TY - JOUR
T1 - Coexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller
AU - Freund, Natalia T.
AU - Wang, Haoqing
AU - Scharf, Louise
AU - Nogueira, Lilian
AU - Horwitz, Joshua A.
AU - Bar-On, Yotam
AU - Golijanin, Jovana
AU - Sievers, Stuart A.
AU - Sok, Devin
AU - Cai, Hui
AU - Cesar Lorenzi, Julio C.
AU - Halper-Stromberg, Ariel
AU - Toth, Ildiko
AU - Piechocka-Trocha, Alicja
AU - Gristick, Harry B.
AU - van Gils, Marit J.
AU - Sanders, Rogier W.
AU - Wang, Lai-Xi
AU - Seaman, Michael S.
AU - Burton, Dennis R.
AU - Gazumyan, Anna
AU - Walker, Bruce D.
AU - West, Anthony P.
AU - Bjorkman, Pamela J.
AU - Nussenzweig, Michel C.
PY - 2017
Y1 - 2017
N2 - 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
AB - 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
U2 - https://doi.org/10.1126/scitranslmed.aal2144
DO - https://doi.org/10.1126/scitranslmed.aal2144
M3 - Article
C2 - 28100831
SN - 1946-6242
VL - 9
SP - eaal2144
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 373
ER -