Differential Induction of Interferon Stimulated Genes by Cell-based Versus Egg-based Quadrivalent Influenza Vaccines in Children During the 2018-19 Season.

Cell-based quadrivalent inactivated influenza vaccine has been shown to have higher vaccine effectiveness than traditional egg-based quadrivalent inactivated influenza vaccine. This is observed despite similar levels of serum hemagglutinin antibodies induced by each vaccine. Here, we examine peripheral immune activation following egg-based or cell-based influenza vaccination in a clinical trial in children. Peripheral blood mononuclear cells were isolated and RNA sequenced from 81 study participants (41 Fluzone, egg-based and 40 Flucelvax, cell based) pre- and 7 days post- vaccination. Seroconversion was assessed by hemagglutinin inhibition assay. Differential gene expression was determined and pathway analysis was conducted. Cell-based influenza vaccine induced greater interferon stimulated and innate immune gene activation compared with egg-based influenza vaccine. Participants who seroconverted had increased interferon signaling activation versus those who did not seroconvert. These data suggest that cell-based influenza vaccine stimulates immune activation differently from egg-based influenza vaccine, shedding light on reported differences in vaccine effectiveness.