Research ArticleHIV

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

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Science Translational Medicine  18 Jan 2017:
Vol. 9, Issue 373, eaal2144
DOI: 10.1126/scitranslmed.aal2144

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Antibodies can hold HIV-1 at an impasse

Neutralizing antibodies put selective pressure on pathogens to mutate and escape from immune detection, which is one of the reasons why HIV-1 infection is difficult to contain. In this issue, Freund et al. studied samples spanning almost a decade from an individual who naturally controls HIV-1 infection without progressing to AIDS. They discovered three potent antibodies coexisting with viral strains that were sensitive to antibody neutralization, indicating that these antibodies may be contributing to viral control. These antibodies were also able to prevent HIV-1 viremia in humanized mice, demonstrating that the antibodies may be beneficial as passive immunotherapy for infected individuals.

Abstract

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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