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Neutralizing and Targeting Properties of a New Set of α4β7-Specific Antibodies Are Influenced by Their Isotype

Girard, Alexandre PhD*; Jelicic, Katija PhD; Van Ryk, Don PhD; Rochereau, Nicolas PhD*; Cicala, Claudia PhD; Arthos, James PhD; Noailly, Blandine*; Genin, Christian PhD*; Verrier, Bernard PhD; Laurant, Stephanie MSc§; Razanajaoana-Doll, Diane PhD§; Pin, Jean-Jacques PhD§; Paul, Stéphane PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: 01 May 2017 - Volume 75 - Issue 1 - p 118–127
doi: 10.1097/QAI.0000000000001307
Basic Science

Abstract: The homing of lymphocytes to the mucosa is mainly controlled by α4β7 integrin, and it is amplified during gut chronic inflammation, as occurs with HIV and/or inflammatory bowel diseases. We designed and applied an improved immunization strategy based on an innovative selection process to isolate new α4β7+ lymphocyte–specific monoclonal antibodies that are able to prevent their migration into inflamed gut tissues and/or to counteract HIV infection in vitro. First, 5 monoclonal antibodies (1 IgA, 1 IgM, and 4 IgGs) were selected based on their capacity to recognize α4 or β7 homodimers and α4β7 heterodimers in transfected human cells. Their ability to block gp120/α4β7 or MAdCAM-1/α4β7 interactions was then measured in vitro with human T and B lymphocytes. In vitro, the anti-α4β7 IgA isotype was found to have the highest affinity for the α4β7 heterodimer, and it significantly reduced HIV replication in retinoic acid–treated α4β7hi CD4+ human T cells. This α4β7-specific IgA also displayed a high avidity for human and mouse α4β7+ lymphocytes in both mouse and human inflammatory colitis tissues. These new antibodies, and in particular those with mucosa-targeting isotypes such as IgA, could therefore be potential novel therapeutic tools for treating HIV and inflammatory bowel disease.

*GIMAP/EA3064, Université de Lyon, Saint-Etienne, France;

NIH/NIAID Laboratory of Immunoregulation, Bethesda, MD;

Institut de Biologie et Chimie des Protéines, FRE3310/CNRS, Universités de Lyon, Lyon, France; and

§Dendritics SA, Lyon, France.

Correspondence to: Stéphane Paul, PhD, GIMAP EA3064, CIC1408, Laboratoire d'Immunologie CHU Saint-Etienne, Universités de Lyon, Saint-Etienne, France (e-mail:

A.G. was supported by a doctoral fellowship from Region Rhone-Alpes (France). This work was financed by research grants from Region Rhone-Alpes, ANRS, and Sidaction.

The authors have no conflicts of interest to disclose.

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Received December 02, 2016

Accepted January 23, 2017

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.