- 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
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.