Institutional members access full text with Ovid®

Share this article on:

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: May 1st, 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: stephane.paul@chu-st-etienne.fr).

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.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com).

Received December 02, 2016

Accepted January 23, 2017

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