Long–Term Response to Hepatitis B Vaccination and Response to Booster in Children Born to Mothers With Hepatitis B E Antigen

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Abstract
Hepatitis B (HB) vaccine provides an uncertain duration of protection and the optimal timing of booster vaccine remains unclear. This study examined the immune response at 10 years of 118 children who had developed protective anti–HB surface (anti–HBs) levels after a primary series of HB immunizations in infancy. All of the children were born to hepatitis B e Antigen (HBeAg)–positive hepatitis B surface antigen (HBsAg) carrier mothers. HB markers in all subjects and cellular immune response in some were determined. A booster was given to all subjects after the collection of samples and another blood sample was collected 4 weeks later. The results showed that a total of 39 (33%) of the children were seronegative for anti–HBs. T–cell proliferative response to HBsAg was noted in 47% of children. On HBsAg stimulation, leukocyte samples from a significantly higher proportion of subjects produced cytokines (81% of T cells produced interleukin–2 [IL–2] and 100% produced IL–5). The booster dose of HB vaccine induced the production of a protective level of anti–HBs (≥10 mIU/mL) in all subjects. Cellular immunity was augmented with a positive rate of 58%, 90%, and 100% for HBsAg–induced T–cell proliferation, IL–2 production, and IL–5 production, respectively. Although 14 (11.9%) of the subjects were HB core antibody positive at 10 years of age, no new HBsAg carrier was detected. The results of this study show that protection afforded by HB vaccination persisted to the age of 10 years in all vaccinees. Immunologic memory was detected in all subjects including those who had lost their anti–HBs seropositivity. These results suggest that no booster vaccination is needed before 10 years of age. The most sensitive marker of immunologic memory is IL–5 production of T cells.