Influenza vaccination strategies targeting the hemagglutinin stem region

Influenza is one of the best examples of highly mutable viruses that are able to escape immune surveillance. Indeed, in response to influenza seasonal infection or vaccination, the majority of the induced antibodies are strain-specific. Current vaccine against the seasonal strains with the strategy of surveillance-prediction-vaccine does not cover an unmet virus strain leading to pandemic. Recently, antibodies targeting conserved epitopes on the hemagglutinin (HA) protein have been identified, albeit rarely, and they often showed broad protection. These antibody discoveries have brought the feasibility to develop a universal vaccine. Most of these antibodies bind the HA stem domain and accumulate in the memory B cell compartment. Broadly reactive stem-biased memory responses were induced by infection with antigenically divergent influenza strains and were able to eradicate these viruses, together indicating the importance of generating memory B cells expressing high-quality anti-stem antibodies. Here, we emphasize recent progress in our understanding of how such memory B cells can be generated and discuss how these advances may be relevant to the quest for a universal influenza vaccine.