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

Ching Lan Lu, Dariusz K. Murakowski, Stylianos Bournazos, Till Schoofs, Debolina Sarkar, Ariel Halper-Stromberg, Joshua A. Horwitz, Lilian Nogueira, Jovana Golijanin, Anna Gazumyan, Jeffrey V. Ravetch, Marina Caskey, Arup K. Chakraborty, Michel C. Nussenzweig

Research output: Contribution to journalArticlepeer-review

233 Scopus citations

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.

Original languageEnglish
Pages (from-to)1001-1004
Number of pages4
JournalScience
Volume352
Issue number6288
DOIs
StatePublished - 20 May 2016
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by Collaboration for AIDS Vaccine Discovery grant OPP1033115 (M.C.N. and J.V.R.). This work was also supported, in part, by grant 8 UL1 TR000043 from the National Center for Advancing Translational Sciences (NCATS); NIH Clinical and Translational Science Award (CTSA) program; NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) 1UM1 AI100663-01 (M.C.N); Bill and Melinda Gates Foundation grants OPP1092074 and OPP1124068 (M.C.N); the Robertson Foundation to M.C.N.; German Research Foundation postdoctoral fellowship SCHO 1612/1-1 (T.S.); NIH grant F31 AI118555-01 (J.A.H.); the American Foundation for AIDS research (amfAR) Mathilde Krim Fellowship in Basic Biomedical Research (108977-57-RKVA) (S.B.); the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute ofTechnology, and Harvard (A.K.C.); a NSF Graduate Research Fellowship under grant no. 1122374 (D.K.M.); and National Institute of Allergy and Infectious Diseases (NIH) grants AI100148-02 and AI081677-05 (M.C.N. and J.V.R.).

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