Different Immunity Elicited by Recombinant H5N1 Hemagglutinin Proteins Containing Pauci-Mannose,High-Mannose,or Complex Type N-Glycans |
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| Authors: | Shih-Chang Lin Jia-Tsrong Jan Ben Dionne Michael Butler Ming-Hsi Huang Chung-Yi Wu Chi-Huey Wong Suh-Chin Wu |
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| Institution: | 1. Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.; 2. Genomics Research Center, Academia Sinica, Taipei, Taiwan.; 3. Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.; 4. National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan.; McGill University, Canada, |
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| Abstract: | Highly pathogenic avian influenza H5N1 viruses can result in poultry and occasionally in human mortality. A safe and effective H5N1 vaccine is urgently needed to reduce the pandemic potential. Hemagglutinin (HA), a major envelope protein accounting for approximately 80% of spikes in influenza virus, is often used as a major antigen for subunit vaccine development. In this study, we conducted a systematic study of the immune response against influenza virus infection following immunization with recombinant HA proteins expressed in insect (Sf9) cells, insect cells that contain exogenous genes for elaborating N-linked glycans (Mimic) and mammalian cells (CHO). While the antibody titers are higher with the insect cell derived HA proteins, the neutralization and HA inhibition titers are much higher with the mammalian cell produced HA proteins. Recombinant HA proteins containing tri- or tetra-antennary complex, terminally sialylated and asialyated-galactose type N-glycans induced better protective immunity in mice to lethal challenge. The results are highly relevant to issues that should be considered in the production of fragment vaccines. |
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