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

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.