Towards pandemic influenza vaccines

随着最近亚洲患者及其与禽流感H5N1病毒分离的密切接触者的死亡，世界突然对大流行性流感的威胁发出了警告。专家认为，这种病毒变异并获得在人类群体中迅速传播的能力只是个时间问题。目前可用的疫苗几乎没有能力预防感染一种新的大流行病毒。一旦病毒袭来，就可以制造出合适的疫苗来对抗它，但这个过程至少需要6个月，这是病毒已经在全球传播的预测时间。我们建议，一种旨在诱导针对所有流感病毒共有的保守区的杀伤T细胞(称为CTL)的疫苗可以用作预防措施，而不需要事先知道将出现的确切病毒类型。这种疫苗不能预防感染，但会大大减轻疾病的严重性。我们已经设计了一种疫苗，这种疫苗可以诱导高水平的CTL，当在动物模型中进行测试时，可以极大地加快清除目前人类种群中的这种类型的病毒。然而，我们预测，一种新的大流行病毒的生长将更加强劲，因此我们的疫苗将不得不改进以应对这种情况。这个项目着眼于增加我们的疫苗诱导的CTL的数量和有效性的方法。这将需要了解我们如何调节其他特殊细胞、树突状细胞和辅助T细胞的功能，这些细胞在启动和维持CTL反应以及调节CTL本身方面发挥作用。

The world has suddenly been alerted to the threat of pandemic influenza with the recent deaths in Asia of patients and their close contacts from which the avian influenza H5N1 virus has been isolated. Experts believe that it is only a matter of time before this virus mutates and acquires the ability to rapidly spread within the human population. The currently available vaccines have virtually no capacity to prevent infection by a new pandemic virus. Once the virus strikes appropriate vaccines can be made against it but this procedure takes at least 6 months, the time predicted for the virus to have already spread throughout the globe. We are proposing that a vaccine designed to induce killer T cells (called CTLs) that target the conserved regions shared by all influenza viruses, could be used as a preventative measure without prior knowledge of the exact type of virus that will emerge. This sort of vaccine will not prevent against infection but will greatly lessen the severity of the disease. We have already designed a vaccine that that will induce high levels of CTLs that can greatly speed up the clearance of viruses of the type that are currently in the human population, when tested in animal models. However, we predict that a new pandemic virus will be much more vigorous in its growth and so our vaccines will have to be improved to cope with this. This project looks at ways of increasing the number and effectiveness of the CTLs that are induced by our vaccines. This will require an understanding of how we can modulate the function of other specialised cells, dendritic cells and helper T cells, that play a role in starting and maintaining the CTL response, as well as modulating the CTLs themselves.