Toward universal influenza virus vaccines: from natural infection to vaccination strategy.

Conceptually, a universal influenza vaccine should elicit broadly protective antibody responses targeting highly conserved epitope(s) shared by various virus strains. Strategically directing antibody immunity to the conserved hemagglutinin stalk has recently emerged as a promising approach that is substantiated by the identification of naturally occurring, stalk-reactive human antibodies capable of conferring broad protection against influenza virus challenge in animal models. Despite all the advancements, future realization of this strategy still faces many challenges, particularly whether it is able to induce enough of cross-reactive antibody response to protect against pandemic viruses. In this respect, recent in-depth dissections of human immune responses to H7N9 virus and vaccination provide much-needed new insights.