Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo

Science. 2016 May 20;352(6288):1001-4. doi: 10.1126/science.aaf1279. Epub 2016 May 5.

Abstract

Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-1-infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection but also include acceleration of infected cell clearance. Consistent with these observations, we find that broadly neutralizing antibodies can target CD4(+) T cells infected with patient viruses and can decrease their in vivo half-lives by a mechanism that requires Fcγ receptor engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1-infected cells.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing / immunology*
  • Apoptosis / immunology
  • Broadly Neutralizing Antibodies
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Line
  • HIV Antibodies / immunology*
  • HIV Infections / therapy*
  • HIV Infections / virology*
  • HIV-1 / immunology*
  • Homeodomain Proteins / genetics
  • Humans
  • Immunization, Passive
  • Immunosuppression Therapy
  • Interleukin Receptor Common gamma Subunit / genetics
  • Mice
  • Mice, Inbred NOD
  • Mice, Mutant Strains
  • Receptors, IgG / immunology
  • Viral Load / immunology*

Substances

  • 3BNC117 antibody
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • HIV Antibodies
  • Homeodomain Proteins
  • Il2rg protein, mouse
  • Interleukin Receptor Common gamma Subunit
  • Receptors, IgG
  • RAG-1 protein