliminary experiments have shown that the prime-boost vaccination method we are proposing to use has been beneficial in conferring a degree of protection against other mycobacterial infections. We will look at the ability of the HAV vaccine to prevent an experimental infection of calves with MAP and measure in detail the cattle's immune system with the aim of understanding how this new type of vaccine might be working. This work will improve our knowledge of mycobacterial disease processes and could therefore also benefit other related research such as vaccines for tuberculosis for example. If the study does show that the new vaccine may be protective it could be a first step in improving the control of this increasingly spreading disease.

鸟分枝杆菌副结核亚种 (MAP) 是一种在许多动物中引起肠道慢性炎症（称为约翰氏病 (JD)）的细菌。 JD 对牛、绵羊和山羊的管理具有重要的经济意义，因为当疾病进展时，牛奶产量会下降，并且需要过早扑杀；每年的成本估计为 15 亿美元。在美国，每年 1300 万英镑。在英国。目前控制 JD 传播的措施已被证明是不够的，目前英国一半以上的牛群都受到感染，而包括美国在内的其他一些发达国家的几乎所有牛群都受到感染。 MAP 在感染后期会大量排出，但即使使用当前的疫苗也可能被排出。这导致MAP扩散到野生动物水库并污染河流和湖泊等环境水库。 MAP 是由受感染的奶牛在牛奶中排出的，并且在经过巴氏灭菌后仍存在于超市牛奶中。 MAP 感染与人类克罗恩病之间的联系越来越令人信服，在多达一半的正常人类肠道样本和几乎所有克罗恩病样本中都检测到了 MAP。目前，市售的全细胞疫苗不能提供针对 JD 的完全保护。它们可以缓解临床症状，但不会显着减少受感染的动物数量或阻止 MAP 排泄到牛奶和粪便中。通过诱导亚临床感染，这些疫苗可能会掩盖 MAP 感染的问题，从而产生反作用。因此，迫切需要开发更好的疫苗来治疗这种疾病，并了解 MAP 影响动物免疫系统导致 JD 的方式。该项目将研究一种已被证明对小鼠有效的新型疫苗。它使用两种不会在动物或环境中生长的病毒来提供称为 HAV 的 MAP 抗原混合物。尽管小鼠疫苗接种试验并不总能成功转移到其他动物物种，但初步实验结果表明，我们建议使用的初免-加强疫苗接种方法对于赋予针对其他分枝杆菌感染的一定程度的保护作用是有益的。我们将研究 HAV 疫苗预防小牛实验性感染 MAP 的能力，并详细测量牛的免疫系统，目的是了解这种新型疫苗如何发挥作用。这项工作将提高我们对分枝杆菌疾病过程的了解，因此也可能有益于其他相关研究，例如结核病疫苗。如果这项研究确实表明新疫苗可能具有保护作用，那么这可能是改善对这种日益蔓延的疾病的控制的第一步。

项目成果

Evaluation of immune responses to Mycobacterium avium paratuberculosis challenge in cattle

牛对副结核分枝杆菌攻击的免疫反应评估

• 发表时间: 2012
• 作者: Vrettou, C

Characterisation of a novel myeloid cell population in cattle blood and its potential involvement with Johne's Disease

牛血液中新型骨髓细胞群的特征及其与约内氏病的潜在关系

• 发表时间: 2013
• 期刊: 10th International Veterinary Immunology Symposium
• 作者: Corripio-Miyar, Y

Immunity, safety and protection of an Adenovirus 5 prime--Modified Vaccinia virus Ankara boost subunit vaccine against Mycobacterium avium subspecies paratuberculosis infection in calves.

• DOI: 10.1186/s13567-014-0112-9
• 发表时间: 2014-10-29
• 期刊: Veterinary research
• 影响因子: 4.4
• 作者: Bull TJ;Vrettou C;Linedale R;McGuinnes C;Strain S;McNair J;Gilbert SC;Hope JC
• 通讯作者: Hope JC

Evaluation of immune responses to Mycobacterium avium paratuberculosis in cattle

牛副结核分枝杆菌免疫反应的评估

• 发表时间: 2013
• 作者: Vrettou, C