Summary Objectives: Hemagglutination inhibiting (HI) antibodies correlate with influenza\nvaccine protection but their association with protection induced by natural infection has\nreceived less attention and was studied here.\nMethods: 940 people from 270 unvaccinated households participated in active ILI surveillance\nspanning 3 influenza seasons. At least 494 provided paired blood samples spanning each season.\nInfluenza infection was confirmed by RT-PCR on nose/throat swabs or serum HI assay conversion.\nResults: Pre-season homologous HI titer was associated with a significantly reduced risk of\ninfection for H3N2 (OR 0.61, 95%CI 0.44e0.84) and B (0.65, 95%CI 0.54e0.80) strains, but not H1N1 strains, whether re-circulated (OR 0.90, 95%CI 0.71e1.15), new seasonal (OR 0.86,\n95%CI 0.54e1.36) or pandemic H1N1-2009 (OR 0.77, 95%CI 0.40e1.49). The risk of seasonal\nand pandemic H1N1 decreased with increasing age (both p < 0.0001), and the risk of pandemic\nH1N1 decreased with prior seasonal H1N1 (OR 0.23, 95%CI 0.08e0.62) without inducing measurable\nA/California/04/2009-like titers.\nConclusions: While H1N1 immunity was apparent with increasing age and prior infection, the\neffect of pre-season HI titer was at best small, and weak for H1N1 compared to H3N2 and B.\nAntibodies targeting non-HI epitopes may have been more important mediators of infectionneutralizing\nimmunity for H1N1 compared to other subtypes in this setting.
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