Seasonal Influenza Can Poise Hosts for CD4 T-Cell Immunity to H7N9 Avian Influenza

The emergence of avian H7N9 viruses has raised concerns about its pandemic potential and prompted vaccine trials. At present, it is unknown whether there will be sufficient cross-reactive hemagglutinin (HA)–specific CD4 T-cell memory with seasonal influenza to facilitate antibody production to H7 HA. There has also been speculation that H7N9 will have few CD4 T-cell epitopes. In this study, we quantified the potential of seasonal influenza to provide memory CD4 T cells that can cross-reactively recognize H7 HA–derived peptides. These studies have revealed that many humans have substantial H7-reactive CD4 T cells, whereas up to 40% are lacking such reactivity. Correlation studies indicate that CD4 T cells reactive with H7 HA are drawn from reactivity generated from seasonal strains. Overall, our findings suggest that previous exposure of humans to seasonal influenza can poise them to respond to avian H7N9, but this is likely to be uneven across populations.