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M94A1972.TXT
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1994-10-24
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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).