Document 0133
 DOCN  M9550133
 TI    The in vivo production of specific human antibodies by vaccination of
       human-PBL-SCID mice.
 DT    9505
 AU    Walker W; Gallagher G; University Department of Surgery, Glasgow Royal
       Infirmary, U.K.
 SO    Immunology. 1994 Oct;83(2):163-70. Unique Identifier : AIDSLINE
       MED/95137632
 AB    Human-PBL-SCID animals were created by intraperitoneal (i.p.) transfer
       of human peripheral blood lymphocytes (PBL) or PBL depleted of
       CD8-expressing 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 human immunoglobulin than those receiving PBL. In an attempt to
       induce antigen-specific human antibodies these human-PBL-SCID animals
       were vaccinated with soluble protein antigen [ovalbumin (OVA)] entrapped
       within 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 together enhanced the OVA-specific immune response as evidenced by
       the detection of significantly increased serum antibody titres. In the
       CD8dL reconstituted group, solid tumours of human B-cell origin became
       detectable in the peritoneal cavity of animals at 8-10 weeks
       post-reconstitution. These tumours were readily established in vitro and
       subsequent analysis of culture supernatants showed that these malignant
       cells continue to secrete human antibodies specific for the original
       immunizing antigen in vitro. We believe this vaccination of the
       human-PBL-SCID mouse to produce antigen-specific human antibodies, may
       find use in the future production of human monoclonal antibodies and in
       the testing and development of novel vaccine/adjuvant systems.
 DE    Adjuvants, Immunologic  Animal  Antibodies, Bacterial/BIOSYNTHESIS
       Antibody Specificity  Antigenic Determinants/IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/IMMUNOLOGY  Female  Human  Immunoglobulins/*BIOSYNTHESIS
       Liposomes/IMMUNOLOGY  *Lymphocyte Transfusion  Lymphoma,
       B-Cell/IMMUNOLOGY  Mice  Mice, SCID  Ovalbumin/IMMUNOLOGY  Support,
       Non-U.S. Gov't  Tetanus Toxoid/IMMUNOLOGY  Transplantation,
       Heterologous/*IMMUNOLOGY  *Vaccination  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).