The route to identification of the immunological correlates of protection in ruminants

有效的疫苗是预防传染病传播和扩散的最有效方法。这适用于人类和动物的疾病。然而，仍有许多疾病没有有效的疫苗。这可能是因为尚未对疫苗进行测试，因为已测试的疫苗没有保护作用，或者因为已测试的疫苗本身存在危害（益处与风险）。过去，疫苗是凭经验研制的。相比之下，开发安全有效疫苗的战略方法依赖于对免疫系统如何被激活和调节的理解，从而实现最佳的保护（效益）和最小的不良影响（风险）。对免疫系统的研究揭示了一种好的疫苗应该模仿的相关保护。由于每种感染的保护相关因素并不相同，针对不同疾病的疫苗需要刺激免疫系统的不同组成部分。与通常用作人类疾病模型的小实验动物（如小鼠）相比，在牛和羊等养殖反刍动物中识别免疫保护相关因素的能力相对较差。这主要是由于反刍动物免疫技术的相对缺乏。了解对感染的免疫反应最有效的方法是研究自然宿主。牛羊提供了一个很好的机会来做到这一点，它们是经济上重要疾病的宿主，但是缺乏对它们免疫系统的了解是战略疫苗开发的主要障碍。此外，与小鼠相比，这些动物可能是开发人类疾病解决方案的更好模型。在这个项目中，我们的目标是开发新的技术来研究牛和羊的免疫系统的激活和调节。这些技术将应用于在不同条件下活化的细胞的研究。这项工作将有助于确定对牛和羊的许多不同疾病提供保护的免疫学相关性，并将为提供新疫苗以最大限度地发挥其作用的最佳方式提供信息。最终，这将导致管理和控制养殖反刍动物传染病的更具战略性的方法。这将通过改善动物福利、动物生产和粮食安全，使农业部门和公众受益。此外，这项工作将与一个工业伙伴共同完成，确保项目中开发的技术和试剂将广泛提供给研究界。

Effective vaccines are the most efficient way of preventing the transmission and spread of infectious diseases. This applies to diseases of both humans and animals. However there are still many diseases for which no effective vaccines exist. This may be because no vaccines have yet been tested, because vaccines that have been tested do not protect, or because vaccines that have been tested present a hazard in themselves (benefit versus risk). In the past, vaccines were developed empirically. In contrast, strategic approaches to the development of safe and effective vaccines relies on an understanding of how the immune system is activated and regulated so that optimum protection is achieved (benefit) with minimum adverse effects (risk). Investigation of the immune system reveals the correlates of protection that should be mimicked by a good vaccine. Since the correlates of protection are not the same for every infection, vaccines against different diseases need to stimulate different components of the immune system. The capability to identify immunological correlates of protection in farmed ruminants such as cattle and sheep is relatively poor compared to small laboratory animals such as mice that are commonly used as models of human disease. This is largely due to a relative paucity of immunological techniques in ruminants. The most effective way of understanding immune responses to infection is to study the natural host. Cattle and sheep offer an excellent opportunity to do this, and are hosts for economically important diseases, but the lack of knowledge of their immune systems is a major block to strategic vaccine development. Furthermore, these animals may represent better models for developing solutions to human diseases than mice. In this project we aim to develop new techniques to investigate the activation and regulation of the immune systems of cattle and sheep. These techniques will be applied to studies on cells activated under different conditions. This work will facilitate the identification of immunological correlates of protection to many different diseases of cattle and sheep and will also inform on the best ways to deliver new vaccines to maximise their effects. Ultimately this will lead to more strategic approaches to the management and control of infectious diseases of farmed ruminants. This will benefit the agricultural sector and the general public through improved animal welfare, animal production and food security. Furthermore, the work will be done in conjunction with an Industrial Partner, ensuring that the techniques and reagents developed in the project will be made widely available to the research community.