Immunogenicity and Protective Efficacy of a Vero Cell Culture-Derived Whole-Virus H7N9 Vaccine in Mice and Guinea Pigs

Walter Wodal,Richard Fritz,Anita Karner-Pichl,Michael G Schwendinger,M Keith Howard,Peter Brühl,Brian A Crowe,Helga Savidis-Dacho,Daniel Portsmouth,Otfried Kistner,Dalida Balta,Leopold Grillberger,Christine Hohenadl,P Noel Barrett,Stephen Mark Tompkins

doi:10.1371/journal.pone.0113963

Abstract

BackgroundA 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.MethodsAntibody 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.ResultsThe 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.ConclusionsThe 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.

Highlights

A novel influenza A/H7N9 virus emerged in February in China in 2013 [1,2,3] which infects humans and causes severe lower respiratory tract infections, with clinical symptoms including pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS) and multiorgan failure [1,4]
We evaluated the immunogenicity and protective efficacy of a candidate Vero cell culturederived whole-virus H7N9 vaccine in small animal models
The whole-virus H7N9 vaccine induced dose-dependent H7N9-specific hemagglutination inhibition (HI), MN and neuraminidase inhibition (NAi) antibodies in mice and guinea pigs

Summary

Introduction

A novel influenza A/H7N9 virus emerged in February in China in 2013 [1,2,3] which infects humans and causes severe lower respiratory tract infections, with clinical symptoms including pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS) and multiorgan failure [1,4]. H7N9 attaches to epithelium in both the upper and lower human respiratory tract, a pattern which has not previously been reported for any avian influenza virus [12]. Several H7N9 isolates were shown to contain amino acid changes which facilitate infection of mammals [13], and to contain a deletion in the NA stalk similar to an NA stalk deletion in H5N1 viruses which facilitates virus replication in the respiratory tract, and which might be associated with adaptation and transmission in domestic poultry [1]. 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 culturederived whole-virus H7N9 vaccine in small animal models

Methods

Discussion

Conclusion