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M9490759.TXT
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1994-09-24
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Document 0759
DOCN M9490759
TI Comparison of the immune response to recombinant gp120 in humans and
chimpanzees.
DT 9411
AU Berman PW; Eastman DJ; Wilkes DM; Nakamura GR; Gregory TJ; Schwartz D;
Gorse G; Belshe R; Clements ML; Byrn RA; Department of Immunology,
Genentech Inc., South San Francisco,; California 94080.
SO AIDS. 1994 May;8(5):591-601. Unique Identifier : AIDSLINE MED/94338594
AB OBJECTIVE: To assess similarities and differences in antibody responses
to recombinant (r) HIV-1IIIB gp120 in chimpanzees, previously protected
from HIV-1 infection, and human volunteers immunized in connection with
a Phase I clinical trial. METHODS: Frozen sera from humans immunized
with rgp120 from HIV-1IIIB and chimpanzees immunized with the same
antigen or recombinant soluble gp160 were compared in a variety of
serologic assays. RESULTS: The magnitude of the antibody response to
gp120 was similar in both species; however, the half-life of the
antibody response to rgp120 was approximately 4.5 times longer in humans
(9 weeks) than in chimpanzees (2 weeks). Antibodies to gp120 in both
species were broadly cross-reactive with gp120 from diverse isolates of
HIV-1 and were effective in blocking the binding of gp120 to CD4.
Antibody binding to native gp120 was greater than to denatured gp120 in
both species. Antibody responses to the principal neutralizing
determinant (V3 domain) and virus neutralization titers were
approximately 10-fold lower in humans than chimpanzees. The relative
avidity of antibody binding to gp120 was higher in the sera from the
immunized chimpanzees than in the immunized humans. CONCLUSIONS: While
the antibody responses to rgp120 elicited in man and chimpanzees were in
many ways similar, significant differences did occur. Predictions made
on the basis of chimpanzee immunogenicity studies over-estimated the
potency of the virus neutralizing titers and under-estimated the
duration of the antibody response achieved in humans.
DE Amino Acid Sequence Animal Antibody Affinity Antigenic
Determinants/CHEMISTRY/IMMUNOLOGY AIDS Vaccines/*IMMUNOLOGY Chimpansee
troglodytes/*IMMUNOLOGY Comparative Study Cross Reactions Female
Human HIV Antibodies/*BIOSYNTHESIS/IMMUNOLOGY HIV Envelope Protein
gp120/CHEMISTRY/*IMMUNOLOGY HIV-1/CLASSIFICATION/*IMMUNOLOGY Male
Molecular Sequence Data Neutralization Tests Peptide
Fragments/IMMUNOLOGY Protein Binding Protein Structure, Secondary
Recombinant Proteins/*IMMUNOLOGY Species Specificity Support, U.S.
Gov't, P.H.S. Vaccination CLINICAL TRIAL JOURNAL ARTICLE RANDOMIZED
CONTROLLED TRIAL
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).