Prospective clinical trial of hepatitis B vaccination in adults with and without type-2 diabetes mellitus.

Objective: Patients with diabetes mellitus are at increased risk for hepatitis B virus (HBV) infection and its complications. HBV vaccination is recommended for adults with diabetes in the United States and other countries. However, few studies have assessed safety and immunogenicity of hepatitis B vaccine in such patients. We assessed the safety and immunogenicity of recombinant hepatitis B vaccine in subjects with and without diabetes mellitus. METHODS: Prospective, multi-country controlled study in 21 centers ( www.clinicaltrials.gov NCT01627340). Four hundred and sixteen participants with Type-2 diabetes and 258 controls matched for age and body mass index (BMI) (2:1 ratio) received 3-doses of HBV vaccine (Engerix-B™, GSK Vaccines, Belgium) according to a 0, 1, 6 months schedule. Antibodies were measured against HBV surface antigen and expressed as seroprotection rates (anti-HBs ≥10mIU/mL) and geometric mean concentration (GMC). RESULTS: The median age and BMI in patients with diabetes and controls (according-to-protocol cohort) were 54 y and 32.1 kg/m2, and 53 y and 30.8 kg/m2, respectively. Seroprotection rates (GMCs) one month post-dose-3 were 75.4% (147.6 mIU/mL) and 82.0% (384.2 mIU/mL) in patients with diabetes and controls, respectively. Age-stratified seroprotection rates for patients with diabetes were 88.5% (20-39 years), 81.2% (40-49 years), 83.2% (50-59 years), and 58.2% (≥60 years). The overall safety profile of hepatitis B vaccine was similar between groups. CONCLUSIONS: Hepatitis B vaccine is immunogenic in patients with diabetes and has a similar safety profile to vaccination in healthy controls. Because increasing age was generally associated with a reduction in seroprotection rates, hepatitis B vaccine should be administered as soon as possible after the diagnosis of diabetes.

Lasting immune memory against hepatitis B following challenge 10-11 years after primary vaccination with either three doses of hexavalent DTPa-HBV-IPV/Hib or monovalent hepatitis B vaccine at 3, 5 and 11-12 months of age.

BACKGROUND: The combined hexavalent diphtheria-tetanus-pertussis-hepatitis B-inactivated poliomyelitis - Haemophilus influenzae type b conjugate vaccine (Infanrix hexa™; DTPa-HBV-IPV/Hib: GlaxoSmithKline Vaccines) induces robust responses to the HBV component when administered at 3, 5 and 11-12 months of age. We assessed long term HBV antibody persistence 10-11 years after primary vaccination in infancy. METHODS: Antibody persistence and immune memory were assessed post-primary vaccination at 3, 5, 11-12 months with DTPa-HBV-IPV/Hib, or monovalent HBV vaccine (Engerix™ B, GlaxoSmithKline Vaccines) co-administered with DTPa-IPV/Hib (Infanrix™-IPV/Hib, GlaxoSmithKline Vaccines) in 185 children aged 11-12 years. Blood samples were collected before and 1 month after a challenge dose of Engerix™ B (10µg dose). RESULTS: 10-11 years after primary vaccination the percentage of subjects with persisting anti-HBs antibody concentrations ≥10mIU/ml was 48.4% in the DTPa-HBV-IPV/Hib group and 58.4% in the DTPa-IPV/Hib+HBV group. After the HBV challenge dose, the percentage with anti-HBs ≥100mIU/ml increased from 14.7% to 93.6% in the DTPa-HBV-IPV/Hib group and 19.1% to 94.4% in the DTPa-IPV/Hib+HBV group. Anti-HBs GMCs increased by at least 187-fold in each group. An anamnestic response (≥4-fold increase in initially seropositive or anti-HBs concentration ≥10mIU/ml in initially seronegative subjects) was observed in 96.8% and 96.6% of subjects in the DTPa-HBV-IPV/Hib and DTPa-IPV/Hib+HBV groups, respectively. No serious adverse events occurred that were considered related to challenge vaccination. CONCLUSION: Administration of HBV as part of a combination vaccine or as a monovalent vaccine induced long lasting immune memory against HBV in children primed at 3, 5 and 11 months of age. Antibody persistence and immune memory were similar, suggesting that protection afforded by DTPa-HBV-IPV/Hib and monovalent HBV vaccines, is likely to be of similar duration. The administration of HBV challenge dose 10-11 years after the 3, 5, 11-12 months primary schedule induced strong anamnestic responses and was well tolerated. This study is registered at www.clinicaltrials.govNCT01138098.

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 (Infanrix™ hexa) vaccine.

Protection against hepatitis B disease relies on either protective serum antibodies or on the ability of the immune system to mount an anamnestic response when confronted with the hepatitis B virus (HBV). This open multicenter study (EUDRACT: 2010-022538-10) measured antibodies to HBV surface antigen (anti-HBs) in 7-8-year-old children who had received 4 doses of hexavalent diphtheria-tetanus-acellular pertussis-HBV-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPa-HBV-IPV/Hib: Infanrix™ hexa; GlaxoSmithKline Vaccines) in the first 2 years of life through routine vaccine services in Germany. The ability of these children to mount an anamnestic response to a challenge dose of monovalent HBV vaccine (Engerix™ B Kinder; GlaxoSmithKline Vaccines) was also assessed. Before the challenge dose, 78.5% of children had anti-HBs levels ≥6.2 mIU/mL (seropositive) and 72.2% had anti-HBs levels ≥10 mIU/mL (seroprotected). Post-challenge, 98.9% had anti-HBs levels ≥10 mIU/mL and 95.8% had anti-HBs ≥100 mIU/mL. An anamnestic response to the challenge was observed in 96.6% of all subjects. The challenge dose was well tolerated, with a reactogenicity and safety profile consistent with published data. DTPa-HBV-IPV/Hib induces long-lasting immune memory to HBV that appears very similar to that induced by monovalent HBV vaccines. Protection against hepatitis B may be conferred through immune memory in subjects who responded to primary vaccination, even when they subsequently lose detectable levels of circulating anti-HBs antibodies.