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Hepatitis B immune memory in children primed with hexavalent vaccines and given monovalent booster vaccines: an
Alessandro Remo Zanetti1, Luisa Romanò, Cristina Giambi
1Department of Public Health-Microbiology-Virology, University of Milan, Milan, Italy. alessandro.zanetti@unimi.it
Insights
Five years after primary immunization, children vaccinated with Hexavac showed lower antibody levels against Hepatitis B compared to Infanrix Hexa. However, immunological memory persisted, suggesting booster doses may not be necessary.
Area of Science:
- Pediatric Immunology
- Vaccinology
- Public Health
Background:
- Hexavac and Infanrix Hexa vaccines were licensed in Europe in 2000 for primary immunization.
- Hexavac was suspended in 2005 due to concerns regarding long-term immunogenicity of its hepatitis B component.
- This study assessed the duration of immunity and need for booster injections in children vaccinated with these hexavalent vaccines.
Purpose of the Study:
- To evaluate the duration of immunity provided by Hexavac and Infanrix Hexa vaccines.
- To determine the need for booster injections in children primed with these vaccines.
- To compare antibody concentrations and immunological memory 5 years post-vaccination.
Main Methods:
- An open-label, randomized, controlled, multicenter study was conducted.
- Antibody concentrations (anti-HBs) were measured 5 years after primary immunization.
- Children with anti-HBs < 10 mIU/mL received a booster vaccine and were re-tested after 2 weeks.
Main Results:
- Only 38.4% of children who received Hexavac maintained anti-HBs ≥ 10 mIU/mL at 5 years, compared to 83.2% for Infanrix Hexa (p<0.0001).
- Geometric mean concentrations (GMCs) were significantly lower in the Hexavac group (4.5 mIU/mL) versus the Infanrix Hexa group (61.3 mIU/mL).
- Following a booster dose, both groups showed robust anamnestic responses, with over 92% achieving anti-HBs ≥ 10 mIU/mL.
Conclusions:
- Despite lower initial antibody levels, immunological memory persists in children vaccinated with Hexavac.
- Booster doses for Hepatitis B may not be necessary for children primed with Hexavac, even with low antibody concentrations 5 years post-vaccination.
- Further follow-up is recommended to confirm long-term immunity.
Background:
In 2000, hexavac and infanrix hexa were licensed in Europe for primary immunisation of children against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, and invasive infections caused by Haemophilus influenzae b. In 2005, hexavac was suspended because of concerns about the long-term immunogenicity of its hepatitis B component. We aimed to assess the duration of immunity and need for booster injections in children primed with these vaccines.
Methods:
In an open-label, randomised, controlled, multicentre study in six local health units and at the Bambino Gesù Paediatric Research Hospital in Italy, antibody concentrations were measured 5 years after immunisation of infants with hexavac or infanrix hexa. Children with concentrations of antibodies to hepatitis B surface antigen (anti-HBs) lower than 10 mIU/mL were randomly assigned by simple randomisation to receive a booster of HBVaxPro or engerix B monovalent hepatitis B vaccine and tested 2 weeks later. Primary endpoints were the proportion of children with anti-HBs concentrations of at least 10 mIU/mL, geometric mean concentrations (GMCs) of antibody 5 years after vaccination, and the proportion of children with anti-HBs concentrations lower than 10 mIU/mL who had anamnestic response to booster. The study is registered with Agenzia Italiana del Farmaco, code FARM67NFPN.
Findings:
1543 children were enrolled, 833 had received hexavac and 710 infanrix hexa. 831 children who received hexavac and 709 who received infanrix hexa were included in the analysis. 319 children who received hexavac (38.4%, 95% CI 35.1-41.7) had anti-HBs concentrations of at least 10 mIU/mL compared with 590 who received infanrix hexa (83.2%, 80.5-86.0; p<0.0001). GMCs before booster were 4.5 mIU/mL in the hexavac group compared with 61.3 mIU/mL in the infanrix hexa group (p<0.0001). After booster 409 (92.1%, 89.6-94.6) of 444 children primed with hexavac and 99 (94.3%, 89.8-98.7) of 105 primed with infanrix hexa had anti-HBs concentrations of at least 10 mIU/mL (p=0.4); GMCs were 448.7 mIU/mL and 484.9 mIU/mL (p=0·6). The two booster vaccine groups did not differ in number of side-effects; no serious adverse events were reported.
Interpretation:
5 years after immunisation with hexavalent vaccines, immunological memory seems to persist in children with anti-HBs concentrations lower than 10 mIU/mL, suggesting that booster doses are not needed. Additional follow-up is needed.
Funding:
Agenzia Italiana del Farmaco.
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