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Open Access Publications from the University of California

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

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

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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-1YU2-infected humanized mice. Our finding suggests that combinations of bNAbs may contribute to control of HIV-1 infection.

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