title: Differential activities of alpha/beta IFN subtypes against influenza virus in vivo and enhancement of specific immune responses in DNA vaccinated mice expressing haemagglutinin and nucleoprotein.
abstract: Vaccines are urgently needed to elicit immunity to different influenza virus strains. DNA vaccines can elicit partial protective immunity, however their efficacy requires improvement. We assessed the capacity of individual type I IFN multigene family members as subtype transgenes to abrogate influenza virus replication in a vaccination/challenge mouse model. Differences in antiviral efficacy were found among the subtypes with IFNA5 and IFNA6 being most effective, while IFNA1 was the least effective in reducing lung virus replication. Mice vaccinated with combinatorial HA/IFNA6 or NP/IFNA6 showed reduced lung viral titres, clinical score, body weight loss, and pulmonary tissue damage compared to IFNA6, HA, or NP viral vaccination alone. In addition, IFNA6 increased IgG2a titres with upregulation of IFN-gamma response in the respiratory tract. We conclude that IFN-alpha 6 has antiviral and immunomodulatory effects, which improve efficacy of DNA vaccines for enhanced control of influenza.
authors.affiliation: School of Veterinary and Biomedical Sciences, Division of Health Sciences, Murdoch University, South Street, Perth, Western Australia 6150, Australia. casjames@murdoch.edu.au
authors.forename: Cassandra M
authors.initials: CM
authors.lastname: James
authors.forename: Mohammad Y
authors.initials: MY
authors.lastname: Abdad
authors.forename: Josephine P
authors.initials: JP
authors.lastname: Mansfield
authors.forename: Hege K
authors.initials: HK
authors.lastname: Jacobsen
authors.forename: Azita Rezazadeh
authors.initials: AR
authors.lastname: Vind
authors.forename: Philip A
authors.initials: PA
authors.lastname: Stumbles
authors.forename: Emmalene J
authors.initials: EJ
authors.lastname: Bartlett
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001835:Body Weight; D004195:Disease Models, Animal; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D016898:Interferon-alpha / Q000145:classification / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D016898:Interferon-alpha; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D007371:Interferon-gamma