Markers of Protection in Children and Adolescents Six to Fourteen Years After Primary Hepatitis B Vaccination in Real Life

A Pilot Study

Irena Brunskole Hummel, PhD; Barbara Huber, PhD; Jürgen J. Wenzel, MD; Wolfgang Jilg, MD


Pediatr Infect Dis J. 2016;35(3):286-291. 

In This Article

Abstract and Introduction


Background: Not many data are available on long-term immunity against hepatitis B (HB) for children vaccinated under real-life conditions.

Methods: Two hundred and thirty-two children and adolescents vaccinated 6–14 years earlier in pediatric practices were examined for conditions of vaccination and markers of protection as anti-HBs, anamnestic response to a booster dose and cell-mediated immunity.

Results: Fifty-six percent of the participants were vaccinated according to the German vaccination recommendations (group 1). In 44.0% (group 2), these recommendations were not followed. Anti-HBs concentrations of ≥10 IU/L were found in 53.1% of group 1 and 45.1% of group 2 participants. A booster dose resulted in 91 of 99 participants in having an anamnestic response, in 3 (5.9%) of group 1 and 5 (10.4%) of group 2 anti-HBs remained below 10 IU/L. In group 1, postbooster anti-HBs concentration was inversely correlated with time since the last vaccination. Cellular immune responses were seen in only 5% of revaccinated individuals before the booster, increasing to 30% thereafter.

Conclusions: Under real-life conditions about half of vaccinees have lost protecting antibodies 6–14 years after vaccination in infancy, but in approximately 90% of them, immune memory was demonstrated. However, as memory may wane, revaccination at a time when boostability is still present might be considered.


Persistence of immunity after hepatitis B (HB) vaccination in infancy is still a matter of debate. It has been convincingly shown in the past that the vaccine induces not only protection against infection but also protection against disease when neutralizing antibodies have disappeared. Therefore, it is assumed that immunity is long-lived, and booster doses are not necessary in immunologically competent individuals after a full vaccination course.[1–3] However, results of a recent meta-analysis suggest waning of immune memory 15–20 years after primary vaccination in about one third of individuals whose anti-HBs level has fallen below the protecting level of 10 IU/L, which questions their further protection also against disease.[4] Thus, the question whether a booster dose might be necessary is still not answered. If a booster should be given it would be wise to do so in early adolescence to maintain or reestablish reliable protection for the lifespan where it is needed most. According to several studies the ability to mount an anamnestic response when anti-HBs has fallen below 10 IU/L is still present in early adolescence, that is, about 10–12 years after the primary vaccination course.[5,6] However, in most of these studies infants were vaccinated under strict study conditions regarding vaccines used and timing of doses, or were retrospectively selected according to these criteria. Under real-life conditions, it is very likely that for several reasons not all pediatricians or family doctors strictly adhere to the recommendations of their local health authorities or the producers of the vaccine, which means that a number of infants are vaccinated using somewhat irregular schedules. How this influences long-term immunity is not known. To shed light on this question, we examined children and adolescents vaccinated 6–14 years earlier in different pediatricians and family doctors practices. Our aim was to find out how children are vaccinated against HB under real-life conditions and to analyze them for markers of protection as anti-HBs, the ability to mount an anamnestic response when anti-HBs was below 10 IU/L, and for HB surface antigen (HBsAg)-specific cellular immunity.