Evaluation of MDCK cell-derived influenza H7N9 vaccine candidates in ferrets

PLoS One. 2015 Mar 23;10(3):e0120793. doi: 10.1371/journal.pone.0120793. eCollection 2015.

Abstract

Avian-origin influenza A (H7N9) viruses emerged as human pathogens in China in early 2013 and have killed >100 persons. Influenza vaccines are mainly manufactured using egg-based technology which could not meet the surging demand during influenza pandemics. In this study, we evaluated cell-based influenza H7N9 vaccines in ferrets. An egg-derived influenza H7N9 reassortant vaccine virus was adapted in MDCK cells. Influenza H7N9 whole virus vaccine antigen was manufactured using a microcarrier-based culture system. Immunogenicity and protection of the vaccine candidates with three different formulations (300 μg aluminum hydroxide, 1.5 μg HA, and 1.5 μg HA plus 300 μg aluminum hydroxide) were evaluated in ferrets. In ferrets receiving two doses of vaccination, geometric mean titers of hemagglutination (HA) inhibition and neutralizing antibodies were <10 and <40 for the control group (adjuvant only), 17 and 80 for the unadjuvanted (HA only) group, and 190 and 640 for the adjuvanted group (HA plus adjuvant), respectively. After challenge with wild-type influenza H7N9 viruses, virus titers in respiratory tracts of the adjuvanted group were significantly lower than that in the control, and unadjuvanted groups. MDCK cell-derived influenza H7N9 whole virus vaccine candidate is immunogenic and protective in ferrets and clinical development is highly warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological
  • Animals
  • Antigens, Viral / immunology
  • Dogs
  • Female
  • Ferrets*
  • Immunization
  • Influenza A Virus, H7N9 Subtype / immunology*
  • Influenza A Virus, H7N9 Subtype / ultrastructure
  • Influenza Vaccines / immunology*
  • Lung / immunology
  • Lung / pathology
  • Lung / virology
  • Madin Darby Canine Kidney Cells
  • Orthomyxoviridae Infections / prevention & control*
  • Reassortant Viruses

Substances

  • Antigens, Viral
  • Influenza Vaccines

Grants and funding

This study was funded by the Ministry of Health and Welfare, Taiwan (grant no. MOHW102-TD-B-111-V002) and National Health Research Institutes, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.