title: First Membrane Proximal External Region-Specific Anti-HIV1 Broadly Neutralizing Monoclonal IgA1 Presenting Short CDRH3 and Low Somatic Mutations.
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.
authors.affiliation: Groupe d'Immunité des Muqueuses et Agents Pathogènes/EA3064, INSERM CIE3 1408 Vaccinology, Universités de Lyon, 42055 Saint-Etienne, France;
authors.forename: Fahd
authors.identifier: 0000-0001-6939-8721
authors.initials: F
authors.lastname: Benjelloun
authors.affiliation: Université de Limoges, CNRS UMR 7276, 87032 Limoges, France;
authors.forename: Zeliha
authors.identifier: 0000-0003-1314-6757
authors.initials: Z
authors.lastname: Oruc
authors.affiliation: 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;
authors.forename: Nicole
authors.identifier: 0000-0002-7354-0302
authors.initials: N
authors.lastname: Thielens
authors.affiliation: 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.
authors.forename: Bernard
authors.identifier: 0000-0002-8478-7095
authors.initials: B
authors.lastname: Verrier
authors.affiliation: B Cell Design, 87032 Limoges, France.
authors.forename: Gael
authors.identifier: 0000-0002-0089-9357
authors.initials: G
authors.lastname: Champier
authors.affiliation: Groupe d'Immunité des Muqueuses et Agents Pathogènes/EA3064, INSERM CIE3 1408 Vaccinology, Universités de Lyon, 42055 Saint-Etienne, France;
authors.forename: Nadine
authors.initials: N
authors.lastname: Vincent
authors.affiliation: Groupe d'Immunité des Muqueuses et Agents Pathogènes/EA3064, INSERM CIE3 1408 Vaccinology, Universités de Lyon, 42055 Saint-Etienne, France;
authors.forename: Nicolas
authors.identifier: 0000-0001-6579-0275
authors.initials: N
authors.lastname: Rochereau
authors.affiliation: Groupe d'Immunité des Muqueuses et Agents Pathogènes/EA3064, INSERM CIE3 1408 Vaccinology, Universités de Lyon, 42055 Saint-Etienne, France;
authors.forename: Alexandre
authors.identifier: 0000-0002-7251-8779
authors.initials: A
authors.lastname: Girard
authors.affiliation: Groupe d'Immunité des Muqueuses et Agents Pathogènes/EA3064, INSERM CIE3 1408 Vaccinology, Universités de Lyon, 42055 Saint-Etienne, France;
authors.forename: Fabienne
authors.initials: F
authors.lastname: Jospin
authors.affiliation: Groupe d'Immunité des Muqueuses et Agents Pathogènes/EA3064, INSERM CIE3 1408 Vaccinology, Universités de Lyon, 42055 Saint-Etienne, France;
authors.forename: Blandine
authors.identifier: 0000-0001-7841-4973
authors.initials: B
authors.lastname: Chanut
authors.affiliation: Groupe d'Immunité des Muqueuses et Agents Pathogènes/EA3064, INSERM CIE3 1408 Vaccinology, Universités de Lyon, 42055 Saint-Etienne, France;
authors.forename: Christian
authors.identifier: 0000-0003-2065-8267
authors.initials: C
authors.lastname: Genin
authors.affiliation: Université de Limoges, CNRS UMR 7276, 87032 Limoges, France;
authors.forename: Michel
authors.identifier: 0000-0002-8519-4427
authors.initials: M
authors.lastname: Cogné
authors.affiliation: 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.
authors.forename: Stephane
authors.identifier: 0000-0002-8830-4273
authors.initials: S
authors.lastname: Paul
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000302:isolation & purification; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005455:Fluorescent Antibody Technique; D015483:HIV Antibodies / Q000737:chemistry / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007070:Immunoglobulin A / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D051379:Mice; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000276:immunology; D009154:Mutation; D011994:Recombinant Proteins / Q000276:immunology / Q000302:isolation & purification
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D007070:Immunoglobulin A; D011994:Recombinant Proteins