Long-term anti-HBs antibody persistence following infant vaccination against hepatitis B and evaluation of anamnestic response: a 20-year follow-up study in Thailand.

Hepatitis B vaccine has been available worldwide since the mid-1980s. This vaccine was evaluated in a clinical trial in Thailand, conducted on subjects born to hepatitis B surface antigen positive and hepatitis B e-antigen positive mothers and vaccinated according to a 4-dose schedule at 0, 1, 2 and 12 mo of age and a single dose of hepatitis B immunoglobulin concomitantly at birth. All enrolled subjects seroconverted and were followed for 20 y to assess the persistence of antibody to the hepatitis B surface antigen (anti-HBs) (NCT00240539). At year 20, 64% of subjects had anti-HBs antibody concentrations≥10 milli-international units per milli liter (mIU/ml) and 92% of subjects had detectable levels (≥3.3 mIU/ml) of anti-HBs antibodies. At year 20, subjects with anti-HBs antibody titer<100 mIU/ml were offered an additional dose of hepatitis B virus (HBV) vaccine to assess immune memory (NCT00657657). Anamnestic response to the challenge dose was observed in 96.6% of subjects with an 82-fold (13.2 to 1082.4 mIU/ml) increase in anti-HBs antibody geometric mean concentrations. This study confirms the long-term immunogenicity of the 4-dose regimen of the HBV vaccine eliciting long-term persistence of antibodies and immune memory against hepatitis B for up to at least 20 y after vaccination.

Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers.

This study assessed antibody persistence and immune memory to hepatitis B vaccine 20 y after priming with a recombinant hepatitis B virus (HBV) vaccine during infancy. Infants were vaccinated according to a 0, 1, 6 mo schedule with or without simultaneous administration of hepatitis B immunoglobulin (HBIg). Half of the subjects enrolled received an interim booster dose at year 5 (boosted) group, whereas the other half of the subjects enrolled did not (unboosted group). Antibody persistence was assessed until year 20. Immune memory was assessed by administration of a final HBV vaccine challenge dose at year 20 in a second study. At year 20, anti-HBs antibody concentration ≥ 10 mIU/ml rates and GMCs were higher among subjects in the boosted group (84.2% [16/19]; 95%CI: 60.4-96.6) when compared with those in the unboosted group [44.0% (11/25)]; 95% CI: 24.4-65.1). After the HBV vaccine challenge dose at year 20, anti-HBs anamnestic response for subjects in the unboosted and boosted groups was observed in 93.1% (95% CI: 77.2-99.2) and 100% (95% CI: 76.8-100) of subjects, respectively. The mean anti-HBs antibody concentration (GMC) was 562.0 mIU/ml (292.5-1079.7 mIU/ml) post administration of the challenge dose; this is a 28.5 fold increase from the pre- to post-challenge dose administration at year 20. This study demonstrates persistence of anti-HBs antibodies and presence of immune memory following hepatitis B vaccination for up to at least 20 y in Thailand. Immune memory was demonstrated for virtually all subjects, regardless whether they received they had received the additional HBV dose or not. The challenge dose at year 20 was well tolerated and a robust response was demonstrated. ClinicalTrials.gov Identifier: NCT00240526, NCT00774995.

Long-term anti-HBs antibody persistence and immune memory in children and adolescents who received routine childhood hepatitis B vaccination.

This paper presents data from two studies that evaluated 5-y and 10-y persistence of antibodies against hepatitis B (HBV) surface antigen (anti-HBs) and immune response to an HBV vaccine challenge in children and adolescents who had received three doses of a HBV vaccine in infancy as part of routine clinical practice [NCT00519649/NCT00984139]. Anti-HBs antibody concentrations ≥ 10 mIU/ml persisted in 83.3% (95% confidence interval [CI]: 78.5­87.5) and 78.3% (95% CI: 73.1­83.0) of subjects aged 7­8 y and 12­13 y, respectively 5­10 y after infant vaccination. One month postchallenge dose, 98.2% (95% CI: 95.9­99.4) and 93.7% (95% CI: 90.2­96.2) of subjects in the two age groups, respectively had anti-HBs antibody concentrations ≥ 100 mIU/ml. Overall, 99.6% (95% CI: 98­100) and 97.2% (95% CI: 94.5­98.8) of subjects aged 7­8 y and 12­13 y mounted an anamnestic response to the HBV challenge dose, which was well-tolerated. Healthy children aged 7­8 y and adolescents aged 12­13 y received three doses of a monovalent pediatric HBV vaccine (10 µg of HBsAg) before 18 mo of age. Serum samples collected before and one month post-HBV vaccine challenge dose were tested for anti-HBs antibody concentrations. Safety assessments were made for the HBV vaccine challenge dose. A three-dose childhood HBV immunization regimen induced persistence of antibodies against HBV infection for 10 y, up to adolescence. This vaccination regimen also conferred long-term immune memory against HBV as evidenced by the strong anamnestic response to the HBV vaccine challenge, despite waning anti-HBs antibody levels.

