Identifying epitopes that induce antibody mediated protection against foot-and-mouth disease using reverse genetics

口蹄疫病毒（Foot-and-mouth disease virus，FMDV）是一种危害偶蹄类家畜和野生动物的高传染性疾病。口蹄疫是限制活动物和动物产品国际贸易的唯一最重要因素。控制该病的方法通常是限制动物活动和屠宰受感染和接触过的动物，这是非常昂贵和不受公众欢迎的。2001年在英国最近爆发的口蹄疫大大提高了公众对这种疾病的认识，现在人们对一项战略的兴趣越来越大，该战略包括一项"接种疫苗以维持生命的政策"，以补充消灭口蹄疫作为控制口蹄疫爆发的一种手段。接种疫苗的动物产生抗体，这些抗体被认为在提供针对FMD的保护方面是重要的。然而，目前还不清楚这些抗体如何提供保护，也不清楚病毒的哪些部分对于最佳保护是最重要的。口蹄疫病毒有许多变种，需要多种疫苗株来预防所有这些变种。目前选择最合适的疫苗的方法不是很标准化或可靠的，因为依赖于在动物中产生的抗血清，这些动物对疫苗接种没有一致的反应。本计划将利用基因工程技术，构建一系列密切相关的口蹄疫病毒，其中病毒外壳表面的个别特征将被轻微改变，以影响抗体识别。通过观察这些病毒中的每一种被免疫动物的抗体识别的程度，以及每一种病毒能够诱导FMD保护性免疫应答的程度，我们将建立一个关于每一种特征对抗体介导的保护作用的贡献的图片。更好地了解需要哪些病毒结构来诱导保护性免疫反应，将使我们能够准确和更快速地预测哪些疫苗具有必要的配置来提供对FMDV新毒株的保护。这将是巨大的好处时，面临的决定是否和在哪里应用紧急疫苗接种面对一个新的口蹄疫入侵，因为任何疫苗接种计划的有效性是在很大程度上取决于其实施的速度。这些知识也将对开发广谱口蹄疫疫苗的努力具有根本价值，这将大大改善全球口蹄疫控制和根除的前景。

Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious and economically devastating disease of cloven hoofed domestic and wild animals. FMD is the single most important constraint to international trade in live animals and animal products. The disease is generally controlled by restriction of animal movement and slaughter of infected and in-contact animals which is very costly and unpopular with the public. The recent outbreaks in the United Kingdom in 2001, have significantly increased public awareness of this disease and now there is heightened interest in a strategy that encompasses a 'vaccinate to-live-policy' to complement stamping out as a means of controlling FMD outbreaks. Vaccinated animals produce antibodies which are believed to be important in providing protection against FMD. However, it is not well understood how such antibodies provide protection nor which parts of the virus are most important to be recognised for protection to be optimal. There are many variants of the FMD virus and multiple vaccine strains are needed to protect against all of these. Current methods to select the most appropriate vaccine are not well standardised or reliable because of dependence on antisera raised in animals that do not react to vaccination in a consistent manner. This project will use genetic engineering to construct a series of closely related FMD viruses in which individual features on the surface of the virus shell will have been slightly altered so as to affect antibody recognition. By looking at how well each of these viruses is recognised by antibodies from immune animals and by seeing how well each virus is able to induce a FMD protective immune response, we shall build up a picture of the contribution of each feature to antibody mediated protection. A better understanding of which viral structures are needed to induce a protective immune response will enable us to make accurate and much more rapid predictions of which vaccines have the necessary configurations to offer protection against a new strain of FMDV. This will be of enormous benefit when faced with the decision of whether and where to apply emergency vaccination in the face of a new FMD incursion, since the effectiveness of any vaccination programme is heavily dependent on the speed of its implementation. This knowledge will also be of fundamental value in efforts to develop broader spectrum FMD vaccines that would dramatically improve the prospects for global FMD control and eradication.