Objective: To determine the duration of protection conferred by the hepatitis B (HB) vaccination and the necessity of a booster dose. Methods: Immediately after the initial blood sampling, 252 youths (aged 18.8-20.5 years, 52% females) with a history of neonatal HB vaccination with one dose of the HB vaccine received a booster. Serum concentrations of antibodies against the HB surface antigen were assessed in samples collected before and 10-14 days after the booster. Seroconversion from concentrations <10 to ³10 IU/L were defined as a positive immune response. Results: Of the 252 participants, 131 were sero-susceptible and 114 responded. Conclusions: Nearly 90% of young people preserved their long-term protection; the results of this study do not support the use of an HB booster vaccination.

Keywords: Booster vaccination, HBV vaccine, Immune memory, Long-term protection.

Study participants were volunteers selected from a previous sero-epidemiological study in young adults who had been vaccinated 20 years earlier [12]. In that study, 510 youths with a documented history of complete HB vaccination starting at birth "as the first cohort of Iranian neonates involved in the national program" were the participants. In the present study, we randomly selected 252 people out of 510 cases of the former study. The study was approved by the Ethics Committees of the Mazandaran and Tehran Universities of Medical Sciences. Written informed consent was obtained prior to the study.

A total of 252 young adults with an age range from 18.8–20.5 years (52% females) were enrolled in this study. After excluding 9 participants with anti-HBc positivity, the relative proportion of allocated subjects in each group was as follows: G1, 88; G2, 43; G3, 41; and G4, 71 individuals. In the G4 participants, 41 (16.2%) showed antibody concentrations >300 IU/L. Ten to 14 days after the booster injection, 114 of 131 (87%) of the non-protected individuals mounted a positive immune response and were seroconverted. Participants whose pre-booster anti-HBs levels were from 2-9.9 IU/L had a higher probability of showing a response to boosting in comparison to participants levels <2 IU/L. Of the 41 participants in the G3 group, 39 (95.1%) showed an anamnestic response, and their post-booster MCA levels increased significantly (P=0.001). None of the G4 group responded to the booster. Finally, 90% of the participants retained their vaccine protection for 20 years.

To better determine the kinetics of vaccine-induced anti-HBs antibody titer and the prevalence of boostability among vaccinated subjects over time, a comparison was made between this study’s findings (a preservation rate of >44% seroprotection and an 87% response rate to boosting) and the results of our earlier study, which was performed 10 years ago in another region of the province [13] in the same cohort of Iranian infants vaccinated with the same vaccine and schedule. The results indicated that the prevalence of seroprotection rates decreased significantly but the boostability of the vaccinees did not change significantly. In this study, there was a direct correlation between pre-booster anti-HBs titers and the magnitude of the immune response to the booster injection; a lower response was seen in those with undetectable titers. Similar findings were earlier reported [14]. These findings may suggest that higher numbers of memory cells may be impaired or even disappeared in these vaccinated subjects.

The results of several long-term follow-up studies which investigated the persistence of specific antibodies and the presence of immune memory in persons vaccinated with different schedules and vaccines living in different settings of HB infection have been published [1-7]. While most studies have reported that nearly half of the vaccinees preserved their seroprotection 15-23 years after vaccination and the majority successfully responded to a booster vaccination (even those without detectable antibody titers) [1-4], some other studies have shown a very short duration of antibody persistence and poor immune memory [5-7]. Studies conducted in low-risk settings with comparable follow-up periods have generally shown lower rates of seroprotection and anamnestic responses than those in high-endemic countries. In a 15-year prospective study by Hammitt, et al. [5] only 5% of the vaccinated subjects preserved their seroprotection and an anamnestic response was observed in 51% of the boosted participants. These rates were 24% and 92%, respectively, in a study conducted in children in the United States by Middleman, et al. [4].

In contrast to most long-term prospective studies, in our cross-sectional study, the primary immune response and the initial anti-HBs antibody concentration achieved after priming were not studied. Therefore, our estimation for the natural boosting prevalence contained an arbitrary cut-off that may result in the under- or over-estimation of the natural boosting rate.

In conclusion, our study results indicate that infant HB vaccination provides long-term protection up through 20 years of age in the majority of vaccinated infants. These findings are in accordance with the current recommendation by most experts that a universal routine booster vaccination in the general population is not required for up to 20 years. However, the screening of vaccinated young adults at increased risk of exposure to HB infection to evaluate their immunity status and possible requirement for booster vaccination may still be required [9-11,15].

Acknowledgement: K. Shams-Esfandabad, J. Shojaei, and the health staff in the health centers affiliated with the Deputy of Health (Mazandaran University of Medical Sciences) for assistance in data collection and blood sampling; and M. Sotudeh-Anvari for her help with the laboratory testing and data collection.

Contributors: HS and MJS: conceptualization, design, data collection, and writing the paper; AA: design and laboratory testing; A-RK: statistical analysis.

Funding: Mazandaran and Tehran Universities of Medical Sciences; Competing interest: None stated.

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