Differential Induction of Interferon-Stimulated Genes by Cell-Based Versus Egg-Based Quadrivalent Influenza Vaccines in Children During the 2018-2019 Season

Background 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.Methods In this study, we examine peripheral immune activation after egg-based or cell-based influenza vaccination in a clinical trial in children. Peripheral blood mononuclear cells were isolated, and ribonucleic acid was sequenced from 81 study participants (41 Fluzone, egg based and 40 Flucelvax, cell based) pre- and 7 days postvaccination. Seroconversion was assessed by hemagglutinin inhibition assay. Differential gene expression was determined and pathway analysis was conducted.Results 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.Conclusions 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. Despite similar antibody response, cell-based influenza vaccine induces a distinct transcriptomic response compared with egg-based vaccine. Cell-based influenza vaccination stimulates increased interferon-induced gene expression, which tracks with vaccine-induced seroconversion, regardless of vaccine type.