Cellular and humoral immune responses induced by intradermal or intramuscular vaccination with the major hepatitis B surface antigen

The vaccination route may influence the success of immunization against pat hogens. The conventional intramuscular (i.m.) application of a vaccine cont aining the hepatitis B virus (HBV) surface antigen (HBsAg) led to protectiv e anti-HBs antibody levels in the majority of vaccine recipients. In this s tudy, we vaccinated healthy volunteers and a group of i.m. vaccine nonrespo nders 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 H -3-thymidine uptake, enzyme-linked immunosorbent assay (ELISA) and enzyme-l inked immunospot assay (ELISPOT). The results were then compared with i.m. vaccinated controls. I.d. vaccinations were well tolerated and induced neut ralizing anti-HBs antibodies in all naive vaccine recipients and, important ly, all but one former i.m. nonresponder developed protective anti-HBs seru m antibody levels after 2 or 3 i.d. immunizations. On the cellular level, i .d. vaccine recipients showed significantly higher anti-HBs producing B-cel l frequencies and more vigorous class-II-restricted T-helper (Th) cell resp onses 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 HBs Ag via the i.d. route developed higher peptide-specific cytotoxic CD8 + T c ell precursor (CTLp) frequencies. In conclusion, i.d. HBsAg vaccination is more effective even in former i.m. vaccine nonresponders with respect to an tibody induction and specific B- and T-cell responses. The induction of vir us-specific CTLp may provide the rationale to study the i.d. HBsAg vaccine in the treatment of chronic hepatitis B.