Document 0784
 DOCN  M9590784
 TI    Synergistic inhibition of human immunodeficiency virus type 1 envelope
       glycoprotein-mediated cell fusion and infection by an antibody to CD4
       domain 2 in combination with anti-gp120 antibodies.
 DT    9509
 AU    Burkly L; Mulrey N; Blumenthal R; Dimitrov DS; Biogen Inc, Cambridge,
       Massachusetts 02142, USA.
 SO    J Virol. 1995 Jul;69(7):4267-73. Unique Identifier : AIDSLINE
       MED/95287480
 AB    Antibodies to several epitopes of the human immunodeficiency virus type
       1 (HIV-1) envelope glycoprotein (gp120-gp41) can synergize in inhibiting
       HIV-1 infection. In the present study we tested the ability of a
       monoclonal antibody (MAb), 5A8, which interacts with CD4 domain 2, and
       other CD4-specific MAbs to synergize with antibodies against gp120. We
       have previously found that 5A8 inhibits HIV-1 entry without interfering
       with gp120 binding to CD4, presumably by affecting a postbinding
       membrane fusion event. Because antibodies to the gp120 V3 loop also
       affect post-CD4-gp120-binding events, 5A8 was first tested in
       combination with anti-V3 loop antibodies for possible synergy. The
       anti-V3 loop antibodies 0.5 beta, NEA-9205, and 110.5 acted
       synergistically with 5A8 in inhibiting syncytium formation between
       gp120-gp41- and CD4-expressing cells. A human MAb to an epitope of gp120
       involved in CD4 binding, IAM 120-1B1, and another anti-CD4 binding site
       antibody, PC39.13, also exerted synergistic effects in combination with
       5A8. Similarly, an antibody against the gp120 binding site on CD4, 6H10,
       acted synergistically with an anti-V3 loop antibody, NEA-9205. However,
       a control anti-CD4 antibody, OKT4, which does not significantly inhibit
       syncytium formation alone, produced only an additive effect when
       combined with NEA-9205. Serum from HIV-1-infected individuals, which
       presumably contains antibodies to the V3 loop and the CD4 binding site,
       exhibited a strong synergistic effect with 5A8 in inhibiting infection
       by a patient HIV-1 isolate (0104B) and in blocking syncytium formation.
       These results indicate that therapeutics based on antibodies affecting
       both non-gp120 binding and gp120 binding epitopes of the target receptor
       molecule, CD4, could be efficient in patients who already contain
       anti-gp120 antibodies and could also be used to enhance passive
       immunization against HIV-1 in combination with anti-gp120 antibodies.
 DE    Acquired Immunodeficiency Syndrome/*THERAPY  Animal  Antibodies,
       Monoclonal/*THERAPEUTIC USE  Antigens, CD4/IMMUNOLOGY/*PHYSIOLOGY
       Binding Sites  Cell Fusion  Cell Line  Human  HIV Envelope Protein
       gp120/IMMUNOLOGY/*PHYSIOLOGY  HIV Envelope Protein gp41/PHYSIOLOGY
       HIV-1/*PHYSIOLOGY  Mice  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).