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

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 (H10 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. (HEPATOLOGY 1999;29: 954-959.)Taiwan is an endemic region for hepatitis B (HB). Before the implementation of a nationwide vaccination program in 1984, the hepatitis B virus (HBV) carrier rate in the general population was 15% to 20%. 1-2 The major impact of HB infection is its long-term sequelae, which may include chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. 3 Perinatal infection accounts for 40% to 50% of all HB infections and is responsible for the generation-to-generation transmission of HBV. 4 HB vaccines, both plasma derived and recombinant, are highly immunogenic and efficacious. 5-10 It has been reported that HB vaccine given soon after birth is able to protect infants from perinatal infection, and HB infection became the first disease model to show that mother-to-neonate transmission can be interrupted by an effective vaccine. 11 Taiwan started a national program of HB vaccination since 1984. This program resulted in a significant reduction of the HB carrier rate in children under 10 years from 9.8% before nationwide vaccination to 1.3% after the program. 12 It also decreased the incidence of hepatocellular carcinoma in children aged 6 to 9 years from 0.52 to 0.13 per 100,000. 13 However, the duration of protection provided by the...

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“…Among 127 antibody to hepatitis B core antigen (anti-HBc)-positive subjects, 4 became chronically infected. 8,9 These findings supported that, even in high-risk children, the protective effects of hepatitis B vaccination can last for at least 10 years. However, HBV breakthrough infection increased prominently thereafter.…”

“…Among children of HBsAg-carrier mothers, average incidence rates of HBV breakthrough infection for 5-10 years of age were similar to 8 or greater than 9 those of 1-5 years of age. The 10-year cumulative risk of HBV breakthrough infection were 11% 13%.…”

Determinants of Long-term Protection After Hepatitis B Vaccination in Infancy

“…natural boosting by close contact to the carrier mother during infancy is believed to be instrumental. 7,11,21,22,[29][30][31][32]35,37,38 the association between longer gap time between the last and preceding dose of primary vaccination has been discussed in several other studies. 29,33,[44][45][46] this may be explained by a more mature immune system in older infants 31,33 and maturation of the immune memory during the longer interval between the last 2 doses as shown for polio, hepatitis B and hepatitis a vaccine in children and adults.…”

“…Conclusions: Based on meta-analyses, predictors of waning immunity after hepatitis B vaccination in infancy could be identified. a prognostic model for long-term protection after hepatitis B vaccination in infancy was developed.Key Words: hepatitis B, infant vaccination, booster, long-term protection, determinants of protection (Pediatr Infect Dis J 2013;32: 307-313) A lthough hepatitis B vaccination is highly effective, vaccination failures leading to acute [1][2][3][4][5] and sometimes chronic infection [5][6][7][8] have been observed. although infections occurring within a short time interval after vaccination are likely to reflect primary vaccination failure 1,4 due to nonresponse, those occurring after decades are likely to reflect secondary vaccination failure due to waning immunity.…”

“…4,8,11,19,28,[31][32][33][34][35][36][37] Finally, both parameters may also be influenced by the prevalence of hepatitis B infection in the population and the HBsag carrier status of the mothers in the country. 6,7,11,21,22,[28][29][30][31][32][33]35,37,38 all these studies, however, are difficult to compare because results are influenced by a mixture of causes as well as by different follow-up periods.Based on a systematic review on studies providing information on the duration of anti-HBs ≥ 10 miu/ml persistence after hepatitis B vaccination started within the first 6 months of life and on the response to booster vaccination in individuals with antiHBs concentrations <10 miu/ml, we performed meta-analyses to identify relevant factors for duration of protection. a prognostic model to predict the proportion of vaccinated individuals likely to be protected is presented.…”