VACCINE TO TREAT CHRONIC HEPATITIS B VIRUS INFECTION

HEPATITIS B VIRUS (HBV) IS A HEPATOTROPIC VIRUS THAT IS A MAJOR PUBLIC HEALTH CONCERN WORLDWIDE. WHILE A RECOMBINANT SURFACE ANTIGEN VACCINE IS AVAILABLE, THERE IS NO EFFECTIVE TREATMENT FOR THE MILLIONS OF INDIVIDUALS WHO ARE CHRONICALLY INFECTED. THE OBJECTIVE IS TO DEVELOP PEPTIDE THERAPEUTICS THAT WILL GENERATE CYTOTOXIC T LYMPHOCYTES (CTL) IN VIVO AND MAY AMELEIORATE CHRONIC HBV INFECTIONS. THESE MOLECULES MAY ALSO BE USEFUL AS PROPHYLACTIC VACCINES. THIS STUDY AIMS TO (1) DEFINE THE 9-10 AMINO ACIDS THAT CONSTITUTE THE CORE CTL EPITOPES, (2) MODIFY THESE PEPTIDES TO ENHANCE THEIR STABILITY, FACILITATE UPTAKE INTO ANTIGEN PRESENTING CELLS AND ENHANCE IMMUNOGENICITY BY ADDING HELPER EPITOPES, AND (3) DETERMINE IF THESE PEPTIDES CAN GENERATE CTL'S IN VIVO (IN HLA-A2 TRANSGENIC MICE). DURING THE PHASE I STUDY, RESEARCH EFFORTS WILL BE CONDUCTED ON EACH OF THE THREE SPECIFIC AIMS. WE WILL IDENTIFYTHE OPTIMAL LENGTH CYTOTOXIC T CELL ANTIGENIC PEPTIDE, HBCAG 18-27, CHEMICALLY MODIFY IT AND DEMONSTRATE THE IMMUNOGENICITY OF THE MODIFIED PEPTIDE IN HLA-A2 TRANSGENIC MICE IN THE ABSENCEOF ADDED ADJUVANTS. WE WILL DEMONSTRATE THE FEASIBILITY OF OUR ULTIMATE GOAL OF PRODUCING A THERAPEUTIC VACCINE FOR THE TREATMENT OF CHRONIC HEPATITIS B VIRUS INFECTION.