Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 9, Issue 373, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aal2144
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Funding
- Robertson Foundation
- Rockefeller University
- Bill and Melinda Gates Foundation [OPP1033115]
- Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Scripps grant [UM1 AI 100663]
- NIH HIV Vaccine Research and Design grant [1 P01 AI100148]
- NIH [2 P50 GM082545-06]
- Gordon and Betty Moore Foundation
- Melinda and Bill Gates Foundation [OPP1032144]
- California HIV/AIDS Research Program (CHRP) [F12-CT-214]
- Bill and Melinda Gates Foundation [OPP1033115] Funding Source: Bill and Melinda Gates Foundation
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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-1(YU2)-infected humanized mice. Our finding suggests that combinations of bNAbs may contribute to control of HIV-1 infection.
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