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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.

Targeting CD137 Enhances Vaccine-Elicited Anti–Respiratory Syncytial Virus CD8+ T Cell Responses in Aged Mice