THE IN-VIVO PRODUCTION OF SPECIFIC HUMAN-ANTIBODIES BY VACCINATION OFHUMAN-PBL-SCID MICE

Human-PBL-SCID animals were created by intraperitoneal (i.p.) transfer of human peripheral blood lymphocytes (PBL) or PBL depleted of CD8-ex pressing lymphocytes (CD8dL). Analysis of human immunoglobulin levels in these animals revealed that severe combined immunodeficiency (SCID) mice receiving CD8dL produced significantly higher levels of serum hu man immunoglobulin than those receiving PBL. In an attempt to induce a ntigen-specific human antibodies these human-PBL-SCID animals were vac cinated with soluble protein antigen [ovalbumin (OVA)] entrapped withi n liposomes as an immunological adjuvant. Vaccination produced antigen -specific human IgM and IgG in human-PBL-SCID mouse serum. The use of liposomes as adjuvant and the reconstitution of animals with CD8dL tog ether enhanced the OVA-specific immune response as evidenced by the de tection of significantly increased serum antibody titres. In the CD8dL reconstituted group, solid tumours of human B-cell origin became dete ctable in the peritoneal cavity of animals at 8-10 weeks post-reconsti tution. These tumours were readily established in vitro and subsequent analysis of culture supernatants showed that these malignant cells co ntinue to secrete human antibodies specific for the original immunizin g antigen in vitro. We believe this vaccination of the human-PBL-SCID mouse to produce antigen-specific human antibodies, may find use in th e future production of human monoclonal antibodies and in the testing and development of novel vaccine/adjuvant systems.