We have recently demonstrated that single shot vaccinations against tetanus and diphtheria do not lead to long-lasting immunity against diphtheria in elderly persons despite administration at 5?year intervals. against diphtheria before vaccination. 28?days after vaccination 100?% of all participants had protective antibody concentrations against tetanus and only a small percentage in each age group (<10?%) was unprotected against diphtheria. 5?years later 100 of both cohorts were still protected against tetanus but 24?% of the young and 54?% of the elderly group were unprotected against diphtheria. Antibody concentrations against diphtheria measured by ELISA correlated well with their neutralizing capacity. T cell responses to tetanus and diphtheria did not differ between young and old persons. We conclude that booster vaccinations against tetanus and diphtheria according to present recommendations provide long-lasting protection only against tetanus but not against diphtheria independently of age. In elderly persons the level of protection is even lower probably due to intrinsic age-related changes within the immune system and/or insufficient vaccination earlier in life. Electronic supplementary material WK23 The online version of this article (doi:10.1186/s12979-016-0081-0) contains supplementary material which is available to authorized WK23 users. <0.0001 rs >0.821 in both age groups at all time points Fig.?3). Fig 3 Diphtheria-specific Abs measured by ELISA and neutralizing assay. The concentrations of diphtheria-specific Abs measured by ELISA are shown in correlation to the highest plasma dilution factor able to neutralize diphtheria toxin (8?ng/ml). Diphtheria-specific … The impact of time since the last vaccination on Ab concentrations Recent vaccination history was synchronized for the older cohort as they had received tetanus and diphtheria vaccinations in the context of our studies in 2005 WK23 and 2010 [11 12 In contrast the time since the last vaccination before the recruitment in 2010 2010 varied considerably within the young group. Correlations between pre- and post-vaccination Ab concentrations in 2010 2010 and the time since the last vaccination were therefore only analyzed in the young group (Fig.?4). For tetanus there was no correlation between Ab concentrations and the time point of the last vaccination (Fig.?4a). In contrast for diphtheria there was a significant WK23 correlation between Ab concentrations and the time since the last vaccination (Fig.?4b). This correlation was most pronounced for the Ab concentrations 28?days after vaccination indicating that regular booster vaccinations against diphtheria are important not only for the maintenance of Ab levels but also for the success of booster vaccinations. Fig 4 Impact of vaccination history on Ab concentrations in young persons. Tetanus- a and diphtheria- b specific Ab concentrations are shown in correlation to the time since the last vaccination before recruitment for this study. Correlations were calculated … T cell responses to tetanus and diphtheria In a previously published study on elderly adults  we found a weak correlation between IL-5-producing T cells measured by Elispot and diphtheria-specific Abs. In the present study a detailed analysis of cytokine production by CD4+ memory cells was performed at the 2015 time point using flow cytometry. The production of 9 cytokines (IFN-γ TNF-α IL-2 IL-4 IL-10 IL-17 IL-21 TGF-β GM-CSF) following in vitro stimulation of PBMCs with tetanus WK23 (Fig.?5a and c) and diphtheria (Fig.?5b and d) toxoid was analyzed and was found to be similar in young (Fig.?5a and b) and elderly (Fig.?5c and d) adults. The production of more than one cytokine was detected in CD4+ BCL1 memory cells of all donors. Tetanus-specific T cells of young and old donors produced 5.8?±?1.2 (mean?± SD) and 5.4?±?1.8 cytokines respectively (n.s.; Wilcoxon rank-sum test). 4.2?±?1.0 and 4.0?±?1.4 cytokines were detected after stimulation with diphtheria toxoid in T cells of young and old donors respectively (n.s.; Wilcoxon rank-sum test). The frequency of all antigen-specific cytokine-producing T cells was similar in both age groups for tetanus and diphtheria (n.s.; Wilcoxon rank-sum test). Correlations between Ab concentrations and.