Characterization of an anti-lymphocyte function-associated antigen-1 antibody in a simian immunodeficiency virus-pig-tailed macaque (Macaca nemestrina) model

Craig A. Fletcher, Zhaohao Liao, Robert J. Adams, Darryl L. Carter, Odell D. Jones, Harry G. Davis, Joseph L. Bryant, James E.K. Hildreth

Research output: Contribution to journalArticle

Abstract

The simian immunodeficiency virus (SIV)/pig-tailed macaque (Macaca nemestrina) model of acquired immune deficiency syndrome (AIDS) is a powerful system in which to study cell adhesion molecules and retroviral pathogenesis in vivo. Preliminary experiments were conducted to examine the role of lymphocyte function-associated antigen 1 (LFA-1) in early SIV infection in vivo by using an LFA-1 monoclonal antibody (MHM.23) specific to human LFA-1. In vitro studies revealed that at concentrations of ≥20 μg/ml, MHM.23 blocked LFA-1-mediated adhesion and T-cell activation (>90%) of pig-tailed macaque peripheral blood mononuclear cells (PBMCs). In addition, SIVmac239 infection of macaque cells was inhibited in a dose-dependant manner by MHM.23. Administration of MHM.23 to pig-tailed macaques inhibited LFA-1-ICAM-1-mediated activity in vivo and maintained binding on macaque cells for ≤4 d. Our in vitro studies indicated that at an MHM.23 concentration of 20 μg/ml, macaque PBMCs were completely saturated. Our in vivo studies determined that 5 mg/kg MHM.23 intravenously every 24 h was required to maintain saturating levels and inhibit LFA-1-ICAM-1 function in pig-tailed macaques.

Original languageEnglish (US)
Pages (from-to)23-30
Number of pages8
JournalComparative medicine
Volume56
Issue number1
StatePublished - Feb 1 2006

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • veterinary(all)

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