Improving immunogenicity of influenza virus H7N9 recombinant hemagglutinin for vaccine development

• Published in: Vaccine Vol. 37; no. 13; pp. 1897 - 1903
• Main Authors: Ting-Hui-Lin, Chia, Min-Yuan, Lin, Chun-Yang, Yeh, Yi-Qi, Jeng, U-Ser, Wu, Wen-Guey, Lee, Min-Shi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 22.03.2019; Elsevier BV; Elsevier Limited
• Subjects: Amino acids; Animals; Antibodies, Neutralizing; Antibodies, Viral; Antigens; Avian flu; Baculoviridae; Baculovirus; Chromatography; Construction; Crosslinking; Eggs; Female; Gene Expression; Glycerol; H7N9; Hemagglutination Inhibition Tests; Hemagglutinin; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins; human diseases; Humans; Immunization; Immunogenicity; Immunogenicity, Vaccine; Infections; Influenza; Influenza A; Influenza A virus; Influenza A Virus, H7N9 Subtype; Influenza vaccine; Influenza Vaccines; Influenza, Human; Insects; Medical research; Mice; neutralizing antibodies; pandemic; Pandemics; Proteins; Recombinant Proteins; Research centers; Stability analysis; Stability tests; Thermal stability; Transmembrane domain; Vaccine development; Vaccines; Viruses; Taiwan; Transmembrane domain; H7N9; Hemagglutinin; Influenza vaccine
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2018.09.034

•Human H7N9 HA was produced in an artificial soluble construct could not maintain trimer state and unstable at 4 °C storage.•Highly order oligo conformation-mH7 (membrane form H7) has better stability and immunogenicity.•The mH7 is a desirable candidate for vaccine development to prepare for pandemic flu. Human infections of novel avian influenza A virus (H7N9) emerged in early 2013 and caused about 40% case-fatality through 2017. Therefore, development of influenza H7N9 vaccines is critical for pandemic preparedness. Currently, there are three means of production of commercial influenza vaccines: egg-based, mammalian cell-based, and insect cell-based platforms. The insect cell-based platform has the advantage of high speed in producing recombinant protein. In this study, we evaluate the stability and immunogenicity of two different influenza H7 HA expression constructs generated using the baculovirus system, including membrane-based full-length HA (mH7) and secreted ectodomain-based H7 (sH7). The mH7 construct could form an oligomer-rosette structure and had a high hemagglutinin (HA) titer 8192. In contrast to mH7, the sH7 construct could not form an oligomer-rosette structure and did not have HA titer before cross-linking with anti-His antibody. Thermal stability tests showed that the sH7 and mH7 constructs were unstable at 43 °C and 52 °C, respectively. In a mice immunization study, the mH7 construct but not the sH7 construct could induce robust HI and neutralizing antibody titers. In conclusion, further development of the mH7 vaccine candidate is desirable.