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

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

Natalia T Freund  1 , Haoqing Wang  2 , Louise Scharf  2 , Lilian Nogueira  1 , Joshua A Horwitz  1 , Yotam Bar-On  1 , Jovana Golijanin  1 , Stuart A Sievers  2 , Devin Sok  3 , Hui Cai  4 , Julio C Cesar Lorenzi  1 , Ariel Halper-Stromberg  1 , Ildiko Toth  5 , Alicja Piechocka-Trocha  5 , Harry B Gristick  2 , Marit J van Gils  6 , Rogier W Sanders  6 , Lai-Xi Wang  4 , Michael S Seaman  7 , Dennis R Burton  3   5 , Anna Gazumyan  1 , Bruce D Walker  5   8 , Anthony P West Jr  2 , Pamela J Bjorkman  2 , Michel C Nussenzweig  9   8
Affiliations

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

Natalia T Freund et al. Sci Transl Med. .

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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Figures

Figure 1
Figure 1
Neutralizing antibodies isolated from donor EB354.
Figure 2
Figure 2
Sequence and structural analysis of BG18 bNAb.
Figure 3
Figure 3
Autologous plasma viruses in donor EB354.
Figure 4
Figure 4
bNAb therapy in HIV YU2-infected humanized mice.
See this image and copyright information in PMC

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