title: Targeting CD137 enhances vaccine-elicited anti-respiratory syncytial virus CD8+ T cell responses in aged mice.
abstract: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children and the elderly. No vaccines for RSV are in use. Because of immunosenescence, the immunologic requirements for a successful RSV vaccine in the elderly might differ from a RSV vaccine for young children. Using an aged mouse model of RSV pathogenesis, we found that aged mice had impaired Ag-specific CD8(+) T cell responses and delayed RSV clearance compared with young mice. To study vaccine-elicited RSV-specific CD8(+) T cells in aged mice, we used a peptide vaccine approach. TriVax is a commixture of a peptide representing immunodominant RSV CD8(+) T cell epitope M282-90, a TLR agonist (polyinosinic-polycytidylic acid), and a costimulatory anti-CD40 Ab. TriVax vaccination generated robust, polyfunctional, and protective CD8(+) T cell responses in young BALB/c mice, but not in 18-mo-old (aged) BALB/c mice. We hypothesized that treatment of aged mice with agonistic anti-CD137 (41BB) mAb will partially restore T cell responses and TriVax efficacy in aged mice. We immunized 18-mo-old BALB/c mice twice with TriVax + anti-41BB mAb or TriVax + isotype control Ab. Coadministration of anti-41BB mAb with TriVax enhanced RSV-specific CD8(+) T cell responses and TriVax efficacy in challenge experiments. Triggering the 41BB costimulatory pathway may be a strategy for enhancing T cell responses to vaccines in the elderly.
authors.affiliation: Department of Pediatrics, Emory University, Atlanta, GA 30322;
authors.forename: Sujin
authors.initials: S
authors.lastname: Lee
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mittler
authors.forename: Martin L
authors.initials: ML
authors.lastname: Moore
mesh_terms: D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051379:Mice; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000819:agonists / Q000276:immunology*; D014611:Vaccination
chemical_list: D000911:Antibodies, Monoclonal; D022261:Respiratory Syncytial Virus Vaccines; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D007371:Interferon-gamma