VACCINE - Development of novel picornavirus virus-like particle vaccines

医学研究理事会的战略是促进全世界国际卫生研究的进展。疫苗接种对人类和动物健康产生了巨大影响，因此是最重要和最有效的医疗干预措施之一。然而，仍然有许多疾病的例子，我们没有有效的疫苗。此外，我们目前的疫苗生产大多涉及致病因子（如病毒）的生产，这些致病因子随后在生产过程中被灭活。用最简单的话来说，病毒可以被认为是保护内部病毒遗传物质的蛋白质容器。这个容器是惰性的--它是里面的病毒遗传物质，是引起疾病的原因。然而，容器（衣壳）在通过接种疫苗产生免疫力的过程中至关重要。在这里，身体的免疫系统识别衣壳蛋白并产生抗体，然后保护身体免受疾病的侵害。因此，仅产生衣壳作为病毒样颗粒（VLP）应该引起保护性免疫应答，但完全安全。此外，这种生产可以在低封闭度下进行，既容易又便宜，从而使发展中国家更容易获得这种病毒样颗粒疫苗。然而，存在需要克服的问题，因为许多VLP不稳定。我们有大量关于脊髓灰质炎病毒VLP生产的原理证明数据，并且已经产生了稳定的VLP，其提供比当前脊髓灰质炎疫苗更好的保护（在动物模型中）。我们现在希望将我们的策略应用于其他病毒，重点是手足口病的病原体。这是一种日益受到关注的疾病，特别是在东南亚地区爆发，与住院和死亡有关。根据世界卫生组织的数据，截至2012年7月底，中国有1，520，274人受到影响，据报有431人死亡，目前欧洲也有疫情报告。

The strategy of the Medical Research Council is to improve the progress of international health research worldwide. Vaccination has had an enormous impact on human and animal health and is therefore one of the most important and effective medical interventions. However, there are still many examples of diseases for which we do not have effective vaccines. Furthermore, much of our current vaccine production involves the production of disease-causing agents (e.g. viruses) which are subsequently inactivated during the production process. In their simplest terms, viruses can be thought of as protein containers that protect the viral genetic material inside. The container is inert - it is the viral genetic material inside which is responsible for causing disease. However, the container (capsid) is of key importance in the process of developing immunity through vaccination. Here, the body's immune system recognises the capsid proteins and generates antibodies to these, which then give the body protection against the disease. Therefore, production of just the capsid as a virus-like particle (VLP) should elicit a protective immune response, yet be totally safe. Furthermore, such production could be undertaken under low containment, which is both easier and cheaper, thus making such virus-like particle vaccines more accessible to developing countries. However, there are problems to be overcome, as many VLPs are unstable. We have a large amount of proof-of-principle data with the production of VLPs for poliovirus and have generated stabilised VLPs that offer better protection than the current polio vaccine (in animal models). We now we wish to apply our strategy to other viruses, focussing on the causative agents of hand, foot and mouth disease. This is a disease of growing concern due to outbreaks particularly in the SE Asia region, associated with hospitalisation and death. According to the World Health Organisation, this affected 1,520,274 people by the end of July in 2012 in China, with 431 reported deaths, and outbreaks are now reported in Europe.