Preliminary in vivo efficacy studies of a recombinant rhesus anti-α4β7 monoclonal antibody

• Type of Material: Article
• Authors: L. E. Pereira, Emory University; N. Onlamoon, Emory University; X. Wang, Beth Israel Deaconess Medical Center; R. Wang, Beth Israel Deaconess Medical Center; J. Li, Beth Israel Deaconess Medical Center; K. A. Reimann, Beth Israel Deaconess Medical Center; Francois Villinger, Emory University; K. Pattanapanyasat, Mahidol University; K. Mori, Natural Institute of Infectious Diseases; Aftab A Ansari, Emory University
• Language: English
• Date: 2009
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cellimm.2009.06.012
• Title of Journal or Parent Work: Cellular Immunology
• ISSN: 0008-8749
• Volume: 259
• Issue: 2
• Start Page: 165
• End Page: 176
• Grant/Funding Information: Supported by NIH RO1 AI 078773-01, N0I AI 040101, R24 RR016001, grants from the Thailand Research Fund and the Ministry of Health, Labor and Welfare, Japan.
• Keywords: antibodies; alpha4beta7 integrin; AIDS; Act1; Cell trafficking; T-cells; rhesus macaque
• Research Categories: Health Sciences, Pathology

Abstract

Recent findings established that primary targets of HIV/SIV are lymphoid cells within the gastrointestinal (GI) tract. Focus has therefore shifted to T-cells expressing α4β7 integrin which facilitates trafficking to the GI tract via binding to MAdCAM-1. Approaches to better understand the role of α4β7+ T-cells in HIV/SIV pathogenesis include their depletion or blockade of their synthesis, binding and/or homing capabilities in vivo. Such studies can ideally be conducted in rhesus macaques (RM), the non-human primate model of AIDS. Characterization of α4β7 expression on cell lineages in RM blood and GI tissues reveal low densities of expression by NK cells, B-cells, naïve and TEM (effector memory) T-cells. High densities were observed on TCM (central memory) T-cells. Intravenous administration of a single 50 mg/kg dose of recombinant rhesus α4β7 antibody resulted in significant initial decline of α4β7+ lymphocytes and sustained coating of the α4β7 receptor in both the periphery and GI tissues.