A monoclonal Fab derived from a human nonimmune phage library reveals a new epitope on gp41 and neutralizes diverse human immunodeficiency virus type 1 strains

J Virol. 2007 Dec;81(23):12946-53. doi: 10.1128/JVI.01260-07. Epub 2007 Sep 26.


A monoclonal Fab (Fab 3674) selected from a human nonimmune phage library by panning against the chimeric construct N(CCG)-gp41 (which comprises an exposed coiled-coil trimer of gp41 N helices fused in the helical phase onto the minimal thermostable ectodomain of gp41) is described. Fab 3674 is shown to neutralize diverse laboratory-adapted B strains of human immunodeficiency virus type 1 (HIV-1) and primary isolates of subtypes A, B, and C in an Env-pseudotyped-virus neutralization assay, albeit with reduced potency (approximately 25-fold) compared to that of 2F5 and 4E10. Alanine scanning mutagenesis maps a novel epitope to a shallow groove on the N helices of gp41 that is exposed between two C helices in the fusogenic six-helix bundle conformation of gp41. Bivalent Fab 3674 and the C34 peptide (a potent fusion inhibitor derived from the C helix of gp41) are shown to act at similar stages of the fusion reaction and to neutralize HIV-1 synergistically, providing additional evidence that the epitope of Fab 3674 is new and distinct from the binding site of C34.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Substitution / genetics
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Viral / immunology*
  • Cell Line
  • Epitope Mapping
  • Epitopes / immunology*
  • Gene Library
  • HIV Envelope Protein gp41 / immunology*
  • HIV-1 / immunology*
  • Humans
  • Immunoglobulin Fab Fragments / genetics*
  • Immunoglobulin Fab Fragments / immunology*
  • Mutagenesis, Site-Directed
  • Neutralization Tests


  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Epitopes
  • HIV Envelope Protein gp41
  • Immunoglobulin Fab Fragments
  • gp41 protein, Human immunodeficiency virus 1