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H1N1 influenza causes substantial seasonal illness and was the subtype of the2009 influenza pandemic. Precise measures of antigenic distance between thevaccine and circulating virus strains help researchers design influenzavaccines with high vaccine effectiveness. We here introduce a sequence-basedmethod to predict vaccine effectiveness in humans. Historical epidemiologicaldata show that this sequence-based method is as predictive of vaccineeffectiveness as hemagglutination inhibition (HI) assay data from ferret animalmodel studies. Interestingly, the expected vaccine effectiveness is greateragainst H1N1 than H3N2, suggesting a stronger immune response against H1N1 thanH3N2. The evolution rate of hemagglutinin in H1N1 is also shown to be greaterthan that in H3N2, presumably due to greater immune selection pressure.

A Novel Sequence-Based Antigenic Distance Measure for H1N1, with Application to Vaccine Effectiveness and the Selection of Vaccine Strains