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.
Sonnberg, S., Webby, R.J., Webster, R.G., 2013. Natural history of highly pathogenicavian influenza H5N1. Virus Res. 178, 63e77.
Krammer, F., Palese, P., 2015. Advances in the development of influenza virus vaccines. Nat. Rev. Drug Discov. 14, 167e182.
Lopez-Macias, C., 2012. Virus-like particle (VLP)-based vaccines for pandemic influenza: performance of a VLP vaccine during the 2009 influenza pandemic. Hum. Vaccin Immunother. 8, 411e414.
Ross, T.M., Mahmood, K., Crevar, C.J., Schneider-Ohrum, K., Heaton, P.M., Bright, R.A., 2009. A trivalent virus-like particle vaccine elicits protective immune responses against seasonal influenza strains in mice and ferrets. PLoS One 4, e6032.
Wei, H.J., Chang,W., Lin, S.C., Liu,W.C., Chang, D.K., Chong, P., et al., 2011. Fabrication of influenza virus-like particles using M2 fusion proteins for imaging single viruses and designing vaccines. Vaccine 29, 7163e7172.
Funding 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).
Credits: None available.
You must be logged in and own this product in order to