Lack of therapeutic efficacy of an antibody to α 4 β 7 in SIVmac251-infected rhesus macaques

Science. 2019 Sep 6;365(6457):1029-1033. doi: 10.1126/science.aaw8562. Epub 2019 Sep 5.

Abstract

Sustained virologic control of human immunodeficiency virus type 1 (HIV-1) infection after discontinuation of antiretroviral therapy (ART) is a major goal of the HIV-1 cure field. A recent study reported that administration of an antibody against α4β7 induced durable virologic control after ART discontinuation in 100% of rhesus macaques infected with an attenuated strain of simian immunodeficiency virus (SIV) containing a stop codon in nef We performed similar studies in 50 rhesus macaques infected with wild-type, pathogenic SIVmac251. In animals that initiated ART during either acute or chronic infection, anti-α4β7 antibody infusion had no detectable effect on the viral reservoir or viral rebound after ART discontinuation. These data demonstrate that anti-α4β7 antibody administration did not provide therapeutic efficacy in the model of pathogenic SIVmac251 infection of rhesus macaques.

Publication types

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

MeSH terms

  • Animals
  • Anti-Retroviral Agents / therapeutic use
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Viral / administration & dosage
  • Antibodies, Viral / therapeutic use*
  • Codon, Terminator
  • DNA, Viral / blood
  • HIV Infections / therapy
  • Integrin alpha4 / immunology*
  • Integrin beta Chains / immunology*
  • Macaca mulatta
  • Simian Acquired Immunodeficiency Syndrome / blood
  • Simian Acquired Immunodeficiency Syndrome / drug therapy
  • Simian Acquired Immunodeficiency Syndrome / therapy*
  • Simian Acquired Immunodeficiency Syndrome / virology*
  • Simian Immunodeficiency Virus / genetics*
  • Simian Immunodeficiency Virus / immunology*
  • Simian Immunodeficiency Virus / physiology
  • Viral Load
  • Viral Regulatory and Accessory Proteins / genetics
  • Viral Regulatory and Accessory Proteins / immunology

Substances

  • Anti-Retroviral Agents
  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Codon, Terminator
  • DNA, Viral
  • Integrin beta Chains
  • NEF protein, SIV
  • Viral Regulatory and Accessory Proteins
  • integrin beta7
  • Integrin alpha4