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AbstractAntigenic targets of influenza vaccination are currently seen to be polarised between (i) highly immunogenic (and protective) epitopes of high variability, and (ii) conserved epitopes of low immunogenicity. This requires vaccines directed against the variable sites to be continuously updated, with the only other alternative being seen as the artificial boosting of immunity to invariant epitopes of low natural efficacy. However, theoretical models suggest that the antigenic evolution of influenza is best explained by postulating the existence of highly immunogenic epitopes of limited variability. Here we report the identification of such an epitope of limited variability in the head domain of the H1 haemagglutinin protein. We show that the epitope mediates immunity to historical influenza strains not previously seen by a cohort of young children. Furthermore, vaccinating mice with these epitope conformations can induce immunity to all the human H1N1 influenza strains that have circulated since 1918. The identification of epitopes of limited variability offers a mechanism by which a universal influenza vaccine can be created; these vaccines would also have the potential to protect against newly emerging influenza strains.

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