Virus-like particles presenting flagellin exhibit unique adjuvant effects on eliciting T helper type 1 humoral and cellular immune responses to poor immunogenic influenza virus M2e protein vaccine

Current licensed adjuvants including aluminum hydroxide (alum) bias immune responses toward T helper type 2 (Th2) immune responses. We tested whether virus-like particles presenting flagellin (Flag VLP) exhibit adjuvant effects on eliciting Th1 type immune responses and improving the efficacy of poor immunogenic tandem repeat M2e (M2e5x) protein vaccine against influenza virus. Co-immunization of mice with Flag VLP and M2e5x protein vaccine induced significantly higher levels of IgG2a isotype (Th1) antibodies in sera and mucosal sites, effector CD4+ T cells secreting IFN-γ and granzyme B, and more effective lung viral clearance and protection compared to alum adjuvant. Flag VLP stimulated primary macrophages and dendritic cells to secrete inflammatory cytokines, which is partially dependent on the Toll-like receptor 5. This study provides insight into developing effective vaccine adjuvants.