Characterization and Immunogenicity of Influenza H7N9 Vaccine Antigens Produced Using a Serum-Free Suspension MDCK Cell-Based Platform

Viruses. 2022 Aug 31;14(9):1937. doi: 10.3390/v14091937.

Abstract

Human infections with avian-origin H7N9 influenza A viruses were first reported in China, and an approximately 38% human mortality rate was described across six waves from February 2013 to September 2018. Vaccination is one of the most cost-effective ways to reduce morbidity and mortality during influenza epidemics and pandemics. Egg-based platforms for the production of influenza vaccines are labor-intensive and unable to meet the surging demand during pandemics. Therefore, cell culture-based technology is becoming the alternative strategy for producing influenza vaccines. The current influenza H7N9 vaccine virus (NIBRG-268), a reassortant virus from A/Anhui/1/2013 (H7N9) and egg-adapted A/PR/8/34 (H1N1) viruses, could grow efficiently in embryonated eggs but not mammalian cells. Moreover, a freezing-dry formulation of influenza H7N9 vaccines with long-term stability will be desirable for pandemic preparedness, as the occurrence of influenza H7N9 pandemics is not predictable. In this study, we adapted a serum-free anchorage-independent suspension Madin-Darby Canine Kidney (MDCK) cell line for producing influenza H7N9 vaccines and compared the biochemical characteristics and immunogenicity of three influenza H7N9 vaccine antigens produced using the suspension MDCK cell-based platform without freeze-drying (S-WO-H7N9), the suspension MDCK cell-based platform with freeze-drying (S-W-H7N9) or the egg-based platform with freeze-drying (E-W-H7N9). We demonstrated these three vaccine antigens have comparable biochemical characteristics. In addition, these three vaccine antigens induced robust and comparable neutralizing antibody (NT; geometric mean between 1016 and 4064) and hemagglutinin-inhibition antibody (HI; geometric mean between 640 and 1613) titers in mice. In conclusion, the serum-free suspension MDCK cell-derived freeze-dried influenza H7N9 vaccine is highly immunogenic in mice, and clinical development is warranted.

Keywords: immunogenicity; influenza H7N9 vaccine; suspension MDCK cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Dogs
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins
  • Humans
  • Influenza A Virus, H1N1 Subtype*
  • Influenza A Virus, H7N9 Subtype*
  • Influenza Vaccines*
  • Influenza, Human* / prevention & control
  • Madin Darby Canine Kidney Cells
  • Mice

Substances

  • Antibodies, Neutralizing
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins
  • Influenza Vaccines

Grants and funding

The research was supported by the National Health Research Institutes, Taiwan, the Ministry of Health and Welfare, Taiwan, and the Minister of Science and Technology, Taiwan (grant # 110-2327-B-400-004).