Heads, stalks and everything else: how can antibodies eradicate influenza as a human disease?

Current seasonal influenza virus vaccines are effective against infection but they have to be reformulated on a regular basis to counter antigenic variations. The majority of the antibodies induced in response to seasonal vaccination are strain specific. However, antibodies targeting conserved epitopes on the hemagglutinin protein have been identified and they offer broad protection. Most of these antibodies bind the hemagglutinin stalk domain and are generated from preexisting memory B cells. Broadly protective stalk-biased responses induced by antigenically divergent influenza strains, in concert with prior immunity, are sufficient to eradicate seasonally circulating strains. Future vaccine trials should aim to harness and maintain such a response with the realistic goal of developing a universal influenza vaccine.