       Document 0413
 DOCN  M9620413
 TI    Cross-clade neutralization of primary isolates of human immunodeficiency
       virus type 1 by human monoclonal antibodies and tetrameric CD4-IgG.
 DT    9602
 AU    Trkola A; Pomales AB; Yuan H; Korber B; Maddon PJ; Allaway GP; Katinger
       H; Barbas CF 3rd; Burton DR; Ho DD; et al; Aaron Diamond AIDS Research
       Center, New York University School of; Medicine, New York 10016, USA.
 SO    J Virol. 1995 Nov;69(11):6609-17. Unique Identifier : AIDSLINE
       MED/96013752
 AB    We have tested three human monoclonal antibodies (MAbs) IgG1b12, 2G12,
       and 2F5) to the envelope glycoproteins of human immunodeficiency virus
       type 1 (HIV-1), and a tetrameric CD4-IgG molecule (CD4-IgG2), for the
       ability to neutralize primary HIV-1 isolates from the genetic clades A
       through F and from group O. Each of the reagents broadly and potently
       neutralized B-clade isolates. The 2F5 MAb and the CD4-IgG2 molecule also
       neutralized strains from outside the B clade, with the same breadth and
       potency that they showed against B-clade strains. The other two MAbs
       were able to neutralize a significant proportion of strains from outside
       the B clade, although there was a reduction in their efficacy compared
       with their activity against B-clade isolates. Neutralization of isolates
       by 2F5 correlated with their possession of the LDKW motif in a segment
       of gp41 near the membrane-spanning domain. The other two MAbs and
       CD4-IgG2 recognize discontinuous binding sites on gp120, and so no
       comparison between genetic sequence and virus neutralization was
       possible. Our data show that a vaccine based on the induction of humoral
       immunity that is broadly active across the genetic clades is not
       possible if immunogens that express the epitopes for MAbs such as 2F5,
       2G12, and IgG1b12 in immunogenic configurations can be created.
       Furthermore, if the three MAbs and CD4-IgG2 produce clinical benefit in
       immunotherapeutic trials in the United States or Europe, they may also
       do so elsewhere in the world.
 DE    Acquired Immunodeficiency Syndrome/*IMMUNOLOGY  Amino Acid Sequence
       Antibodies, Monoclonal/*IMMUNOLOGY  Antigen-Antibody Complex  Antigens,
       CD/*IMMUNOLOGY  Antigens, CD4/*IMMUNOLOGY  Comparative Study
       Epitopes/ANALYSIS/CHEMISTRY/IMMUNOLOGY  Human  HIV
       Antibodies/*IMMUNOLOGY  HIV Envelope Protein gp120/IMMUNOLOGY
       HIV-1/CLASSIFICATION/*IMMUNOLOGY/ISOLATION & PURIF
       IgG/CLASSIFICATION/*IMMUNOLOGY  Immunoglobulins, Fab/IMMUNOLOGY
       Molecular Sequence Data  Neutralization Tests  Recombinant
       Proteins/IMMUNOLOGY  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).

