       Document 1972
 DOCN  M94A1972
 TI    A miniantibody to HIV neutralizes HIV strains.
 DT    9412
 AU    Levi M; Hinkula J; Ruden U; Osterhaus A; Wigzell H; Wahren B; Dept.
       Clin. Virol., Karolinska Institute, Stockholm, Sweden.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):41 (abstract no. 139A). Unique
       Identifier : AIDSLINE ICA10/94370603
 AB    OBJECTIVE: To reveal important regions of HIV neutralizing antibodies.
       METHODS: A complementarity-determining region (CDR) of the mouse
       monoclonal antibody (mAb) F58 was constructed with specificity to a
       neutralization-inducing region of human immunodeficiency virus type 1
       (HIV-1). The mAb has its major reactivity to the amino acid sequence
       I-GPGRA in the V3 viral envelope region. All CDRs including several
       framework amino acids were synthesized from the sequence deduced by
       cloning and sequencing mAB F58 heavy- and light-chain variable domains.
       RESULTS: Peptides derived from the third heavy-chain domain (CDR-H3)
       alone or in combination with the other CDR sequences competed with F58
       mAb for the V3 region. The CDR-H3 peptide was chemically modified by
       cyclization, substitution or deletion and then inhibited HIV-1
       replication as well as syncytium formation by infected cells. Both the
       homologous IIIB viral strain to which the F58 mAb was induced and the
       heterologous SF2 strain were inhibited. Passive immunization of
       HIV-challenged immunodefective mice and eleven HIV infected patients
       indicated an in vivo HIV inhibitory effect of the parental monoclonal
       antibody. CONCLUSION: This synthetic peptide had unexpectedly potent
       antiviral activity and may be a potential tool for treatment of HIV
       infected persons.
 DE    Amino Acid Sequence  Animal  Antibodies, Monoclonal/GENETICS/*IMMUNOLOGY
       Antiviral Agents/THERAPEUTIC USE  Genes, Immunoglobulin  Human  HIV
       Antibodies/*BIOSYNTHESIS/GENETICS/IMMUNOLOGY  HIV-1/*IMMUNOLOGY
       Immunoglobulin Variable Region/*BIOSYNTHESIS  Mice  MEETING ABSTRACT

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

