title: Recombinant H7 hemagglutinin forms subviral particles that protect mice and ferrets from challenge with H7N9 influenza virus.
abstract: A novel avian-origin influenza A H7N9 virus emerged in China in 2013 and continues to cause sporadic human infections with mortality rates approaching 35%. Currently there are no approved human vaccines for H7N9 virus. Recombinant approaches including hemagglutinin (HA) and virus-like particles (VLPs) have resulted in experimental vaccines with advantageous safety and manufacturing characteristics. While high immunogenicity of VLP vaccines has been attributed to the native conformation of HA arranged in the regular repeated patterns within virus-like structures, there is limited data regarding molecular organization of HA within recombinant HA vaccine preparations. In this study, the full-length recombinant H7 protein (rH7) of A/Anhui/1/2013 (H7N9) virus was expressed in Sf9 cells. We showed that purified full-length rH7 retained functional ability to agglutinate red blood cells and formed oligomeric pleomorphic subviral particles (SVPs) of ∼20nm in diameter composed of approximately 10 HA0 molecules. No significant quantities of free monomeric HA0 were observed in rH7 preparation by size exclusion chromatography. Immunogenicity and protective efficacy of rH7 SVPs was confirmed in the mouse and ferret challenge models suggesting that SVPs can be used for vaccination against H7N9 virus.
authors.affiliation: Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD, USA. Electronic address: ppushko@medigen-usa.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Pushko
authors.affiliation: Viral Pathogenesis and Evolution Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, Bethesda, MD, USA.
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Pujanauski
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road N.E., Atlanta, GA, USA.
authors.forename: Xiangjie
authors.initials: X
authors.lastname: Sun
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road N.E., Atlanta, GA, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Pearce
authors.affiliation: Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD, USA.
authors.forename: Rachmat
authors.initials: R
authors.lastname: Hidajat
authors.affiliation: Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kort
authors.affiliation: Viral Pathogenesis and Evolution Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, Bethesda, MD, USA.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Schwartzman
authors.affiliation: Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Tretyakova
authors.affiliation: Wuhan Siqiyuan Ltd., 666 Gaoxin Road, Wuhan, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Chunqing
authors.affiliation: Viral Pathogenesis and Evolution Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, Bethesda, MD, USA.
authors.forename: Jeffery K
authors.initials: JK
authors.lastname: Taubenberger
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road N.E., Atlanta, GA, USA.
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D006384:Hemagglutination; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000276:immunology; D061987:Sf9 Cells; D018411:Spodoptera; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D058425:Vaccines, Virus-Like Particle; C109963:hemagglutinin, avian influenza A virus
keywords: H7N9; Influenza; Influenza vaccine; VLP; Virus-like particles