Dataset Information

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.

ABSTRACT: 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.

SUBMITTER: Ko EJ

PROVIDER: S-EPMC7274143 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Ko Eun-Ju EJ Lee Youri Y Lee Young-Tae YT Jung Yu-Jin YJ Ngo Vu L VL Kim Min-Chul MC Kim Ki-Hye KH Wang Bao-Zhong BZ Gewirtz Andrew T AT Kang Sang-Moo SM

Vaccine 20190514 26

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 h ...[more]

PMID: 31101421

Similar Datasets

Project description:Background: Vaccination is commonly used to prevent and control influenza infection in humans. However, improvements in the ease of delivery and strength of immunogenicity could markedly improve herd immunity. The aim of this pre-clinical study is to test the potential improvements to existing intranasal delivery of formalin-inactivated whole Influenza A vaccines (WIV) by formulation with a cationic lipid-based adjuvant (N3). Additionally, we combined WIV and N3 with a DNA-encoded TLR5 agonist secreted flagellin (pFliC(-gly)) as an adjuvant, as this adjuvant has previously been shown to improve the effectiveness of plasmid-encoded DNA antigens. Methods: Outbred and inbred mouse strains were intranasally immunized with unadjuvanted WIV A/H1N1/SI 2006 or WIV that was formulated with N3 alone. Additional groups were immunized with WIV and N3 adjuvant combined with pFliC(-gly). Homo and heterotypic humoral anti-WIV immune responses were assayed from serum and lung by ELISA and hemagglutination inhibition assay. Homo and heterotypic cellular immune responses to WIV and Influenza A NP were also determined. Results: WIV combined with N3 lipid adjuvant the pFliC(-gly) significantly increased homotypic influenza specific serum antibody responses (>200-fold), increased the IgG2 responses, indicating a mixed Th1/Th2-type immunity, and increased the HAI-titer (>100-fold). Enhanced cell-mediated IFNγ secreting influenza directed CD4+ and CD8+ T cell responses (>40-fold) to homotypic and heterosubtypic influenza A virus and peptides. Long-term and protective immunity was obtained. Conclusions: These results indicate that inactivated influenza virus that was formulated with N3 cationic adjuvant significantly enhanced broad systemic and mucosal influenza specific immune responses. These responses were broadened and further increased by incorporating DNA plasmids encoding FliC from S. typhimurum as an adjuvant providing long lasting protection against heterologous Influenza A/H1N1/CA09pdm virus challenge.

Dataset Information

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.

Publications

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets