       Document 0239
 DOCN  M9630239
 TI    Presentation of HIV V3 loop epitopes for enhanced antigenicity,
       immunogenicity and diagnostic potential.
 DT    9603
 AU    Fontenot JD; VanCott TC; Parekh BS; Pau CP; George JR; Birx DL;
       Zolla-Pazner S; Gorny MK; Gatewood JM; Theoretical Biology and
       Biophysics and Life Sciences Division,; Los Alamos National Laboratory,
       New Mexico.
 SO    AIDS. 1995 Oct;9(10):1121-9. Unique Identifier : AIDSLINE MED/96098127
 AB    OBJECTIVE: To evaluate the immunological properties of a panel of human
       mucin MUC1/HIV V3 loop chimeras. DESIGN: The immunodominant epitope of
       MUC1 (APDTR) was found to be structurally isomorphous with the tip of
       the principle neutralizing determinant (PND) of HIV-1 (MN) (GPGRA). A
       panel of 120 residue, six tandem repeat (TR) and 60 residue, three TR
       chimeric antigens were constructed in which the repeating MUC1 epitope
       is replaced by HIV-1 PND. Each 20 residue TR contains one PND epitope.
       The PND of HIV-1 is presented in the native beta-turn conformation at
       the crest of each repeating knob structure of the mucin-like protein.
       METHODS: The antigenicity of the chimeric antigens were compared using
       enzyme-linked immunosorbent assay (ELISA) and HIV-infected patient sera.
       Structural effects of antibody-antigen interactions were determined
       using surface plasmon resonance, with human monoclonal antibodies,
       chimeric antigens and the cyclic and linear V3 loops. Immunogenicity of
       three versus six TR was measured in mice. RESULTS: Nine residues of the
       HIV PND substituted into the mucin backbone were equivalent to the 36
       residue cyclic V3 loop in ELISA. The 120 residue antigens induced high
       titer, immunoglobulin (Ig) M and IgG, and HIV-specific antibodies in
       mice. CONCLUSIONS: MUC1/V3 chimeras efficiently detect HIV-specific
       antibodies in patient sera. Multivalent presentation of the PND is
       advantageous for higher affinity antibody-antigen interactions and for
       inducing HIV-specific IgM and IgG antibodies.
 DE    Amino Acid Sequence  Animal  Antibodies, Monoclonal  Antibody
       Specificity  AIDS Serodiagnosis/METHODS  Chimeric Proteins/IMMUNOLOGY
       Female  Human  HIV Antibodies/*IMMUNOLOGY/METABOLISM  HIV Envelope
       Protein gp120/CHEMISTRY/*IMMUNOLOGY/METABOLISM  HIV-1/*IMMUNOLOGY
       IgG/BIOSYNTHESIS  IgM/BIOSYNTHESIS  Immunodominant
       Epitopes/ANALYSIS/*IMMUNOLOGY  Kinetics  Mice  Mice, Inbred BALB C
       Molecular Sequence Data  Mucins/CHEMISTRY/IMMUNOLOGY  Peptide
       Fragments/CHEMISTRY/*IMMUNOLOGY/METABOLISM  Repetitive Sequences,
       Nucleic Acid  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       JOURNAL ARTICLE

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

