Document 0778
 DOCN  M9550778
 TI    Cloning and biological characterization of human single-chain Fv
       fragments that mediate neutralization of HIV-1.
 DT    9505
 AU    Srikantan V; Wang B; Satre MA; Ugen KE; Dang K; Scales F; Godillot AP;
       Williams WV; Weiner DB; Department of Pathology and Laboratory Medicine,
       University of; Pennsylvania School of Medicine, Philadelphia 19104.
 SO    AIDS. 1994 Nov;8(11):1525-32. Unique Identifier : AIDSLINE MED/95151228
 AB    OBJECTIVE: To develop recombinant single-chain Fv fragments against
       HIV-1 gp120. METHODS: A panel of human monoclonal antibody Fv fragments
       were generated against the HIV-1 gp120 by affinity selection from an
       antibody library expressed on the surface of filamentous phage. The
       library was prepared from peripheral blood lymphocytes of an
       asymptomatic HIV-1-infected mother with a high neutralization titer.
       This mother did not transmit HIV-1 to her offspring (non-transmitter).
       Heavy and light chains were initially amplified separately and combined
       by splicing by overlap extension to generate Fv fragments. RESULTS:
       Several clones expressing single-chain Fv fragments bind strongly to
       HIV-1 gp120 and several were found to neutralize cell-free HIV-1IIIB.
       Gross epitope mapping suggest that different clones bound to different
       functional regions on the envelope. The clones also exhibited sequence
       diversity. CONCLUSIONS: This strategy of cloning resulted in the
       development of functional human-derived antibody reagents with different
       anti-HIV-1 biological properties in vitro. These recombinant Fv
       fragments have potential utility as immune reagents, as well as in the
       design of potential immunotherapeutics. In addition, these antibody
       reagents may provide information on the relationship between humoral
       immunity and maternal-fetal (vertical) HIV-1 transmission.
 DE    Acquired Immunodeficiency Syndrome/PREVENTION & CONTROL/  *TRANSMISSION
       Amino Acid Sequence  Base Sequence  Cloning, Molecular  Disease
       Transmission, Vertical/*PREVENTION & CONTROL  DNA Primers  Enzyme-Linked
       Immunosorbent Assay  Female  Human  HIV Envelope Protein
       gp120/*IMMUNOLOGY  *HIV-1  Immunoglobulin
       Fragments/*BIOSYNTHESIS/THERAPEUTIC USE  Immunoglobulin Variable
       Region/BIOSYNTHESIS/THERAPEUTIC USE  Immunoglobulins,
       kappa-Chain/BIOSYNTHESIS  Immunoglobulins, Heavy-Chain/BIOSYNTHESIS
       Infant, Newborn  Lymphocytes/IMMUNOLOGY  Molecular Sequence Data
       Neutralization Tests  Polymerase Chain Reaction  Pregnancy  Pregnancy
       Complications, Infectious/*IMMUNOLOGY/VIROLOGY  Recombinant
       Proteins/*BIOSYNTHESIS/THERAPEUTIC USE  RNA Splicing  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).