THE HEPATITIS-B VIRUS-SPECIFIC CTL RESPONSES INDUCED IN HUMANS BY LIPOPEPTIDE VACCINATION ARE COMPARABLE TO THOSE ELICITED BY ACUTE VIRAL-INFECTION

We have previously described the development of a lipopeptide-based va ccine, Theradigm-HBV, capable of inducing CTL responses in humans, Thi s vaccine incorporates the HLA-A2.1-restricted CTL. epitope hepatitis B core Ag 18-27, linked to the universal helper T lymphocyte (HTL) epi tope tetanus toroid (TT) 830-843. Herein, we report the results of a p hase I trial designed to examine the effects of Theradigm-HBV dose and regimen on the magnitude and duration of the memory CTL response, A t otal of four injections of up to 5 mg/dose were found to be a safe and effective means of generating substantial memory CTL responses, Precu rsor frequency analysis demonstrated CTL responses of similar magnitud e to those previously observed in patients who successfully cleared he patitis B virus infection and to influenza-specific memory CTL respons es induced by natural exposure to influenza virus, Theradigm-HBV induc ed CTL responses that persisted for more than 9 months after the last injection, HTL responses were associated with significant CTL response s, and sustained HTL activity was necessary for development of persist ent memory CTL activity. These results represent the first demonstrati on of the importance of HTL activity for development of long-lived mem ory CTL responses in humans, In conclusion, our results show that lipo peptides safely induce specific CTL activity in humans of such magnitu de and persistence as to be of potential therapeutic significance.