Protective potential of hepatitis B virus antigens other than the S gene protein

The current recombinant hepatitis B vaccines are safe and effective. However, the occurrence of non-responders and difficulties in immunizing immunodeficient persons suggest the need for further improvements. Recent data suggest that the pre-S2 and pre-S1 domains of hepatitis B virus induce protective antibodies. The good T-helper cell response against pre-S1 epitopes would also improve the antibody response against the small surface antigen protein. An even better T-cell priming could be achieved by including hepatitis B core (HBc) proteins or peptides. An optimal immunogen would contain all three proteins comprising hepatitis B surface antigen in their natural conformation and glycosylation as well as the major T-cell epitopes of HBc.