高致病性禽流感H5N1病毒的广泛流行对人类社会造成了很大的危害。疫苗是迄今为止最有效的“武器”。然而，该病毒频繁的位点突变所致的抗原变化，容易导致疫苗效果降低甚至失效。系统地理解流感病毒的抗原进化规律对于合理准确地推荐流感疫苗进而提高疫苗的效果非常重要。在本课题中，我们将从高致病性禽流感H5N1病毒的主要抗原蛋白（血凝素）的序列出发，通过发展计算模型对该病毒进行系统的抗原分类，并且采用实验方法对其进行验证。然后基于该抗原分类，在该病毒完整进化历史的尺度上研究它的抗原进化模式及其与时空关联规律，阐明该病毒抗原进化的发生发展过程。最后，我们将系统地研究抗原类演化的分子机制，确定出介导抗原类转变的位点及其作用机理。该课题的实施不仅会促进我们对于禽流感H5N1病毒抗原进化的理解，有利于合理地制定疫苗政策，同时也为防控其他禽流感病毒提供一定的参考。

The threat of widespread highly pathogenic avian influenza (HPAI) H5N1 virus to both poultry industry and human life has tightened the global surveillance of this deadly pathogen. Vaccination is currently the most effective way to prevent its infection. However, the virus could change its antigen rapidly, causing the vaccines ineffective. To improve the performance of vaccines, it is very necessary to understand the antigenic evolution of the virus systematically. In this study, we will develop a computational method to systematically predict antigenic clusters for HPAI H5N1 virus based on the sequence of its surface protein hemagglutinin (HA). Then, the predicted antigenic clustering would be validated with HA-inhibition experiment. Furthermore, the antigenic evolutionary pattern and its spatial-temporal characteristics would be investigated with the validated antigenic clustering. Finally, the molecular mechanisms behind the antigenic evolution would be explored by sequence and structure analysis. This study would deepen our understanding towards the antigenic evolution of HPAI H5N1 virus and help for control and prevention of this deadly virus, which could also have some implications for control of other avian influenza virus.