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Determinants of Long-term Protection After Hepatitis B Vaccination in Infancy: A Meta-analysis

Schönberger, Katharina MSc, MPH*; Riedel, Christina MSc*; Rückinger, Simon PhD*; Mansmann, Ulrich MSc; Jilg, Wolfgang MD; Kries, Rüdiger v. MD, MPH*

The Pediatric Infectious Disease Journal: April 2013 - Volume 32 - Issue 4 - p 307–313
doi: 10.1097/INF.0b013e31827bd1b0
Original Studies

Background: The duration of protection after hepatitis B vaccination in early infancy is unclear and may be related to vaccination schedule, dosage, vaccine type and population characteristics. Factors potentially influencing waning immunity were assessed.

Methods: A systematic review was performed. The main outcomes were prevalence of anti-hepatits B antibodies ≥ 10 mIU/mL after primary or booster vaccination. Factors potentially influencing protection were assessed in an adjusted random-effects meta-analysis model by age for both outcomes. Results of both meta-analyses were combined in a prognostic model.

Results: Forty-six studies reporting on the anti-hepatits B antibodies ≥ 10 mIU/mL 5 to 20 years after primary immunization and 29 on booster response were identified. The adjusted meta-analyses identified maternal carrier status (odds ratio [OR]: 2.37 [1.11; 5.08]), lower vaccine dosage than presently recommended (OR: 0.14 [0.06; 0.30]) and gap time between last and preceding dose of the primary vaccine series (OR: 0.44 [0.22; 0.86]) as determinants for persistence of anti-hepatits B antibodies ≥ 10. A lower vaccine dosage was also associated with failure to respond to booster (OR: 0.20 [0.10; 0.38]). The prognostic model predicted long-term protection of 90% [77%; 100%] at the age of 17 years for offspring of noncarrier mothers vaccinated with a presently recommended dose and vaccination schedule.

Conclusions: Based on meta-analyses, predictors of waning immunity after hepatitis B vaccination in infancy could be identified. A prognostic model for long-term protection after hepatitis B vaccination in infancy was developed.

Supplemental Digital Content is available in the text.

From the *Institute of Social Pediatrics and Adolescent Medicine, Division of Epidemiology; Department of Medical Informatics, Biostatistics and Epidemiology, Ludwig Maximilians University of Munich, Munich; and Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.

Accepted for publication October 30, 2012.

The project was funded by Robert Koch-Institute grant 1362/1–925. The grant donating agency had no influence on the design or conduct of this study. Prof. Wolfgang Jilg has received honoraria for lectures from GlaxoSmithKline and SanofiPasteur-MSD and served as principal investigator in a clinical trial on hepatitis B vaccination sponsored by GlaxoSmithKline. The authors have no other funding or conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Address for correspondence: Katharina Schönberger, MSc, MPH, Institute of Social Pediatrics and Adolescent Medicine, Division of Epidemiology, Ludwig Maximilians University of Munich, Heiglhofstr. 63, 81377 München, Germany. E-mail:

© 2013 Lippincott Williams & Wilkins, Inc.