Immune cell telomerase activity may impact vaccine response in the elderly. Fifty persons aged 60-100 years were tested for post-influenza vaccination telomerase RNA expression (TERT) in peripheral blood mononuclear cells to assess for an association with influenza antibody levels and influenza-like illness or incident respiratory infection (IRI) in the year following vaccination. High rates of seroprotective influenza antibody (> or = 1:40 titers) were observed post-vaccination (86-92% to vaccine viral strains), with no association to TERT. No IRI occurred among persons in the top quartile of TERT expression, whereas the IRI rate was 33% in the lower three quartiles (Kaplan-Meier P=0.028). TERT expression was also IRI significantly higher in those who did not experience IRI than those who did in the follow-up period (0.845 vs. 0.301, P=0.024). These data suggest that telomerase expression may correlate with immune capacity for vaccine response in the elderly and could represent a target for recognizing risk for vaccine failure.