Influenza antigenic drift: what is the driving force?

Influenza virus remains an important human pathogen causing recurring 'flu', largely due to its ability to constantly modify the antigenicity of its major glycoprotein, hemagglutinin (HA), in processes named 'antigenic shift' and 'antigenic drift'. A better understanding of the driving force for antigenic drift is critical for enhancing the effectiveness of annual flu vaccine, which is the primary tool for combating seasonal influenza. With solid experimental data, a recent study published on Science proposed a new antigenic drift model in which receptor binding avidity plays a critical role in influenza antigenic drift. This commentary discusses the new study in the context of historic influenza research and poses a few key questions on antigenic drift that need to be addressed in future research.