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Sci Transl Med. 2017 Jan 18;9(373). pii: eaal2144. doi: 10.1126/scitranslmed.aal2144.

Coexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller.

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Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Department of Immunology and Microbial Science, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, and International AIDS Vaccine Initiative Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Chemistry and Biochemistry, University of Maryland, 8051 Regents Drive, College Park, MD 20742, USA.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02129, USA.
Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.


Some HIV-1-infected patients develop broad and potent HIV-1 neutralizing antibodies (bNAbs) that when passively transferred to mice or macaques can treat or prevent infection. However, bNAbs typically fail to neutralize coexisting autologous viruses due to antibody-mediated selection against sensitive viral strains. We describe an HIV-1 controller expressing HLA-B57*01 and HLA-B27*05 who maintained low viral loads for 30 years after infection and developed broad and potent serologic activity against HIV-1. Neutralization was attributed to three different bNAbs targeting nonoverlapping sites on the HIV-1 envelope trimer (Env). One of the three, BG18, an antibody directed against the glycan-V3 portion of Env, is the most potent member of this class reported to date and, as revealed by crystallography and electron microscopy, recognizes HIV-1 Env in a manner that is distinct from other bNAbs in this class. Single-genome sequencing of HIV-1 from serum samples obtained over a period of 9 years showed a diverse group of circulating viruses, 88.5% (31 of 35) of which remained sensitive to at least one of the temporally coincident autologous bNAbs and the individual's serum. Thus, bNAb-sensitive strains of HIV-1 coexist with potent neutralizing antibodies that target the virus and may contribute to control in this individual. When administered as a mix, the three bNAbs controlled viremia in HIV-1YU2-infected humanized mice. Our finding suggests that combinations of bNAbs may contribute to control of HIV-1 infection.

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