title: Lung homing CTLs and their proliferation ability are important correlates of vaccine protection against influenza.
abstract: We conducted a study to evaluate the protective efficacy in mice of vaccination with novel adenovirus vectors expressing an influenza A nucleoprotein (AdFluA-NP) based on isolates from non-human primates. In a previous study, we had observed that AdFluA-NP vectors can induce similar T cell responses in mice yet differ in ability to protect animals from lethal challenge with influenza A virus. To better define correlates of protection, we extended our study design to include additional novel AdFluA-NP vectors, and to evaluate cytotoxic T lymphocyte (CTL) responses in the spleens and lungs of immunized mice prior to virus challenge. As in our previous study, all vectors induced similar numbers of antigen-specific interferon gamma (IFNgamma) secreting T cells and memory T cells in the spleen 4 weeks post immunization, but differed in their ability to protect the animals from lethal infection. However, cytokine-secreting NP antigen-specific CTLs in the lungs of mice from immunization groups that survived lethal challenge showed greater proliferative ability and higher CD27 expression. In addition, NP antigen-specific peripheral blood lymphocytes from protected mice showed greater proliferative ability after ex vivo stimulation. Our results provide additional correlates of protection that should be considered when developing anti-influenza vaccines.
authors.affiliation: Gene Therapy Program, Department of Pathology and Laboratory Medicine, Division of Transfusion Medicine, University of Pennsylvania, TRL Suite 2000, 125 South 31st Street, Philadelphia, PA 19104-4268, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Lin
authors.forename: Suryanarayan
authors.initials: S
authors.lastname: Somanathan
authors.forename: Soumitra
authors.initials: S
authors.lastname: Roy
authors.forename: Roberto
authors.initials: R
authors.lastname: Calcedo
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D016601:RNA-Binding Proteins / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D014758:Viral Core Proteins / Q000276:immunology*
chemical_list: D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014758:Viral Core Proteins