title: Incorporation of 4-1BB ligand into an adenovirus vaccine vector increases the number of functional antigen-specific CD8 T cells and enhances the duration of protection against influenza-induced respiratory disease.
abstract: T cell based influenza vaccines offer the potential for cross protective immunity to multiple clades of influenza virus. Here we explored the effect of increasing CD8 T cell responses during intranasal vaccination by incorporating a T cell costimulator, 4-1BBL. Inclusion of 4-1BBL in an influenza nucleoprotein (NP)-containing adenoviral vector increased the number of NP-specific CD8 T cells and lowered the vaccine dose required for short-term protection from influenza-induced disease in mice. At higher vaccine doses, the inclusion of 4-1BBL increased the duration of protection of mice from influenza-induced mortality. Bone marrow chimera experiments revealed that the major effects of 4-1BBL were directly on αβ T cells with minor additional effects through cells other than αβ T cells. The implications of these findings are that including 4-1BBL or adjuvants that induce 4-1BBL expression may be of benefit in a vaccine setting for enhancing the magnitude and duration of T cell responses to influenza virus.
authors.affiliation: The Department of Immunology, University of Toronto, Toronto, Ontario, Canada, M5S 1A8.
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Moraes
authors.forename: Gloria H Y
authors.initials: GH
authors.lastname: Lin
authors.forename: Tao
authors.initials: T
authors.lastname: Wen
authors.forename: Tania H
authors.initials: TH
authors.lastname: Watts
mesh_terms: D053330:4-1BB Ligand / Q000276:immunology*; D000256:Adenoviridae / Q000276:immunology; D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D056738:Cross Protection; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009698:Nucleoproteins / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D012140:Respiratory Tract Diseases / Q000276:immunology / Q000517:prevention & control*; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D053330:4-1BB Ligand; D007252:Influenza Vaccines; D009698:Nucleoproteins; D014765:Viral Vaccines