More than half of the adolescents who received a 4-dose vaccination schedule in their infancy maintained seroprotective antibody levels against infection from hepatitis B virus (HBV), according to a study published in the Human Vaccines & Immunotherapeutics. A robust anamnestic response was mounted in most participating adolescents when challenged with a dose of monovalent HBV vaccine.
This phase 4, open-label study (ClinicalTrials.gov Identifier: NCT02798952) sought to evaluate antibody persistence against HBV in adolescents who were previously vaccinated as newborns with hexavalent diphtheria-tetanus-acellular pertussis-HBV-inactivated poliovirus-Haemophilus influenza type b conjugate vaccine (DTPa-HBV-IPV/Hib). The study investigators assessed the ability of each participant to mount an anamnestic response to a single challenge dose of monovalent HBV vaccine, along with the challenge dose’s reactogenicity and safety.
The study included 302 adolescent patients aged 14 to 15 years who were part of the national newborn immunization program in Germany. Participants had been primed in their infancy with 3 doses of DTPa-HBV-IPV/Hib given at 2, 3, and 4 months of age, and a booster dose at 11 to 14 months of age. Antibody levels against hepatitis B surface antigen (HBs) were determined in blood samples taken before the challenge vaccination and 1-month post vaccination.
A total of 268 participants were included in the according-to-protocol cohort for immunogenicity. Prior to taking the challenge dose, 53.7% of this cohort was considered seroprotected with anti-HBs antibody concentrations ≥10 mIU/mL.
In seronegative participants with <10 mIU/mL anti-HBs antibody concentrations, 82.9% achieved concentrations ≥10 mIU/mL after receiving the challenge vaccination. In fact, a strong anamnestic response was mounted in 92.5% of all study participants; the overall geometric mean concentration of anti-HBs antibodies increased 126.6 times from pre-vaccination levels.
In post challenge dose follow-up, 65.5% of the participating adolescents reported at least 1 solicited or unsolicited adverse event. The most frequently reported solicited symptoms were injection site pain (33.6%) and fatigue (30.2%).
Of the 55 total unsolicited adverse events reported, only 6 were considered casually related to the vaccination: 2 participants reported dizziness and 1 each reported injection site pruritus, malaise, pain, and pain in an extremity. Two serious adverse events were reported during the study, a meniscus injury and an eating disorder, but were considered unrelated to the vaccination.
Limitations of the study included an open label, non-randomized design that was only conducted in 1 country. Study investigators did not evaluate the cell-mediated immune response, which may not diminish with antibody levels, revealing a potential limitation. Finally, a lack of data from post-primary and post-booster immune responses in infancy prevented the investigators from identifying early non-responders.
Long-term antibody persistence against HBV was observed in more than half of adolescents previously primed in infancy with 4 doses of DTPa-HBV-IPV/Hib. A challenge dose of monovalent HBV vaccine induced a strong immune response even in most seronegative participants and was considered safe and well tolerated for patients aged 14 to 15 years.
Disclosures: This study was sponsored by GlaxoSmithKline Biologicals SA. Please refer to reference text for full list of authors’ disclosures.
Schwarz TF, Behre U, Adelt T, et al. Long-term antibody persistence against hepatitis B in adolescents 14–15-years of age vaccinated with 4 doses of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy [published online August 17, 2018]. Hum Vaccin Immunother. doi: 10.1080/21645515.2018.1509658