Preliminary in vivo efficacy studies of a recombinant rhesus anti- alpha sub(4) beta sub(7) monoclonal antibody

• Published in: Cellular immunology Vol. 259; no. 2; pp. 165 - 176
• Main Authors: Pereira, LE, Onlamoon, N, Wang, X, Wang, R, Li, J, Reimann, KA, Villinger, F, Pattanapanyasat, K, Mori, K, Ansari, A A
• Format: Journal Article
• Language: English
• Published: 01.01.2009
• Subjects: Human immunodeficiency virus; Macaca mulatta; Primates; Simian immunodeficiency virus
• ISSN: 0008-8749
• DOI: 10.1016/j.cellimm.2009.06.012

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 alpha sub(4) beta sub(7) integrin which facilitates trafficking to the GI tract via binding to MAdCAM-1. Approaches to better understand the role of alpha sub(4) beta sub(7)+ 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 alpha sub(4) beta sub(7) expression on cell lineages in RM blood and GI tissues reveal low densities of expression by NK cells, B-cells, naive and TEM (effector memory) T-cells. High densities were observed on TCM (central memory) T-cells. Intravenous administration of a single 50mg/kg dose of recombinant rhesus alpha sub(4) beta sub(7) antibody resulted in significant initial decline of alpha sub(4) beta sub(7)+ lymphocytes and sustained coating of the alpha sub(4) beta sub(7) receptor in both the periphery and GI tissues.