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 language | English |
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Pages (from-to) | 1001-1004 |
Number of pages | 4 |
Journal | Science |
Volume | 352 |
Issue number | 6288 |
DOIs | |
State | Published - 20 May 2016 |
Externally published | Yes |
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.).
Funding
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.).
Funders | Funder number |
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American Foundation for AIDS research | 108977-57-RKVA |
Collaboration for AIDS Vaccine Discovery | 8 UL1 TR000043, OPP1033115 |
Massachusetts Institute ofTechnology, and Harvard | |
Ragon Institute of Massachusetts General Hospital | |
National Science Foundation | 1122374 |
National Institutes of Health | |
National Institute of Allergy and Infectious Diseases | AI100148-02, UM1AI100663, AI081677-05 |
Bill and Melinda Gates Foundation | OPP1124068, OPP1092074 |
National Center for Advancing Translational Sciences | |
Robertson Foundation | |
Deutsche Forschungsgemeinschaft | F31 AI118555-01, SCHO 1612/1-1 |