title: Pseudotyped influenza A virus as a vaccine for the induction of heterotypic immunity.
abstract: There is a need for vaccines that can protect broadly across all influenza A strains. We have produced a pseudotyped influenza virus based on suppression of the A/PR/8/34 hemagglutinin signal sequence (S-FLU) that can infect cells and express the viral core proteins and neuraminidase but cannot replicate. We show that when given by inhalation to mice, S-FLU is nonpathogenic but generates a vigorous T cell response in the lung associated with markedly reduced viral titers and weight loss after challenge with H1 and H3 influenza viruses. These properties of S-FLU suggest that it may have potential as a broadly protective A virus vaccine, particularly in the setting of a threatened pandemic before matched subunit vaccines become available.
authors.affiliation: Molecular Immunology Group, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Powell
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Silk
authors.forename: Jane
authors.initials: J
authors.lastname: Sharps
authors.forename: Ervin
authors.initials: E
authors.lastname: Fodor
authors.forename: Alain R M
authors.initials: AR
authors.lastname: Townsend
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines