title: Intranasal vaccination with H5, H7 and H9 hemagglutinins co-localized in a virus-like particle protects ferrets from multiple avian influenza viruses.
abstract: Avian influenza H5, H7 and H9 viruses top the World Health Organization's (WHO) list of subtypes with the greatest pandemic potential. Here we describe a recombinant virus-like particle (VLP) that co-localizes hemagglutinin (HA) proteins derived from H5N1, H7N2, and H9N2 viruses as an experimental vaccine against these viruses. A baculovirus vector was configured to co-express the H5, H7, and H9 genes from A/Viet Nam/1203/2004 (H5N1), A/New York/107/2003 (H7N2) and A/Hong Kong/33982/2009 (H9N2) viruses, respectively, as well as neuraminidase (NA) and matrix (M1) genes from A/Puerto Rico/8/1934 (H1N1) virus. Co-expression of these genes in Sf9 cells resulted in production of triple-subtype VLPs containing HA molecules derived from the three influenza viruses. The triple-subtype VLPs exhibited hemagglutination and neuraminidase activities and morphologically resembled influenza virions. Intranasal vaccination of ferrets with the VLPs resulted in induction of serum antibody responses and efficient protection against experimental challenges with H5N1, H7N2, and H9N2 viruses.
authors.affiliation: Medigen, Inc, 4539 Metropolitan Court, Frederick, MD, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Tretyakova
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Pearce
authors.forename: Ruth
authors.initials: R
authors.lastname: Florese
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
authors.forename: Peter
authors.initials: P
authors.lastname: Pushko
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology / Q000472:pathogenicity; D057917:Influenza A Virus, H7N2 Subtype / Q000276:immunology / Q000472:pathogenicity; D053127:Influenza A Virus, H9N2 Subtype / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary* / Q000821:virology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014611:Vaccination / Q000662:veterinary*; D014771:Virion / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins