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

In 2005, in accordance with recommendations made by the European Medicines Agency, the Italian Drug Agency ordered withdrawal of the hexavalent Hexavac® vaccine (Sanofi Pasteur MSD) from the market. Concerns had been raised about the low immunogenicity of the hepatitis B virus component of the vaccine, assessed by measurement of serum antibody levels, and its potential consequences on long-term protection against hepatitis B infection. We evaluated memory T cell response to establish whether there are differences in the protective mechanisms among children who had received either Hexavac® or Infanrix-hexa® (GlaxoSmithKline) as their primary vaccination. Immunological memory was determined by measuring the ability of T cells to proliferate and secrete IFNγ by ELISA and intracellular cytokines (IFNγ and IL-2) when cultured with hepatitis B surface antigen (HBsAg). The different memory subsets of T cells were also measured.The results indicate that, although they generate different serum antibody levels, both vaccines are efficient in generating T recall responses in vitro five years after the primary vaccination. The less immunogenic Hexavac® vaccine induces a strong T antigen response, as indicated by increased blast proliferation and the enhanced presence of memory subsets after HBsAg recall stimulation. These findings suggest that cellular immune response should be considered alongside serological markers as a surrogate of protection.

► Concerns about immunogenicity of hepatitis B virus component of Hexavac vaccine. ► T response to establish differences in Hexavac/Infanrix primary vaccinated children. ► Both vaccines are efficient in generating T recall responses 5 years after vaccination. ► Less immunogenic Hexavac induces strong HBsAg recall proliferation/memory subsets. ► Cellular immune and serological responses are important as surrogate of protection.