Multi-subtype influenza virus-like particles incorporated with flagellin and granulocyte-macrophage colony-stimulating factor for vaccine design

• Published in: Antiviral research 2016-09, Vol.133, p.110-118
• Main Authors: Liu, Wen-Chun, Liu, Ying-Yu, Chen, Ting-Hsuan, Liu, Chia-Chyi, Jan, Jia-Tsrong, Wu, Suh-Chin
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic; Animals; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Disease Models, Animal; Female; Flagellin - immunology; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Humans; Immunization; Influenza; Influenza A virus - classification; Influenza A virus - immunology; Influenza Vaccines - immunology; Mice; Multi-subtype vaccine; Neuraminidase - immunology; Neutralization Tests; Orthomyxoviridae - classification; Orthomyxoviridae - immunology; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Salmonella typhimurium; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Vaccines, Virus-Like Particle - immunology; Vaccines, Virus-Like Particle - ultrastructure; Virus-like particle
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2016.07.021

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. •Virus-like particle (VLP) technology for influenza vaccine development.•Molecular adjuvants of flaggellin and GM-CSF to enhance VLP immunogenicity.•Multi-subtype VLPs containing seasonal influenza (H1) and avian influenza (H5 and H7).