A pilot study of the CY-1899 T-cell vaccine in subjects chronically infected with hepatitis B virus

Clinical observations suggest that eradication of the hepatitis B virus (HB V) is immune-mediated. Vigorous cytotoxic T lymphocyte (CTL) activity direc ted at HLA class I-bound viral epitopes are detected during acute hepatitis B, but not in chronic hepatitis B carriers. A CTL epitope derived from the hepatitis B core protein amino acids 18-27 has been incorporated into a va ccine also comprised of a T-helper cell epitope and 2 palmitic acid residue s (CY-1899). The aim of this study was to determine whether repeated doses of CY-1899 given to patients with chronic hepatitis B could initiate in viv o CTL activity and viral clearance. Patients with chronic hepatitis B recei ved up to 4 doses (ranging from 0.05 mg to 15 mg) 6 weeks apart. Following vaccination, patients were monitored for hepatitis B surface antigen and "e " status, HBV-DNA levels, liver biochemistry, CTL activity, and any adverse events. Ninety patients with chronic hepatitis B infection received CY-189 9. Mean CTL responses were all low but were maximal following vaccination w ith 5 mg CY-1899. Peak CTL responses never exceeded 10 lytic units (LU) reg ardless of vaccine dose, this value being well below that seen following re solution of acute hepatitis B, No significant changes in liver biochemistry or viral serology were observed during follow-up. No serious adverse event s were noted. Administration of the single-epitope vaccine, CY-1899, initia ted CTL activity, but of a magnitude lower than that observed during sponta neous HBV clearance. This low-level CTL activity was not associated with vi ral clearance.