Journal
VACCINE
Volume 37, Issue 26, Pages 3426-3434Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2019.05.018
Keywords
Adjuvant; Flagellin; VLP; Influenza; CD4 T cells
Categories
Funding
- NIH/NIAID [AI105170, AI134132, AI093772]
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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. (C) 2019 Elsevier Ltd. All rights reserved.
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