title: Multi-subtype influenza virus-like particles incorporated with flagellin and granulocyte-macrophage colony-stimulating factor for vaccine design.
abstract: Virus-like particle (VLP) technology is an attractive platform for seasonal and pandemic influenza vaccine development. We previously showed that influenza VLPs can be modified using M2 fusion with molecular adjuvants such as Salmonella typhimurium flagellin (FliC) to enhance VLP immunogenicity. For this study, three types of chimeric VLPs were incorporated with FliC, granulocyte-macrophage colony-stimulating factor (GM-CSF), or both GM-CSF and FliC (GM-CSF/FliC) to enhance anti-influenza immunogenicity. Our results indicate that immunizations with the chimeric FliC VLPs and GM-CSF/FliC H5N1 VLPs elicited more potent and broadly neutralizing antibodies and neuraminidase-inhibiting antibodies in sera, and induced higher numbers of hemagglutinin-specific antibody-secreting cells and germinal center B cell subsets in splenoctyes. Immunization with the chimeric GM-CSF H5N1 VLPs induced stronger Th1 and Th2 cellular responses. The chimeric GM-CSF/FliC H5N1 VLP constructs were further obtained to include H7 or H1H7 bi- or tri-subtype. It is our hope that these findings provide useful information for developing multi-subtype influenza vaccines.
authors.affiliation: Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Liu
authors.affiliation: Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Liu
authors.affiliation: Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Ting-Hsuan
authors.initials: TH
authors.lastname: Chen
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Chia-Chyi
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Jia-Tsrong
authors.initials: JT
authors.lastname: Jan
authors.affiliation: Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan; Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan. Electronic address: scwu@mx.nthu.edu.tw.
authors.forename: Suh-Chin
authors.initials: SC
authors.lastname: Wu
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005408:Flagellin / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007114:Immunization; D009980:Influenza A virus / Q000145:classification / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D009439:Neuraminidase / Q000276:immunology; D009500:Neutralization Tests; D009975:Orthomyxoviridae / Q000145:classification / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D058425:Vaccines, Virus-Like Particle / Q000276:immunology* / Q000648:ultrastructure
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D058425:Vaccines, Virus-Like Particle; D005408:Flagellin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009439:Neuraminidase
keywords: Influenza; Multi-subtype vaccine; Virus-like particle