Flagellin-expressing virus-like particles exhibit adjuvant effects on promoting IgG isotype-switched long-lasting antibody induction and protection of influenza vaccines in CD4-deficient mice.

Incorporation of membrane-anchored flagellin molecules into the surfaces of influenza virus-like particles (VLP) was previously reported to promote T helper (Th) 1-biased IgG antibody production and protective efficacy of co-presented vaccine antigens. Herein, we investigated the potential adjuvant effects and mechanisms of flagellin-expressing VLP (FliC-VLP) as an independent component on influenza vaccination in wild-type and mutant mouse models. FliC-VLP adjuvanted influenza vaccination was highly effective in promoting the induction of Th1-biased IgG isotype switched antibodies, enhanced protection, and long-lasting IgG antibody responses in both wild-type and CD4-knockout mice. In contrast, the adjuvant effects of soluble flagellin were Th2-biased and required CD4 T helper cells. The adjuvant effects of FliC-VLP were less dependent on CD4 T cells and flagellin-mediated innate immune signaling pathways. The results suggest that FliC-VLP might play an effective adjuvant role in an immune competent condition as well as in a defect of CD4 T cells.