BACKGROUND:Hepatitis B virus infection is a major health problem. Although non-response is known to increase with age, hepatitis B vaccinations are considered to have only minor non-response rates (anti-HBs<10IU/L) in healthy subjects. OBJECTIVES:The aim of this study was to quantify immunosenescence in a large retrospective cohort of 11,439 healthy adults who received HBV immunisation according to the standard vaccination regime. STUDY DESIGN:We evaluated the response to the standard three-dose vaccination regimen, consisting of 20-μg doses of the HbsAg recombinant DNA hepatitis B vaccine, among 11,439 healthy employees using a retrospective cohort design. Logistic regression was applied to predict the non-response rate, and multivariate regression analysis was applied to predict antibody response. Predictors of responsiveness included sex, age and time between the last vaccination and antibody titre measurement. RESULTS:From the age of 29 on in men and 43 on in women, more than 5% of subjects did not respond. Compared with women, men had a higher risk of non-response and exhibited a steeper decline in antibody titres produced with increasing age. CONCLUSIONS:This retrospective cohort study demonstrates that immunosenescence starts at young age, especially among men, underlining the importance of vaccination at a young age to achieve long-lasting immunity. Moreover, HBV vaccination should always include testing for antibodies to facilitate the performance of necessary interventions to prevent long-term fatal complications.