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

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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.
Funding Information
  • Collaboration for AIDS Vaccine Discovery (OPP1033115)
  • National Center for Advancing Translational Sciences (NCATS) (UL1 TR000043)
  • NIH Clinical and Translational Science Award (CTSA)
  • NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) (1UM1 AI100663-01)
  • Bill and Melinda Gates Foundation (OPP1092074, OPP1124068)
  • Robertson Foundation
  • German Research Foundation (SCHO 1612/1-1)
  • NIH (F31 AI118555-01)
  • American Foundation for AIDS research (amfAR) Mathilde Krim Fellowship in Basic Biomedical Research (108977-57-RKVA)
  • Ragon Institute of Massachusetts General Hospital
  • Massachusetts Institute of Technology
  • NSF Graduate Research Fellowship (1122374)
  • National Institute of Allergy and Infectious Diseases (AI100148-02, AI081677-05)