The negative effect of pre-existing immunity on influenza vaccine responses transcends the impact of vaccine formulation type and vaccination history.

The most effective measure to induce protection from influenza is vaccination. Thus, yearly vaccination is recommended, which, together with infections, establishes diverse repertoires of B cells, antibodies and T cells. Here, we examined the impact of this accumulated immunity on human responses of adults to split, subunit and recombinant protein-based influenza vaccines. ELISA assays, used to quantify serum antibodies and peptide-stimulated CD4 T cell cytokine ELISpots, revealed that pre-existing levels of HA-specific antibodies were negatively associated with gains in antibody post-vaccination, while pre-existing levels of CD4 T cells were negatively correlated with vaccine-induced expansion of CD4 T cells. These patterns were seen independently of the vaccine formulation administered and the subjects' influenza vaccine history. Thus, although memory CD4 T cells and serum antibodies consist of components that can enhance vaccine responses, on balance, the accumulated immunity specific for influenza A H1 and H3 proteins is associated with diminished future responses.