title: Cellular and humoral immune responses induced by intradermal or intramuscular vaccination with the major hepatitis B surface antigen.
abstract: The vaccination route may influence the success of immunization against pathogens. The conventional intramuscular (i.m.) application of a vaccine containing the hepatitis B virus (HBV) surface antigen (HBsAg) led to protective anti-HBs antibody levels in the majority of vaccine recipients. In this study, we vaccinated healthy volunteers and a group of i.m. vaccine nonresponders via the intradermal (i.d.) route and analyzed the HBV-specific B-cell response as well as class-II- and class-I-restricted T-cell responses by (3)H-thymidine uptake, enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT). The results were then compared with i.m. vaccinated controls. I.d. vaccinations were well tolerated and induced neutralizing anti-HBs antibodies in all naive vaccine recipients and, importantly, all but one former i.m. nonresponder developed protective anti-HBs serum antibody levels after 2 or 3 i.d. immunizations. On the cellular level, i.d. vaccine recipients showed significantly higher anti-HBs producing B-cell frequencies and more vigorous class-II-restricted T-helper (Th) cell responses than i.m. controls. However, although the HBsAg-specific T cells were characterized by their cytokine release as Th1-like cells in both groups, human leukocyte antigen (HLA)-A2+ individuals who received the soluble HBsAg via the i.d. route developed higher peptide-specific cytotoxic CD8+ T cell precursor (CTLp) frequencies. In conclusion, i.d. HBsAg vaccination is more effective even in former i.m. vaccine nonresponders with respect to antibody induction and specific B- and T-cell responses. The induction of virus-specific CTLp may provide the rationale to study the i.d. HBsAg vaccine in the treatment of chronic hepatitis B.
authors.affiliation: I. Department of Internal Medicine, Johannes-Gutenberg-University, Mainz, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Rahman
authors.forename: A
authors.initials: A
authors.lastname: Dahmen
authors.forename: S
authors.initials: S
authors.lastname: Herzog-Hauff
authors.forename: W O
authors.initials: WO
authors.lastname: Böcher
authors.forename: P R
authors.initials: PR
authors.lastname: Galle
authors.forename: H F
authors.initials: HF
authors.lastname: Löhr
mesh_terms: D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014611:Vaccination
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D015395:Histocompatibility Antigens Class I