Development of influenza live vaccine by reverse genetics

流感病毒是鸟类和哺乳动物（包括人类）具有高度传染性的呼吸道病原体。它通常在人类中产生显著的流动性和死亡率。目前针对流感病毒的免疫方法包括父母接种灭活流感病毒疫苗，这减少了健康受试者临床疾病的发病率。但在某些情况下，使用灭活疫苗进行免疫接种与保护率非常低或保护期很短有关。另一种有希望的疫苗接种方法是使用减毒活流感病毒。这些疫苗在正在进行的临床试验中显示出相当大的希望。然而，令人关注的是，发病机制在它们的复制过程中发生了恢复。我们提出了一种设计活病毒疫苗的替代方法，这种方法依赖于对负责离子通道活性的甲型流感病毒M2蛋白的改变。它在细胞培养中没有表现出明显的生长缺陷，但在小鼠中生长减弱。研究表明，这种M2离子通道缺陷突变病毒可以保护小鼠免受致命剂量流感病毒的攻击，这表明在流感活疫苗中加入这种M2变异作为一种减毒突变的潜力。

Influenza virus is a highly infectious respiratory pathogen of birds and mammals, including human. It often produces significant mobidity and mortality in humans. Current methods of immunization against influenza virus include parental administration of inactivated influenza virus vaccines, which reduces the incidence of clinical illness in healthy subjects. But in some cases, immunization with inactivated vaccines is associated with very low protection rates or short protection periods.Another promising approach to vaccination is the use of live-attenuated influenza viruses. Theses vaccines have shown considerable promise in ongoing clinical trials. However, it has been concerned that the pathogenesis happened to recovered during their replication.We propose an alternative approach to the design of live virus vaccines, one that relies on alteration of the influenza A virus M2 protein which is responsible for ion channel activity. It did not show appreciable growth defect in cell culture, although its growth was attenuated in mice. It has shown that this M2 ion channel defective mutant virus protected mice against challenge with lethal doses of influenza virus, indicating the potential or incorporating this M2 alteration in a live influenza vaccine as one of the attenuating mutations.