HIV therapy by a combination of broadly neutralizing antibodies in humanized mice

Nature. 2012 Dec 6;492(7427):118-22. doi: 10.1038/nature11604. Epub 2012 Oct 24.

Abstract

Human antibodies to human immunodeficiency virus-1 (HIV-1) can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice. Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy, the longer half-life of antibodies led to control of viraemia for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in humanized mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / therapeutic use*
  • Antibody Specificity / immunology
  • Disease Models, Animal
  • HIV Antibodies / immunology*
  • HIV Antibodies / therapeutic use*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / growth & development
  • HIV-1 / immunology
  • HIV-1 / isolation & purification
  • Half-Life
  • Humans
  • Immunization, Passive
  • Mice
  • Mice, Inbred NOD
  • Time Factors
  • Viral Load / drug effects

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • HIV Antibodies