The use of human monoclonal antibodies to inform and enhance influenza vaccine virus selection.

流感感染每年造成重大的疾病和死亡负担（全世界每年有超过250，000人死亡）。减少流感引起的疾病的最有效方法是接种疫苗。流感病毒每年通过改变其表面蛋白来进化，以响应来自人类抗体反应的选择压力。世界卫生组织协调了一项大规模的努力，以监测世界各地流感的演变，试图确定未来几年最有可能导致感染的病毒，并选择最佳候选人制造疫苗。这种方法既有新的，通过对病毒基因进行测序来监测基因变化，也有旧的，通过测试雪貂对候选疫苗病毒产生的抗体与循环毒株的交叉反应性。传统上使用雪貂抗体，因为这些动物以类似于人类的方式对流感感染易感。总体而言，通过这些方法选择的疫苗的有效性（降低患流感的风险）相当差，约为54%，因此还有改进的余地。最近的技术发展提供了一种使用人单克隆抗体分析流感演变的新方法。正是这些人类抗体被认为是推动流感在自然界中进化的原因。我们已经证明，从接种疫苗或感染的个体中分离出的人类抗体可以检测到雪貂抗体错过的病毒变化。此外，人类抗体检测到的变化经常与目前在人群中传播的流感病毒中出现的变化相关。我们建议开发人类单克隆抗体组，以帮助预测病毒的未来演变，这些抗体将分发给世界各地的世卫组织合作中心，与标准雪貂抗体进行比较，以了解这项新技术是否可以改善疫苗选择。

Influenza infections each year cause a major burden of sickness and death (greater than 250,000 deaths each year world wide). The most effective means of reducing illness caused by influenza is by vaccination. The influenza virus evolves by changing its surface proteins each year in response to selective pressure from the human antibody response. The World Health Organisation coordinates a massive effort to monitor the evolution of influenza around the world to try and identify the viruses that are most likely to cause infections in the coming years, and select the best candidates for manufacture into a vaccine. The methods used to do this are both new, by sequencing virus genes to monitor genetic changes, and old, by testing the antibodies that ferrets make to candidate vaccine viruses for cross-reactivity with circulating strains. Ferret antibodies are traditionally used because these animals are susceptible to influenza infections in a way similar to humans. Overall the effectiveness (reduction in risk of becoming ill with influenza) of the vaccines selected by these methods is quite poor at ~54%, so there is room for improvement. Recent technical developments have provided a new method to analyse the evolution of influenza that uses human monoclonal antibodies. It is these human antibodies that are thought to be driving the evolution of influenza in nature. We have shown that human antibodies isolated from vaccinated or infected individuals can detect changes in the virus that the ferret antibodies miss. In addition the changes that human antibodies detect frequently correlate with the changes that are appearing in the influenza viruses currently circulating in the human population. We propose to develop panels of human monoclonal antibodies that can help predict the future evolution of the virus, which will be distributed to the WHO Collaborating Centres around the world, for comparison to the standard ferret antibodies to see if this new technology can improve vaccine selection.