title: PB1 as a potential target for increasing the breadth of T-cell mediated immunity to Influenza A.
abstract: Recently, we showed that combined intranasal and subcutaneous immunization with a non-replicating adenoviral vector expressing NP of influenza A, strain PR8, induced long-standing protection against a range of influenza A viruses. However, H-2bmice challenged with an influenza A strain mutated in the dominant NP366epitope were not efficiently protected. To address this problem, we envision the use of a cocktail of adenovectors targeting different internal proteins of influenza A virus. Consequently, we investigated the possibility of using PB1 as a target for an adenovector-based vaccine against influenza A. Our results showed that PB1 is not as immunogenic as the NP protein. However, by tethering PB1 to the murine invariant chain we were able to circumvent this problem and raise quite high numbers of PB1-specific CD8+T cells in the circulation. Nevertheless, mice immunized against PB1 were not as efficiently protected against influenza A challenge as similarly NP-vaccinated animals. The reason for this is not a difference in the quality of the primed cells, nor in functional avidity. However, under similar conditions of immunization fewer PB1-specific cells were recruited to the airways, and surface expression of the dominant PB1 peptide, PB1703, was less stable than in the case of NP366.
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ida E M
authors.initials: IE
authors.lastname: Uddbäck
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Steffensen
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Pedersen
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Loulieta
authors.initials: L
authors.lastname: Nazerai
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan R
authors.initials: AR
authors.lastname: Thomsen
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Christensen
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D000229:Dependovirus / Q000235:genetics / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D051379:Mice; D009154:Mutation; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1; C045084:invariant chain