Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4-IgG. Academic Article uri icon

Overview

abstract

  • 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 impossible 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.

authors

  • Moore, John P
  • Trkola, Alexandra
  • Pomales, A B
  • Yuan, Hannah
  • Korber, Bette
  • Maddon, P J
  • Allaway, G P
  • Katinger, Hermann
  • Barbas, C F
  • Burton, D R
  • Ho, D D

publication date

  • November 1, 1995

Research

keywords

  • Acquired Immunodeficiency Syndrome
  • Antibodies, Monoclonal
  • Antigens, CD
  • CD4 Antigens
  • HIV Antibodies
  • HIV-1
  • Immunoglobulin G

Identity

PubMed Central ID

  • PMC189569

Scopus Document Identifier

  • 0028865465

Digital Object Identifier (DOI)

  • 10.1128/JVI.69.11.6609-6617.1995

PubMed ID

  • 7474069

Additional Document Info

volume

  • 69

issue

  • 11