Multi-subtype influenza virus-like particles incorporated with flagellin and granulocyte-macrophage colony-stimulating factor for vaccine design
Wen-Chun Liu1, Ying-Yu Liu1, Ting-Hsuan Chen1, Chia-Chyi Liu2, Jia-Tsrong Jan3,
Suh-Chin Wu1,4 *
1Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan; 2National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan; 3Genomics Research Center, Academia Sinica, Taipei, Taiwan; 4Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan
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 colonystimulating 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.
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This work was supported by Ministry of Science and Technology, Taiwan (MOST 105-2321-B-007-005, MOST 105-2321-B-007-006) and National Tsing Hua University (105N742CV8).