Adoptive transfer of immunity to hepatitis B virus in mice by bone marrow transplantation from immune donors



Recipients of allogeneic bone marrow transplantation are immunosuppressed as a result of their primary disease and by myeloablative therapy. Such patients are dependent on multiple blood products and are at risk for hepatitis B virus infection. Active immunization against hepatitis B in the immediate pre- and post-transplant periods is ineffective, pre- sumably because of decreased T cell–dependent B-cell responses. This study was designed to evaluate, in a mouse model system, the transfer of immunity against hepatitis B to bone marrow transplant recipients through immunization of bone marrow donors against hepatitis B before transplantation. Bone marrow donor BALB/c mice were immunized with a recombinant hepatitis B vaccine. Seroconversion to HBs antibody occurred within 4 wk of primary immunization, and antibody levels in treated donor mice rose above 300 mIU/ml after a single booster injection. Bone marrow recipient mice, conditioned by sublethal irradiation, were injected intravenously with bone marrow cells obtained from syngeneic HBs antibody–positive immune donors. Antibody was detected in 10% of bone marrow recipients within 30 days of transplantation and in 56% 1 mo after a booster injection that led to a secondary rise in HBs antibody. Adoptive transfer of immunity to hepatitis B also occurred after transplantation of T cell–depleted bone marrow cells from hepatitis B–immune donors, albeit at a lower HBs antibody level. These results indicate that immunity to hepatitis B can be transferred in mice by bone marrow transplantation from hepatitis B–immune donors to immunosuppressed recipients. Furthermore, such bone marrow transplant recipients were able to respond to a booster immunization, suggesting secondary immune response in bone marrow recipients after primary response in donors. These data support the rationale for active vaccination of potential human bone marrow donors against hepatitis B, followed by booster vaccination to bone marrow recipients. (HEPATOLOGY 1993;17:955–959.)