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M9550133.TXT
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1995-03-04
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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).