First Membrane Proximal External Region-Specific Anti-HIV1 Broadly Neutralizing Monoclonal IgA1 Presenting Short CDRH3 and Low Somatic Mutations

J Immunol. 2016 Sep 1;197(5):1979-88. doi: 10.4049/jimmunol.1600309. Epub 2016 Aug 1.


Mucosal HIV-1-specific IgA have been described as being able to neutralize HIV-1 and to block viral transcytosis. In serum and saliva, the anti-HIV IgA response is predominantly raised against the envelope of HIV-1. In this work, we describe the in vivo generation of gp41-specific IgA1 in humanized α1KI mice to produce chimeric IgA1. Mice were immunized with a conformational immunogenic gp41-transfected cell line. Among 2300 clones screened by immunofluorescence microscopy, six different gp41-specific IgA with strong recognition of gp41 were identified. Two of them have strong neutralizing activity against primary HIV-1 tier 1, 2, and 3 strains and present a low rate of somatic mutations and autoreactivity, unlike what was described for classical gp41-specific IgG. Epitopes were identified and located in the hepted repeat 2/membrane proximal external region. These Abs could be of interest in prophylactic treatment to block HIV-1 penetration in mucosa or in chronically infected patients in combination with antiretroviral therapy to reduce viral load and reservoir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / isolation & purification
  • Epitopes / genetics
  • Epitopes / immunology
  • Fluorescent Antibody Technique
  • HIV Antibodies / chemistry
  • HIV Antibodies / immunology*
  • HIV Envelope Protein gp41 / immunology*
  • HIV-1 / immunology*
  • Immunoglobulin A / chemistry*
  • Immunoglobulin A / genetics
  • Immunoglobulin A / immunology*
  • Immunoglobulin A / isolation & purification
  • Mice
  • Mice, Transgenic
  • Mucous Membrane / immunology
  • Mutation
  • Recombinant Proteins / immunology
  • Recombinant Proteins / isolation & purification


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp41
  • Immunoglobulin A
  • Recombinant Proteins