Immune memory to hepatitis B persists in children aged 7–8 years, who were vaccinated in infancy with 4 doses of hexavalent DTPa-HBV-IPV/Hib (<i>Infanrix™ hexa</i>) vaccine

We evaluated antibody persistence against hepatitis B virus (HBV) in adolescents previously vaccinated with a hexavalent diphtheria-tetanus-acellular pertussis-HBV-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPa-HBV-IPV/Hib), as part of the national newborn immunization program in Germany. We also assessed the anamnestic response to a challenge dose of a monovalent HBV vaccine. In this phase 4, open-label, non-randomized study (NCT02798952), 302 adolescents aged 14-15 years, primed in their first 2 years of life with 4 DTPa-HBV-IPV/Hib doses, received one challenge dose of monovalent HBV vaccine. Blood samples were taken before and one month post-vaccination and used to determine antibody levels against hepatitis B surface antigen (HBs). Reactogenicity and safety were also assessed post-challenge dose. Pre-challenge dose, 53.7% of 268 participants included in the according-to-protocol cohort for immunogenicity had anti-HBs antibody concentrations ≥10 mIU/mL (seroprotection cut-off) and 16.8% had anti-HBs antibody concentrations ≥100 mIU/mL. One month post-challenge dose, 93.3% of adolescents had anti-HBs antibody concentrations ≥10 mIU/mL and 87.3% had antibody concentrations ≥100 mIU/mL. An anamnestic response was mounted in 92.5% of adolescents. Injection site pain (in 33.6% of participants) and fatigue (30.2%) were the most frequently reported solicited local and general symptoms, respectively. Six of the 55 unsolicited adverse events reported were considered vaccination-related. Two vaccination-unrelated serious adverse events were reported during the study. Long-term antibody persistence against hepatitis B was observed in 14-15 years old adolescents previously primed in infancy with DTPa-HBV-IPV/Hib. A challenge dose of monovalent HBV vaccine induced strong anamnestic response, with no safety concerns.

Section: Introductionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 80%

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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

Schwarz

Behre

Adelt

et al. 2018

“…These data are consistent with previous studies that have shown the persistence of anti-HB T-cell and B-cell immune memory for decades following vaccination with HB-containing combination vaccines, even without regular booster vaccination. [26][27][28][29][30] As such, a strong anti-HBs response would be expected following subsequent HB exposure even in individuals with an anti-HBs antibody titer <10 mIU/mL, and the WHO have stated that 'the substantial body of evidence does not provide a compelling basis for recommending a booster dose of hepatitis B vaccine after completion of the primary vaccination series for persons with normal immune status'. 31 Overall, very good antibody persistence was demonstrated in two different vaccination schedules and in two different populations (South Africa and Latin America) with a variety of primary series/booster sequences, indicating that mixed primary series/ booster schedules are equally immunogenic as the administration of the same vaccine in a primary series and as a booster.…”

Section: Discussionmentioning

confidence: 99%

Antibody persistence in pre-school children after hexavalent vaccine infant primary and booster administration

Madhi

López

Zambrano

et al. 2019

Objective: Antibody persistence evaluation for all antigens of a fully liquid DTaP-IPV-HB-PRP~T vaccine at 3.5 and 4.5 y of age following different primary series and booster schedules in South Africa and Latin America. Methods: Participants had completed one of two previous studies (Study 1-South Africa; Study 2-Latin America). In Study 1, participants who had not received HB vaccine at birth received a 6-10-14 week primary series of DTaP-IPV-HB-PRP~T or DTwP/PRP~T-Hib+HB+OPV and a third group who had received HB vaccine at birth received a 6-10-14 week primary series of DTaP-IPV-HB-PRP~T; all received a booster (15-18 months) of the primary series vaccine(s) except for HB in the DTwP/PRP~T-Hib group. In Study 2, participants received HB vaccine at birth, a 2-4-6 month primary series of DTaP-IPV-HB-PRP~T or DTaP-HB-IPV//PRP~T, and a DTaP-IPV-HB-PRP~T or DTaP-HB-IPV//PRP~T booster (12-24 months). Participants were followed up at 3.5 and 4.5 y of age for antibody persistence.Results: Approximately 80% of eligible participants were assessed. In Study 1, a birth dose of HB increased anti-HBs persistence (≥10 mIU/mL) following DTaP-IPV-HB-PRP~T primary and booster vaccination from 76.3% to 96.1% at 3.5 y of age and from 73.3% to 96.1% at 4.5 y of age; in Study 2, anti-HBs persistence was high and similar in each group. For the other antigens, there were no differences between groups or studies at 3.5 or 4.5 y. Conclusion: Good persistence of antibodies to each antigen in the DTaP-IPV-HB-PRP~T vaccine up to pre-school age, irrespective of the vaccination schedule during the first 2 y of life. ARTICLE HISTORY

“…In order to assess long-term antibody persistence and immune memory against HBV, we set up a series of 4 studies with increasing follow-up times of children who received 4 doses of DTPa-HBV-IPV/Hib in routine clinical practice. The previous 2 studies assessed antibody persistence in children at 4–5 4 and 7–8 12 y of age and this third study evaluated adolescents aged 12–13 y.…”

Section: Introductionmentioning

confidence: 99%

Lasting immune memory against hepatitis B in 12–13-year-old adolescents previously vaccinated with 4 doses of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy

Behre

Meeren

Crasta

et al. 2016

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Background: Vaccinating infants against hepatitis B virus (HBV) is the most effective way of preventing the disease. However, since HBV exposure can increase during adolescence, it is essential that antibody persistence is maintained. We evaluated the antibody persistence and immune memory against hepatitis B, in 12-13 y olds who had received complete primary + booster vaccination with diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenza type b (DTPa-HBV-IPV/Hib) vaccine in infancy.Methods: Open phase-IV study conducted at 12 centers in Germany [NCT02052661]. Adolescents aged 12-13 y, vaccinated with 4 doses of DTPa-HBV-IPV/Hib (Infanrix hexa™, GSK Vaccines) in infancy, received a single challenge dose of monovalent pediatric hepatitis B vaccine (Engerix™-B Kinder; GSK Vaccines). Blood samples were taken before and 1-month post-challenge to measure anti-hepatitis B (anti-HBs) antibodies using a chemiluminescence immunoassay (seroprotection cut-off: ≥10 mIU/ml). Post-challenge adverse events (AEs) were monitored.Results: 300 subjects were vaccinated; of 293 subjects in the ATP immunogenicity cohort, 60.5% had pre-challenge anti-HBs antibodies ≥10 mIU/ml, which rose to 97.6% post-challenge (≥100 mIU/ml in 94.1%). An anamnestic response was seen in 96.5% subjects. A 150-fold increase in antibody geometric mean concentrations was observed (22.4 to 3502.6 mIU/ml). Pain (44%) and fatigue (24.3%) were the most frequent solicited local and general AEs, respectively; 14.7% subjects reported unsolicited symptoms during the 31-day post-vaccination period. Two vaccine-unrelated serious AEs occurred.Conclusion: Vaccination with DTPa-HBV-IPV/Hib in infancy induces sustained seroprotection and immune memory against HBV, as shown by the strong anamnestic response to the hepatitis B vaccine challenge in 12-13 year-old adolescents.