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

Cell Immunol. 2009;259(2):165-76. doi: 10.1016/j.cellimm.2009.06.012. Epub 2009 Jun 26.


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(4)beta(7) integrin which facilitates trafficking to the GI tract via binding to MAdCAM-1. Approaches to better understand the role of alpha(4)beta(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(4)beta(7) 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 50mg/kg dose of recombinant rhesus alpha(4)beta(7) antibody resulted in significant initial decline of alpha(4)beta(7)+ lymphocytes and sustained coating of the alpha(4)beta(7) receptor in both the periphery and GI tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / pharmacology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Cross-Sectional Studies
  • Flow Cytometry
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / immunology
  • Gastrointestinal Tract / virology
  • Integrins / biosynthesis
  • Integrins / immunology*
  • Longitudinal Studies
  • Macaca mulatta
  • Male
  • Pilot Projects
  • RNA, Viral / chemistry
  • RNA, Viral / genetics
  • Recombinant Proteins / blood
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Simian Acquired Immunodeficiency Syndrome / blood
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / virology
  • Tretinoin / pharmacology
  • Viral Load


  • Antibodies, Monoclonal
  • Integrins
  • RNA, Viral
  • Recombinant Proteins
  • integrin alpha4beta7
  • Tretinoin