       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).

