Low hepatitis B immunogenicity of a hexavalent vaccine widely used in Germany: results of the German Health Survey for Children and Adolescents, 2003–2006

Abstract

SUMMARYThe success of childhood vaccination against hepatitis B relies on persistence of immunity into adolescence and adulthood. In 2000, two hexavalent vaccines with a hepatitis B component (Hexavac 1 , Infanrix hexa 1 ) were introduced in Germany. Hexavac was withdrawn in 2005 amidst concerns about its long-term hepatitis B protection. We compared hepatitis B surface antibody (anti-HBs) levels in children fully vaccinated with Hexavac or Infanrix hexa (n=477) in a secondary data analysis of a large cross-sectional health survey in Germany. On average 2 . 4 years after vaccination, 25 . 3 % of Hexavac vaccinees had anti-HBs levels <10 mIU/ml (95 % CI 19 . 0-32 . 8) compared to 4 . 7 % of Infanrix hexa vaccinees (95 % CI 2 . 4-8 . 9). These findings suggest that short-term hepatitis B immunogenicity in Hexavac vaccinees may also be weaker. Further studies are warranted to assess whether Hexavac vaccinees should be re-vaccinated or receive a booster vaccination before these birth cohorts reach adolescence.

Lasting immune memory against hepatitis B in 12–13-year-old adolescents previously vaccinated with 4 doses of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy

“…DTPa-HBV-IPV/Hib vaccination was introduced into the German routine immunization program in 2000; 10 primary vaccination of infants involves 3 vaccine doses at 2, 3 and 4 months of age, followed by a booster dose at 11–14 months 11 . In order to assess long-term antibody persistence and immune memory against HBV, we set up a series of 4 studies with increasing follow-up times of children who received 4 doses of DTPa-HBV-IPV/Hib in routine clinical practice.…”

Hepatitis B specific T cell immunity induced by primary vaccination persists independently of the protective serum antibody level

“…The protein content was 5 or 10 g dose in Hexavac or Infanrix vaccines, respectively. In 2005, in accordance with recommendations made by the European Medicines Agency, the Italian Drug Agency ordered the withdrawal of Hexavac due to concerns that the low antibody (Ab) titres elicited by the vaccine in children might not provide adequate protection against HBV during adolescence and later in life, when vaccinated subjects are at greater risk of exposure to the virus [6,7]. Because Hexavac had been used in Italy to immunize approximately 50% of infants born in 2002-2004, a multicentre study was undertaken to investigate the serological response to a booster dose of HB vaccine 5 years after primary immunization [8].…”

Recommendation for use of diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b conjugate, and hepatitis B vaccine in infants

“…21) It was presumed that the small amount of antigen (5 µg) contained in the vaccine did not provide long-term persistence of anti-HBs antibodies. 22,23) In contrast, another hexavalent vaccine (Infanrix ® -hexa; GSK), also licensed in Europe in 2000, which contains 10 µg of HBsAg, reportedly provides persistent protective immunity. Immunization with a standalone HepB vaccine at birth and a three-dose primary series with Hexaxim ® , which contains 10 µg of HBsAg, at 2, 4, and 6 months of age, reportedly induces a long-lasting anti-HBs antibody response and persistent immune memory up to 9-10 years of age, comparable with the results of immunization with Infanrix ® -hexa.…”