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

口蹄疫病毒(FMDV)是一种高度传染性和经济破坏性的偶蹄家畜和野生动物疾病的病原体。口蹄疫是活体动物和动物产品国际贸易的一个最重要的制约因素。这种疾病一般是通过限制动物活动和宰杀受感染和接触的动物来控制的，这是非常昂贵的，而且不受公众欢迎。2001年英国最近的疫情极大地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增强，该战略包括一项“疫苗接种到活着的政策”，以补充作为控制口蹄疫爆发的一种手段的杜绝。接种疫苗的动物会产生抗体，这种抗体被认为对预防口蹄疫很重要。然而，目前还不清楚这些抗体是如何提供保护的，也不知道病毒的哪些部分是最重要的，才能获得最佳的保护。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。目前选择最合适疫苗的方法不是很标准化或可靠，因为依赖于对疫苗接种没有一致反应的动物体内产生的抗血清。这个项目将利用基因工程来构建一系列密切相关的口蹄疫病毒，在这些病毒壳表面的个别特征将被轻微改变，以影响抗体识别。通过观察来自免疫动物的抗体对每种病毒的识别情况，以及每种病毒诱导口蹄疫保护性免疫反应的情况，我们将建立一幅每种特征对抗体介导的保护的贡献图。更好地了解需要哪些病毒结构来诱导保护性免疫反应，将使我们能够更准确、更快速地预测哪些疫苗具有针对新的口蹄疫病毒株提供保护的必要配置。在面对新的口蹄疫入侵时决定是否以及在哪里应用紧急疫苗接种时，这将是巨大的好处，因为任何疫苗接种方案的有效性在很大程度上取决于其实施的速度。这些知识在努力开发更广泛的口蹄疫疫苗方面也将具有基本价值，这些疫苗将极大地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.