Long-term protection against HBV chronic carriage of Gambian adolescents vaccinated in infancy and immune response in HBV booster trial in adolescence.

Marianne A B Van Der Sande,Andrew J Hall,Samuel J Mcconkey,Pauline A Waight,Ebrima Bah,David Jeffries,Hilton C Whittle,Maimuna Mendy,Omar Sam,Pierre Hainaut,Aveika A Akum,Abi Kahn,Syed Zaman,Steve Kaye

doi:10.1371/journal.pone.0000753

Abstract

BackgroundChronic infection with hepatitis B virus (HBV) arising in childhood is associated with hepatocellular carcinoma in adult life. Between 1986 and 1990, approximately 120,000 Gambian newborns were enrolled in a randomised controlled trial to assess the effectiveness of infant HBV vaccination on the prevention of hepatocellular carcinoma in adulthood. These children are now in adolescence and approaching adulthood, when the onset of sexual activity may challenge their hepatitis B immunity. Thus a booster dose in adolescence could be important to maintain long-term protection.MethodsFifteen years after the start of the HBV infant vaccination study, 492 vaccinated and 424 unvaccinated children were identified to determine vaccine efficacy against infection and carriage in adolescence. At the same time, 297 of the 492 infant-vaccinated subjects were randomly offered a booster dose of HBV vaccine. Anti-HBs was measured before the booster, and two weeks and 1 year afterwards (ISRCTN71271385).ResultsVaccine efficacy 15 years after vaccination was 67.0% against infection as manifest by anti-HBc positivity (95% CI 58.2–74.6%), and 96.6% against HBsAg carriage (95% CI 91.5–100%). 31.2% of participants had detectable anti-HBs with a GMC of 32 IU/l. For 168 boosted participants GMC anti-HBs responses were 38 IU/l prior to vaccination, 524 IU/l two weeks after boosting, and 101 IU/l after 1 year.ConclusionsHBV vaccination in infants confers very good protection against carriage up to 15 years of age, although a large proportion of vaccinated subjects did not have detectable anti-HBs at this age. The response to boosting persisted for at least a year.Trial RegistrationControlled-Trials.com ISRCTN71271385

Highlights

Recent estimates indicate that more than a third of the world’s population, 2 billion people, have serological evidence of infection with hepatitis B virus (HBV)
It is estimated that at least half a million deaths per year are due to hepatitis B infection [1]. 10–15% of all adult male deaths in The Gambia are estimated to be related to hepatocellular carcinoma and chronic liver disease
This study aimed to evaluate long-term vaccine efficacy of infant vaccination in a large adolescent sample, as a follow-up within the original Gambia Hepatitis Intervention Study (GHIS) trial, representative of the general population, using concurrent unvaccinated controls, and to assess the immune response to an adolescent booster dose after 2 weeks and one year in the same population

Summary

Introduction

Recent estimates indicate that more than a third of the world’s population, 2 billion people, have serological evidence of infection with hepatitis B virus (HBV). Chronic infection with hepatitis B virus (HBV) arising in childhood is associated with hepatocellular carcinoma in adult life. Between 1986 and 1990, approximately 120,000 Gambian newborns were enrolled in a randomised controlled trial to assess the effectiveness of infant HBV vaccination on the prevention of hepatocellular carcinoma in adulthood. These children are in adolescence and approaching adulthood, when the onset of sexual activity may challenge their hepatitis B immunity. HBV vaccination in infants confers very good protection against carriage up to 15 years of age, a large proportion of vaccinated subjects did not have detectable anti-HBs at this age.

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