Hepatitis B core antigen in the immunosuppressed chimpanzee

Two chimpanzees with low levels of anti-HBs developed increased antibody titres but showed no antigenemia after i.v. administration of 10 ml infective chimpanzee serum. Treatment of a chimpanzee (also possessing anti-HBs) i.m. with Cyclophosphamide plus Prednisolone for 3 weeks starting 2 days before the challenge with infective serum resulted in detectable circulating HBsAg by day 67. By day 95, the HBsAg concentration had increased to 17 times a human Ag reference plasma and low titres of anti-HBc were also present, but liver enzyme levels did not become abnormal until day 107. Since the circulating HBsAg concentration decreased gradually to 2 times the reference plasma by day 168, the animal was again immunosuppressed using oral Prednisolone alone for 7 weeks and then sacrificed. The liver yielded useful quantities of purified HBcAg while the plasma was an excellent source of Dane particles and HBsAg (41 X human reference plasma). This success could not be reproduced in 4 immunosuppressed cynomolgus monkeys. Our studies, therefore, demonstrate the value of the immunosuppressed high-order primate in the initiation and modulation of hepatitis B.