Cytotoxic T lymphocyte (CTL) activity and CD4+ helper T cell responses to the hepatitis B virus (HBV) core
antigen (
HBcAg) have been implicated in clearance of acute and chronic HBV
infections. We showed that
intramuscular injections of a novel recombinant retroviral vector expressing an
HBcAg-
neomycin phosphotransferase II (HBc-NEO) fusion
protein induces HBc/eAg-specific
antibodies and CD4+ and CD8+ T cell responses in mice and rhesus monkeys. We have now immunized three chronically infected chimpanzees, each with 10(10) CFU of nonreplicating retroviral vector particles expressing the HBc-NEO fusion
protein. Of two immunized chimpanzees examined for CTL responses, one developed
HBcAg-specific CTLs and showed marginal, transient elevations of
alanine aminotransferase (ALT) levels following injection. However, both chimpanzees remained positive for serum
HBeAg, negative for anti-HBe antibody by conventional assays, and displayed no change in HBV viral load throughout the study. In contrast, the third chimpanzee exhibited a traditional seroconversion evidenced by a loss of serum
HBeAg and the subsequent emergence of anti-HBe
antibodies within 24 weeks after the first injection. Simultaneously, two transient ALT flares and a significant decrease in the serum HBV
DNA levels were noted. Despite its limitations, the present study demonstrates (1) the safety of treatment with high titers of retroviral vector in chimpanzees, (2) the capability of a retroviral vector expressing
HBcAg to stimulate immune responses in HBV chronic carrier chimpanzees, and (3) that retroviral vector immunization may be therapeutically beneficial in the treatment of chronic HBV
infection.