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

Natalia T. Freund, Haoqing Wang, Louise Scharf, Lilian Nogueira, Joshua A. Horwitz, Yotam Bar-On, Jovana Golijanin, Stuart A. Sievers, Devin Sok, Hui Cai, Julio C.Cesar Lorenzi, Ariel Halper-Stromberg, Ildiko Toth, Alicja Piechocka-Trocha, Harry B. Gristick, Marit J. Van Gils, Rogier W. Sanders, Lai Xi Wang, Michael S. Seaman, Dennis R. BurtonAnna Gazumyan, Bruce D. Walker, Anthony P. West, Pamela J. Bjorkman, Michel C. Nussenzweig

Research output: Contribution to journalArticlepeer-review

Abstract

Some HIV-1-infected patients develop broad and potent HIV-1 neutralizing antibodies (bNAbs) that when passively transferred to mice ormacaques 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) ofwhich remained sensitive to at least one of the temporally coincident autologous bNAbs and the individual's serum. Thus, bNAb-sensitive strains of HIV-1 coexistwith 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.

Original languageEnglish
Article numbereaal2144
JournalScience Translational Medicine
Volume9
Issue number373
DOIs
StatePublished - 18 Jan 2017
Externally publishedYes

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