Blocking α4β7 integrin binding to SIV does not improve virologic control

Science. 2019 Sep 6;365(6457):1033-1036. doi: 10.1126/science.aaw7765.

Abstract

A study in nonhuman primates reported that infusions of an antibody against α4β7 integrin, in combination with antiretroviral therapy, showed consistent, durable control of simian immunodeficiency virus (SIV) in rhesus macaques. The antibody used has pleiotropic effects, so we set out to gain insight into the underlying mechanism by comparing this treatment to treatment with non-neutralizing monoclonal antibodies against the SIV envelope glycoprotein that only block α4β7 binding to SIV Env but have no other host-directed effects. Similar to the initial study, we used an attenuated strain of SIV containing a stop codon in nef. The study used 30 macaques that all began antiretroviral therapy and then were divided into five groups to receive different antibody treatments. Unlike the published report, we found no sustained virologic control by these treatments in vivo.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Viral / administration & dosage
  • Antibodies, Viral / therapeutic use*
  • DNA, Viral / blood
  • Gene Products, env / immunology
  • HIV Infections / therapy
  • Integrin alpha4 / immunology*
  • Integrin beta Chains / immunology*
  • Macaca mulatta
  • RNA, Viral / blood
  • 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
  • T-Lymphocytes / immunology
  • Viral Load
  • Viral Regulatory and Accessory Proteins / genetics
  • Viral Regulatory and Accessory Proteins / immunology
  • Virus Replication

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • DNA, Viral
  • Gene Products, env
  • Integrin beta Chains
  • NEF protein, SIV
  • RNA, Viral
  • Viral Regulatory and Accessory Proteins
  • integrin beta7
  • Integrin alpha4