Effects of cyclophosphamide on hepatitis B virus infection and challenge in chimpanzees

Abstract

The role of antibodies to the surface antigen of hepatitis B virus (HBsAg) and to the hepatitis B core antigen (HBcAg) and of cell-mediated immunity in hepatitis B virus infections and in resistance to challenge was studied in six chimpanzees. Two chimpanzees were studied during primary hepatitis B virus infection while being treated with cyclophosphamide (5-15 mg/kg im three times per week). Cyclophosphamide treatment may have predisposed these chimpanzees to chronic hepatitis B virus infections. Four other chimpanzees convalescent from primary hepatitis B virus infection (subtype ayw) were challanged with hepatitis Bvirus; two were callenged with heterologous virus (subtype adw) without immunosuppression, and two were challenged with homologous virus (subtype syw)while being treated with cyclophosphamide. Chimpanzees with residual humoral immunity, demonstrable by serum antibodies against the group determinant a and subdeterminant y of HBsAg, resisted challenge with either heterologous or homologous hepatitis B virus despite cyclophosphamide immunosuppression in the latter case. Antibodies to the hepatitis B virus core did not appear necessary for protection against hepatitis B virus infection in these chimps.