title: Characterization of a Bivalent Vaccine Capable of Inducing Protection Against Both Ebola and Cross-clade H5N1 Influenza in Mice.
abstract: BACKGROUND
  Ebola virus (EBOV) is a lethal pathogen that causes up to 90% mortality in humans, whereas H5N1 avian influenza has a 60% fatality rate. Both viruses are considered pandemic threats. The objective was to evaluate the protective efficacy of a bivalent, recombinant vesicular stomatitis virus vaccine expressing both the A/Hanoi/30408/2005 H5N1 hemagglutinin and the EBOV glycoprotein (VSVΔG-HA-ZGP) in a lethal mouse model of infection.
  
  
  METHODS
  Mice were vaccinated 28 days before or 30 minutes after a lethal challenge with mouse-adapted EBOV or selected H5N1 influenza viruses from clades 0, 1, and 2. Animals were monitored for weight loss and survival, in addition to humoral and cell-mediated responses after immunization.
  
  
  RESULTS
  A single VSVΔG-HA-ZGP injection was efficacious when administered 28 days before a homologous H5N1 and/or mouse-adapted EBOV challenge, as well as a heterologous H5N1 challenge. Postexposure protection was only observed in vaccinated animals challenged with homologous H5N1 and/or mouse-adapted EBOV. Analysis of the adaptive immune response postvaccination revealed robust specific T- and B-cell responses, including a potent hemagglutinin inhibition antibody response against all H5N1 strains tested.
  
  
  CONCLUSIONS
  The results highlight the ability of vesicular stomatitis virus-vectored vaccines to rapidly confer protection against 2 unrelated pathogens and stimulate cross-protection against H5N1 influenza viruses.
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, and Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Wong
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, and Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ebihara
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana.
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, and Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada Department of Immunology, University of Manitoba, Winnipeg, Canada Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002522:Chlorocebus aethiops; D056738:Cross Protection / Q000276:immunology*; D004285:Dogs; D029043:Ebolavirus / Q000276:immunology*; D005260:Female; D057809:HEK293 Cells; D006388:Hemagglutinins / Q000276:immunology; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D014709:Vero Cells; D018116:Vesiculovirus / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D006388:Hemagglutinins; D014765:Viral Vaccines
keywords: Ebola virus; H5N1 influenza virus; mice; vaccine; vesicular stomatitis virus