Treatment with Anti-CD137 (41BB) mAb enhances peptide vaccination against respiratory syncytial virus in aged mice (106.2)

Abstract

Abstract Respiratory syncytial virus (RSV) is the most important pathogen for lower respiratory tract illness (LRI) in infants and also a major cause of morbidity and mortality in the elderly. Using an aged mouse model of RSV pathogenesis, we found that aged mice had impaired antigen-specific CD8 T cell responses and delayed RSV clearance compared to young mice. We generated a peptide vaccine approach, TriVax, which is a co-mixture of a peptide representing an immunodominant RSV CD8 T cell epitope, a Toll-like receptor agonist, and a costimulatory anti-CD40 antibody. TriVax vaccination generated robust CD8 T cell responses and had a protective effect against RSV challenge in young BALB/c mice but not in aged BALB/c mice. We hypothesized that treatment of aged mice with agonistic CD137 (41BB) monoclonal antibody would stimulate T cells and enhance TriVax efficacy to RSV challenge in aged mice. We immunized 18-month old BALB/c mice twice with TriVax + anti-CD137 mAb. We found that co-administration of anti-CD137 mAb with TriVax enhanced antigen-specific CD8 T cell responses as well as showed a protective effect after RSV challenge. Thus, anti-CD137 mAb treatment rescued the deficient response to RSV TriVax vaccination in aged mice. The 41BB co-stimulatory pathway may be a target for enhancing T cell responses in the elderly.