Low dose revaccination induces robust protective anti-HBs antibody response in the majority of healthy non-responder neonates

SummaryA sizeable proportion (1–10%) of healthy adults and to lesser extent neonates vaccinated with triple 10 μg hepatitis B (HB) vaccine fail to mount a protective antibody response. Revaccination with the same vaccine dose has proved to be effective in a significant number of primary non-responders. The influence of revaccination with lower vaccine doses however has not been studied adequately in non-responder neonates. This study was conducted to evaluate the influence of supplementary vaccination with a single low and standard dose of a recombinant hepatitis B (HB) vaccine in healthy Iranian non-responder neonates to primary vaccination.Iranian neonates unable to respond to primary vaccination with 10, 5 or 2.5 μg doses of recombinant HB vaccine were revaccinated with a single additional dose of the same concentration. Serum anti-HBs antibody titer was measured by sandwich ELISA. Administration of a single additional dose induced seroprotection (anti-HBs ≥ 10 IU/L) in 10/12 (83%), 10/12 (83%) and 21/24 (87.5%) of non-responder neonates in 10, 5 and 2.5 μg vaccine recipients with geometric mean titers (and 95% confidence limits) of 1358 (258–7142), 401 (79–2038) and 164 (62–433) IU/L, respectively. The log-transformed antibody titer obtained for the 10 μg dose recipients was significantly higher than that of the 2.5 μg dose vaccinees (p = 0.028). No significant differences in anti-HBs titer were observed between other groups of vaccinees. However, the total seroprotection rates obtained after administration of four low doses of 2.5 and 5 μg were significantly higher than that obtained after administration of the classical three 10 μg doses (p = 0.029 and p = 0.006, respectively). The total seroprotection rates were similar between all groups of vaccines receiving four doses of 2.5, 5 and 10 μg vaccine doses.These results indicate that a significant proportion of non-responder neonates can be induced to develop a protective anti-HBs response following revaccination with a single low dose vaccine. Thus adaptation of four low dose (2.5 or 5 μg) vaccination is expected to induce higher seroprotection rate and lower or comparable anti-HBs antibody titer in healthy neonates.