Because of decreased immune functions of older people booster intervals of 3 years – instead of 5 – are recommended for tick-borne encephalitis (TBE) vaccinations for persons ≥60 years in Austria. So far, no comparative data on the immune-responsiveness of the age group 50–59 years are available. We therefore investigated the antibody titers and booster responses (in ELISA and neutralization assays) for the age groups 50–59, 60–69, and >69 years in comparison to a control group below 30 years. The age group 50–59 years displayed the same decreased antibody response, also characteristic for persons 60 years and older. Although antibody concentrations were lower after 5–7 years compared to 3–4 year intervals, antibodies were still detectable and could be sufficiently increased by booster shots in the vast majority of persons. Our results clearly indicate that the responsiveness of the immune system to vaccination is already impaired at the age of 50.