Seventeen-year antibody persistence in adults primed with two doses of an inactivated hepatitis A vaccine.

BACKGROUND AND OBJECTIVES: Antibody persistence and immune memory against hepatitis A (HAV) in adults in a low endemicity country, 15 y after immunisation with two doses of HAV vaccine has been demonstrated. This communication provides additional information on antibody persistence up to Year 17 from two of the longest follow-up studies [NCT00289757/NCT00291876]. METHODS: In two double-blind primary studies, healthy adults aged 17-40 y and 21-40 y, respectively received two doses of the HAV vaccine following a 0,6 mo or 0,12 mo schedule. Anti-HAV antibody concentrations were measured using an enzyme-linked immunoassay (cut-off: 15 mIU/ml) at Year 16 and Year 17. Subjects who became seronegative (anti-HAV < 15 mIU/ml) since previous reporting were offered a challenge dose, with anti-HAV antibody concentration measurements at Day 14 and Day 30 thereafter. RESULTS: At Year 17, 100% and 96.7% of subjects remained seropositive for anti-HAV antibodies following the 0, 6 mo and 0, 12 mo regimens, respectively (GMCs: 278 mIU/ml and 369 mIU/ml). One subject who became seronegative at Year 16 received a HAV challenge dose within the next 12 mo and mounted an anamnestic response. The challenge dose was well-tolerated. CONCLUSIONS: Both HAV immunisation regimens (0,6 mo and 0,12 mo) induced persistence of vaccine-induced antibodies against HAV for at least 17 y after primary vaccination.

Anti-HBs antibody persistence following primary vaccination with an investigational AS02(v)-adjuvanted hepatitis B vaccine in patients with renal insufficiency.

BACKGROUND: Three doses of the investigational AS02(v)-adjuvanted hepatitis B virus (HBV) vaccine HB-AS02 have been shown to induce more rapid seroprotection and higher anti-HBs antibody concentrations in patients with renal insufficiency than four doses of FENDrix™ (HB-AS04), an adjuvanted HBV vaccine licensed in Europe for use in this population. This study evaluated persistence of immune response up to 36 months after primary vaccination. METHODS: In this open, international, Phase III follow-up study, 151 pre-dialysis, peritoneal dialysis and hemodialysis patients ≥15 years of age received HB-AS02 at 0, 1, 6 months and 149 received HB-AS04 at 0, 1, 2, 6 months. Of these, 99 and 80 returned at Month 36, 76 and 62 of whom were eligible for inclusion in the Long-Term According-To-Protocol (LT-ATP) cohort for descriptive analysis of antibody persistence (mean age: 65.6 years). RESULTS: At Month 36, 89.5% of subjects in the HB-AS02 group and 72.6% of those in the HB-AS04 group had anti-HBs antibody concentrations ≥10 mIU/ml. Anti-HBs antibody concentrations were ≥100 mIU/ml in 82.9% and 35.5% of subjects, respectively. Anti-HBs geometric mean antibody concentrations were higher in the HB-AS02 group over the 36 months of follow-up. An exploratory "time to boost" analysis confirmed that subjects who received HB-AS02 were 2.54 times more likely than those who received HB-AS04 to have anti-HBs antibody concentrations ≥10 mIU/ml at Month 36 (p=0.013 [95% CI: 1.22, 5.31]). CONCLUSION: HB-AS02 candidate vaccine induces high and persistent anti-HBs antibody levels in pre-dialysis, peritoneal dialysis and hemodialysis patients, potentially reducing the need for booster doses in this population.