Introduction: High variance is associated with influenza vaccine effectiveness (VE). Accumulating evidence suggests that preexisting influenza-specific immunity results in the variance in VE and skews overall immune response to vaccination. Nevertheless, the investigation of preexisting immunity is highly limited due to the lack of proper methodology to explore the complex individual immune history.Areas covered: Retrospective observational studies have shown that the preexisting influenza specific immunity influences on VE. To simplify a discussion, we summarized important findings from the observational studies based on the transition of the individual immune history: the first exposure to influenza virus, the first vaccination, and repetitive exposure throughout life. We also discussed the prospectus of pre-immunized animal models to investigate the interaction between preexisting immunity and vaccine efficacy.Expert opinion: A better understanding in the underlying mechanisms on preexisting immunity is critical to improve VE and to help develop novel vaccine strategies. Using animals pre-immunized with historical influenza strains is a promising approach to verify the underlying immunologic mechanism of interaction between preexisting immunity and vaccine antigen. Also, pre-immunized animal models will be better able to evaluate the efficacy of novel vaccine strategies than naïve animals.
Keywords: Seasonal influenza vaccine effectiveness; immune imprinting; interference among repeated vaccinations; pre-immune animal model; preexisting influenza specific-immunity.