title: Recombinant virus-like particles elicit protective immunity against avian influenza A(H7N9) virus infection in ferrets.
abstract: In March 2013, diagnosis of the first reported case of human infection with a novel avian-origin influenza A(H7N9) virus occurred in eastern China. Most human cases have resulted in severe respiratory illness and, in some instances, death. Currently there are no licensed vaccines against H7N9 virus, which continues to cause sporadic human infections. Recombinant virus-like particles (VLPs) have been previously shown to be safe and effective vaccines for influenza. In this study, we evaluated the immunogenicity and protective efficacy of a H7N9 VLP vaccine in the ferret challenge model. Purified recombinant H7N9 VLPs morphologically resembled influenza virions and elicited high-titer serum hemagglutination inhibition (HI) and neutralizing antibodies specific for A/Anhui/1/2013 (H7N9) virus. H7N9 VLP-immunized ferrets subsequently challenged with homologous virus displayed reductions in fever, weight loss, and virus shedding compared to these parameters in unimmunized control ferrets. H7N9 VLP was also effective in protecting against lung and tracheal infection. The addition of either ISCOMATRIX or Matrix-M1 adjuvant improved immunogenicity and protection of the VLP vaccine against H7N9 virus. These results provide support for the development of a safe and effective human VLP vaccine with potent adjuvants against avian influenza H7N9 virus with pandemic potential.
authors.affiliation: Novavax, Inc., 22 Firstfield, Gaithersburg, MD 20878, USA.
authors.forename: Ye V
authors.initials: YV
authors.lastname: Liu
authors.affiliation: Novavax, Inc., 22 Firstfield, Gaithersburg, MD 20878, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Massare
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Pearce
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Xiangjie
authors.initials: X
authors.lastname: Sun
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Belser
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Taronna R
authors.initials: TR
authors.lastname: Maines
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA; Microbiology and Molecular Genetics Graduate Program, Emory University, Atlanta, GA, USA.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Creager
authors.affiliation: Novavax, Inc., 22 Firstfield, Gaithersburg, MD 20878, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Glenn
authors.affiliation: Medigen, Inc., 8420 Gas House Pike, Frederick, MD, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Pushko
authors.affiliation: Novavax, Inc., 22 Firstfield, Gaithersburg, MD 20878, USA.
authors.forename: Gale E
authors.initials: GE
authors.lastname: Smith
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: tft9@cdc.gov.
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood*; D002681:China; D002784:Cholesterol / Q000276:immunology; D004195:Disease Models, Animal; D004338:Drug Combinations; D005289:Ferrets; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D010743:Phospholipids / Q000276:immunology; D012503:Saponins / Q000276:immunology; D014611:Vaccination; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000276:immunology*; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004338:Drug Combinations; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C493786:ISCOMATRIX; D007252:Influenza Vaccines; D010743:Phospholipids; D012503:Saponins; D058425:Vaccines, Virus-Like Particle; D002784:Cholesterol
keywords: Avian influenza; Ferret; Influenza; Vaccine; Virus