A retrospective pooled analysis assessing the effect of age on the immunogenicity of Havrix™ in healthy adults

Over recent decades, the global incidence of hepatitis A virus infection has been reduced by improvements in sanitation infrastructure and through immunization programs. The immunogenicity and field efficacy of the inactivated hepatitis A vaccine (Havrix™, GSK, Belgium) has been demonstrated in clinical trials, population-impact studies as well as in several outbreak settings. However, immunological data in older populations are limited, with only few studies assessing the immune response of this vaccine in adults aged ≥40 years. This retrospective pooled analysis of 4 2-dose primary vaccination studies compared the immunogenicity and safety of the inactivated hepatitis A vaccine in adults aged ≥40 years with subjects aged 20–30 years (control group; N = 80 in each group). Fifteen days after the first vaccine dose, 79.7% (95% CI: 68.8–88.2) and 92.3% (95% CI: 84.0–97.1) of subjects were seropositive in the ≥40 years and control groups, respectively; 97.5% (95% CI: 91.2–99.7) and 97.4% (95% CI: 91.0–99.7), respectively, were seropositive one month after the first dose. All subjects in both groups (95% CIs: 95.4–100 and 95.3–100, respectively) were seropositive one month after the second dose. Safety profiles were similar in both groups. In conclusion, the inactivated hepatitis A vaccine induced similar immune responses in adults aged ≥40 and 20–30 years one month after the first and second dose whereas younger subjects may demonstrate a higher seroconversion rate 15 days after the first dose.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Characterization of an age-response relationship to GSK's recombinant hepatitis B vaccine in healthy adults: An integrated analysis.

The immune system becomes less effective with age, and older age is associated with an increased susceptibility to diseases and reduced responses to vaccination. Furthermore, some adult populations, such as those with diabetes mellitus, are at increased risk of acute hepatitis B virus (HBV) infection. Decreasing responses to vaccination with advanced age have been described, but it is not known at what age immunogenicity starts to reduce, or until what age immunogenicity remains acceptable (for example ≥ 80% seroprotection post-vaccination). We characterized the relationship between age and seroprotection rate induced by recombinant HBV vaccination by conducting a pooled analysis of clinical trial data. Healthy adults aged ≥ 20 y who had been vaccinated with 20 μg HBV vaccine (Engerix™ B, GSK Vaccines, Belgium) in a 0, 1, 6 months schedule in 11 studies since 1996 were included. The observed seroprotection rate, defined as an anti-HBV surface antigen antibody concentration ≥ 10 mIU/ml was 94.5% in the whole population (N = 2,620, Total vaccinated cohort), ranging from 98.6% in adults vaccinated at age 20-24 years, to 64.8% in those vaccinated at age ≥ 65 y A model on seroprotection rates showed a statistically significant decrease with age, and predicted that the anti-HBs seroprotection rate remains ≥ 90% up to 49 y of age and ≥ 80% up to 60 y of age. Individuals at risk of HBV infection should be vaccinated as early in life as possible to improve the likelihood of achieving seroprotection. Additional studies are needed to identify whether unvaccinated individuals older than 60 y would benefit from regimens that include additional or higher vaccine doses.info:eu-repo/semantics/publishe

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: 15mIU/ml) at Year 16 and Year 17. Subjects who became seronegative (anti-HAV < 15mIU/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: 278mIU/ml and 369mIU/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

Persistence and immune memory to hepatitis B vaccine 20 y 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

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