IN-VITRO T-CELL IMMUNE-RESPONSES TO THE PRES2-ANTIGEN OF THE HEPATITIS-B VIRUS ENVELOPE PROTEIN IN PRES2-VACCINE RECIPIENTS - ABSENCE OF CROSS-REACTIVITY OF SUBTYPES AT A MAJOR T-CELL RECOGNITION SITE(S)

The immune responses to hepatitis B virus envelope antigen were invest igated in 16 vaccine recipients after immunization with a recombinant yeast-derived preS2+S (adw) vaccine for hepatitis B virus. After the c ompletion of the three-shot immunization series, all vaccine recipient s developed antibody to the S domain and anti-preS2 antibody. In vitro proliferative responses to preS2 (120-174) peptide were demonstrated in 10 of 16 vaccine recipients. Although reactivity could be demonstra ted through the length of the preS2 peptide, the principal site of pro liferative activity was contained within the preS2 (146-165) region of the peptide. The principal T cell reactive site coincides with a regi on of significant amino acid variability of the different hepatitis B virus serotypes. Cross-reactivity with a serotype (ayw) not present in the preS2+S vaccine could not be demonstrated at this widely recogniz ed T cell epitope. The low level of cross-reactivity demonstrated in a limited subset of the vaccine recipients was mediated through nondomi nant T cell reactive sites contained in the relatively conserved preS2 (120-146) region of the molecule. The identification of widely recogn ized but serotype-specific T cell epitopes in the preS2 region of the hepatitis B virus envelope antigen may be an important consideration i n future vaccine development.