Immune Memory and Immune Response in Children From Bulgaria 5–15 Years After Primary Hepatitis B Vaccination

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Bulgaria adopted the World Health Organization recommendation of routine universal infant vaccination against hepatitis B in 1991. Nevertheless, only a few studies evaluated the protection after the vaccination against hepatitis B, especially in children. The objective of this study was to investigate the duration of protection against hepatitis B in children aged 5–15 years after primary immunization, by measuring the immune and anamnestic immune response and possible breakthrough infections.


A total of 141 children (aged 5–17 years) were recruited randomly and divided into 3 groups, approximately 5 years (group 1), 10 years (group 2) and 15 years (group 3) after primary immunization with a recombinant hepatitis B vaccine; they were tested for hepatitis B markers: hepatitis B surface antigen anti-hepatitis core antibody and antibodies to hepatitis B surface antigen (anti-HB). A booster dose of vaccine was administered to 23 children with titers of anti-HBs antibodies below the threshold considered to be protective (<10 mIU/mL). Anti-HBs concentrations and geometric mean concentration (GMC) were determined before and 21–28 days after the booster vaccination.


Protective anti-HBs antibodies were detected in 95 of 141 (67.4 %) tested children, with a GMC of 63.57 mIU/mL. The seroprotection rate and GMC by groups was respectively: 84.6% and GMC of 76.05 mIU/mL in group 1; 55.8% and GMC of 58.1 mIU/mL in group 2; and 61.1% and GMC of 50.33 mIU/mL in group 3. Hepatitis B surface antigen and anti-hepatitis core antibody were found in 1 of the 141 subjects (0.7%). Of the remaining 140 children, 95 had anti-HBs ≥10 mIU/mL, and anti-hepatitis core antibodies were not detected. A booster dose of hepatitis B vaccine was administered to 23 of 45 (51%) children with anti-HBs <10 mIU/mL. Anamnestic immune response was shown in 100% of the children: the GMC was 337.38 mIU/mL and protective antibodies ranged between 15 and 955 mIU/mL.


The study demonstrates the presence of immune memory and protection 5–15 years after the initial course of newborn immunization with recombinant vaccines against hepatitis B.

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