Differences in the effectiveness of delivery of B- and CTL-epitopes incorporated into the Hepatitis B core antigen (HBcAg) c/e1-region

Work from a number of laboratories including our own has shown that foreign B-epitopes inserted into the c/e1-region of Hepatitis B core antigen (HBcA g) elicit powerful-antibody responses when mice are immunised with the reco mbinant core particles. In the present study, we wished to take advantage o f the immunodominance of the c/e1-region to deliver cytotoxic T-lymphocyte (CTL) epitopes as a recombinant HBcAg vaccine. Our results indicated that r ecombinant HBcAg containing CTL epitopes of the E7 protein of human papillo mavirus failed to prime E7-directed CTL responses when used to immunise mic e for antigen processing through either the endogenous pathway via a Salmon ella typhimurium vector, or through the exogenous pathway by parenteral imm unisation with recombinant core. Hydropathicity plots predict that the pres umed surface location of the hydrophilic c/e1-region within the core partic le may alter following insertion of hydrophobic residues constituting the C TL epitopes, thereby compromising their presentation to the efferent immune system. Our data indicate that while the c/e1-region has a powerful adjuva nting effect for inserted B-epitopes, it does not serve this function for i nserted CTL epitopes. These findings have generic implications for the deve lopment of CTL inducing vaccines using HBcAg as a vaccine vehicle.