Three-dose versus four-dose primary schedules for tick-borne encephalitis (TBE) vaccine FSME-immun for those aged 50 years or older: A single-centre, open-label, randomized controlled trial.

• TBE vaccination failures among those aged 50+ suggest declining immune response. • We studied the immunogenicity of the TBE vaccine FSME-Immun in various age groups. • Immune response to FSME-Immun declined with age. • We compared the immunogenicity of a three- and two different four-dose regimens. • For those aged 50+, the accelerated 0–7–21–360 regimen appeared most immunogenic. TBE vaccination failures among those past middle age have raised concern about immune response declining with age. We investigated immunogenicity of the TBE-vaccine FSME-Immun among those aged 50+ years using the standard three-dose primary series and alternative four-dose schedules. In this single-centre, open-label, randomized controlled trial, 200 TBE-naive Swedish adults were given primary TBE vaccination with FSME-Immun. Those aged 50+ years (n = 150) were randomized to receive the standard three-dose (days 0–30–360) or one of two four-dose series (0–7–21–360; 0–30–90–360). For participants < 50 years (n = 50) the standard three-dose schedule was used. Titres of neutralizing antibodies were determined on days 0, 60, 120, 360, and 400. The main outcome was the log titre of TBE virus-specific neutralizing antibodies on day 400. The three-dose schedule yielded lower antibody titres among those aged 50+ years than the younger participants on day 400 (geometric mean titre 41 versus 74, p < 0.05). The older group showed higher titres for the four-dose 0–7–21–360 than the standard three-dose schedule both on day 400 (103 versus 41, p < 0.01; primary end point) and at the other testing points (days 60, 120, 360). Using the other four-dose schedule (0–30–90–360), no such difference was observed on day 400 (63 versus 41, NS). Immune response to the TBE vaccine declined with age. A four-dose schedule (0–7–21–360) may benefit those aged 50 years or older. This study is registered at ClinicalTrials.gov, NCT01361776. [ABSTRACT FROM AUTHOR]