title: Influenza-pseudotyped Gag virus-like particle vaccines provide broad protection against highly pathogenic avian influenza challenge.
abstract: Influenza-pseudotyped Gag virus-like particles (VLPs) were produced via the expression of influenza hemagglutinin (HA), neuraminidase (NA) and the murine leukemia virus Gag product in the baculovirus-insect cell expression system. Hemagglutination specific activities of sucrose gradient-purified VLPs were similar to those of egg-grown influenza viruses but particle morphologies were gamma retrovirus-like in the form of consistent 100nm spheres. Immunization of mice and ferrets demonstrated robust immunogenicity and protection from challenge with no measurable morbidity. Ferret data were striking in that immunization with H5N1 VLPs representing either A/Vietnam/1203/04 or A/Indonesia/5/05 resulted in solid protection against highly pathogenic A/Vietnam/1203/04 challenge with no detectable virus in the upper respiratory tract post-challenge in either group. H1N1 VLP immunization of ferrets resulted in partial protection against H5N1 challenge with markedly accelerated virus clearance from the upper respiratory tract relative to controls. The immunogenicity of influenza-pseudotyped VLPs was not dependent on the adjuvant properties of replication competent contaminating baculovirus. These data demonstrate robust vaccine protection of Gag-based, influenza-pseudotyped VLPs carrying a variety of influenza antigens and suggest applicability toward a number of additional respiratory viruses.
authors.affiliation: LigoCyte Pharmaceuticals, Inc. 2155 Analysis Dr., Bozeman, MT 59718, USA. joel.haynes@ligocyte.com
authors.forename: Joel R
authors.initials: JR
authors.lastname: Haynes
authors.forename: Leslie
authors.initials: L
authors.lastname: Dokken
authors.forename: James A
authors.initials: JA
authors.lastname: Wiley
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Cawthon
authors.forename: John
authors.initials: J
authors.lastname: Bigger
authors.forename: Allen G
authors.initials: AG
authors.lastname: Harmsen
authors.forename: Charles
authors.initials: C
authors.lastname: Richardson
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005289:Ferrets / Q000276:immunology; D015683:Gene Products, gag / Q000008:administration & dosage / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology / Q000302:isolation & purification; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D013997:Time Factors; D014771:Virion / Q000276:immunology*
chemical_list: D015683:Gene Products, gag; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D009439:Neuraminidase