Immunogenicity and protective efficacy of a Vero cell culture-derived whole-virus H7N9 vaccine in mice and guinea pigs

PLoS One. 2015 Feb 26;10(2):e0113963. doi: 10.1371/journal.pone.0113963. eCollection 2015.

Abstract

Background: A novel avian H7N9 virus with a high case fatality rate in humans emerged in China in 2013. We evaluated the immunogenicity and protective efficacy of a candidate Vero cell culture-derived whole-virus H7N9 vaccine in small animal models.

Methods: Antibody responses induced in immunized DBA/2J mice and guinea pigs were evaluated by hemagglutination inhibition (HI), microneutralization (MN), and neuraminidase inhibition (NAi) assays. T-helper cell responses and IgG subclass responses in mice were analyzed by ELISPOT and ELISA, respectively. Vaccine efficacy against lethal challenge with wild-type H7N9 virus was evaluated in immunized mice. H7N9-specific antibody responses induced in mice and guinea pigs were compared to those induced by a licensed whole-virus pandemic H1N1 (H1N1pdm09) vaccine.

Results: The whole-virus H7N9 vaccine induced dose-dependent H7N9-specific HI, MN and NAi antibodies in mice and guinea pigs. Evaluation of T-helper cell responses and IgG subclasses indicated the induction of a balanced Th1/Th2 response. Immunized mice were protected against lethal H7N9 challenge in a dose-dependent manner. H7N9 and H1N1pdm09 vaccines were similarly immunogenic.

Conclusions: The induction of H7N9-specific antibody and T cell responses and protection against lethal challenge suggest that the Vero cell culture-derived whole-virus vaccine would provide an effective intervention against the H7N9 virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Antibody Formation
  • Chlorocebus aethiops
  • Female
  • Guinea Pigs
  • Hemagglutination Inhibition Tests
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Immunoglobulin G / analysis
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H1N1 Subtype / physiology
  • Influenza A Virus, H7N9 Subtype / immunology*
  • Influenza A Virus, H7N9 Subtype / physiology
  • Influenza Vaccines / immunology*
  • Interferon-gamma / analysis
  • Interleukin-4 / analysis
  • Mice
  • Mice, Inbred DBA
  • Neuraminidase / antagonists & inhibitors
  • Neuraminidase / metabolism
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / mortality
  • Orthomyxoviridae Infections / prevention & control*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Vero Cells

Substances

  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin G
  • Influenza Vaccines
  • Interleukin-4
  • Interferon-gamma
  • Neuraminidase

Grants and funding

The study was funded by Baxter. Baxter employees were responsible for study design, data collection and analysis, decision to publish, and preparation of the manuscript.