Abstract
The 2009 swine-origin pandemic H1N1 (pH1N1) influenza virus transmitted and caused disease in many individuals immune to pre-2009 H1N1 influenza virus. Whilst extensive studies on antibody-mediated pH1N1 cross-reactivity have been described, few studies have focused on influenza-specific memory T-cells. To address this, the immune response in pre-2009 H1N1 influenza-immune mice was evaluated after pH1N1 challenge and disease pathogenesis was determined. The results show that despite homology shared between pre-2009 H1N1 and pH1N1 strains, the effector memory T-cell response to pre-2009 H1N1 was generally ineffective, a finding that correlated with lung virus persistence. Additionally, pH1N1 challenge generated T-cells reactive to new pH1N1 epitopes. These studies highlight the importance of vaccinating against immunodominant T-cell epitopes to provide for a more effective strategy to control influenza virus through heterosubtypic immunity.