title: Hepatitis B specific T cell immunity induced by primary vaccination persists independently of the protective serum antibody level.
abstract: 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.
authors.affiliation: Anti-Infectious Immunity Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Carollo
authors.forename: Raffaella
authors.initials: R
authors.lastname: Palazzo
authors.forename: Manuela
authors.initials: M
authors.lastname: Bianco
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pandolfi
authors.forename: Paola
authors.initials: P
authors.lastname: Chionne
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fedele
authors.forename: Alberto Eugenio
authors.initials: AE
authors.lastname: Tozzi
authors.forename: Rita
authors.initials: R
authors.lastname: Carsetti
authors.forename: Luisa
authors.initials: L
authors.lastname: Romanò
authors.forename: Clara Maria
authors.initials: CM
authors.lastname: Ausiello
mesh_terms: D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D007558:Italy; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology
chemical_list: D016207:Cytokines; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; C426944:Hexavac; D011054:Poliovirus Vaccine, Inactivated; D017778:Vaccines, Combined; C541235:diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine