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

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

Author information

1
Groupe d'Immunité des Muqueuses et Agents Pathogènes/EA3064, INSERM CIE3 1408 Vaccinology, Universités de Lyon, 42055 Saint-Etienne, France;
2
Université de Limoges, CNRS UMR 7276, 87032 Limoges, France;
3
Université Grenoble Alpes, Institut de Biologie Structurale, F-38044 Grenoble, France; Commissariat à l'Energie Atomique, Institut de Biologie Structurale, F-38044 Grenoble, France; CNRS, Institut de Biologie Structurale, F-38044 Grenoble, France;
4
Commissariat à l'Energie Atomique, Institut de Biologie Structurale, F-38044 Grenoble, France; Institut de Biologie et Chimie des Protéines, FRE3310/CNRS, Université de Lyon, F69007 Lyon, France; and.
5
B Cell Design, 87032 Limoges, France.
6
Groupe d'Immunité des Muqueuses et Agents Pathogènes/EA3064, INSERM CIE3 1408 Vaccinology, Universités de Lyon, 42055 Saint-Etienne, France; stephane.paul@chu-st-etienne.fr.

Abstract

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.

PMID:
27481846
DOI:
10.4049/jimmunol.1600309
[Indexed for MEDLINE]
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