Protection by universal influenza vaccine is mediated by memory CD4 T cells.

•A vaccinia-based universal influenza vaccine was previously developed by us.•Influenza virus-specific CD4+ T cells were found to be important for protection.•Vaccine-induced memory CD4+ T cells were needed for early antibody production.•Vaccine-induced memory CD4+ T cells were needed for early CD8+ recall responses.•Human influenza-specific T cells could be recruited and expanded by the vaccine.