Antibodies recognizing the hemagglutinin (HA) protein, which are elicited following infection or vaccination, confer protection against influenza virus infection. Although annual seasonal influenza vaccines provide some protection against currently circulating influenza strains, they lack efficacy against viruses expressing divergent globular head domains of HA. Moreover, antigenic drift within the globular head of circulating viruses necessitates frequent reformulation of the seasonal vaccine, a process that is both expensive and time-consuming. In this regard, vaccine strategies that generate antibodies with reactivity against an array of influenza viral strains could reduce the need for yearly influenza vaccination and increase our preparedness for potential pandemics. In this review, recent progress toward the generation of an influenza vaccine capable of eliciting hemagglutinin specific and broadly protective antibody responses is summarized.
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