Different immunity elicited by recombinant H5N1 hemagglutinin proteins containing pauci-mannose, high-mannose, or complex type N-glycans

• Published in: PloS one Vol. 8; no. 6; p. e66719
• Main Authors: Lin, Shih-Chang, Jan, Jia-Tsrong, Dionne, Ben, Butler, Michael, Huang, Ming-Hsi, Wu, Chung-Yi, Wong, Chi-Huey, Wu, Suh-Chin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14-06-2013; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Antibody-Producing Cells - metabolism; Antigen-Presenting Cells - immunology; Antigens; Avian flu; Avian influenza; B cells; Biology; Carbohydrate Conformation; Carbohydrate Sequence; Cell culture; CHO Cells; Chromatography; Cloning; Cricetinae; Cricetulus; Dendritic cells; Deoxyribonucleic acid; DNA; Epidemics; Female; Galactose; Gene amplification; Genomics; Glycosylation; Health aspects; Hemagglutinins; Hemagglutinins - chemistry; Hemagglutinins - immunology; Hemagglutinins - metabolism; Humans; Immune response; Immune system; Immunity; Immunization; Immunoglobulin Isotypes - blood; Immunoglobulins; Immunologic factors; Influenza; Influenza A Virus, H5N1 Subtype - immunology; Influenza vaccines; Influenza Vaccines - chemistry; Influenza Vaccines - immunology; Influenza Vaccines - metabolism; Influenza viruses; Influenza, Human - immunology; Influenza, Human - prevention & control; Influenza, Human - virology; Insect cells; Insects; Mammalian cells; Mammals; Mannans - metabolism; Mannose; Mathematics; Medicine; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Sequence Data; Molecular weight; Monosaccharides; Mortality; N-glycans; Neutralization; Pandemics; Polysaccharides; Protein expression; Protein Processing, Post-Translational; Protein Structure, Tertiary; Proteins; Sf9 Cells; Spodoptera; T-Lymphocytes - immunology; Vaccination; Vaccine development; Vaccines; Viral envelope proteins; Viral Proteins - chemistry; Viral Proteins - immunology; Viral Proteins - metabolism; Virus diseases; Viruses; Canada; Manitoba Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0066719

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.