Download MendeleyCoexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller.
Freund, N.T., Wang, H., Scharf, L., Nogueira, L., Horwitz, J.A., Bar-On, Y., Golijanin, J., Sievers, S.A., Sok, D., Cai, H., Cesar Lorenzi, J.C., Halper-Stromberg, A., Toth, I., Piechocka-Trocha, A., Gristick, H.B., van Gils, M.J., Sanders, R.W., Wang, L.X., Seaman, M.S., Burton, D.R., Gazumyan, A., Walker, B.D., West, A.P., Bjorkman, P.J., Nussenzweig, M.C.(2017) Sci Transl Med 9
- PubMed: 28100831
- DOI: https://doi.org/10.1126/scitranslmed.aal2144
- Primary Citation of Related Structures:
5UD9, 5UEL - PubMed 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-1 YU2 -infected humanized mice. Our finding suggests that combinations of bNAbs may contribute to control of HIV-1 infection.
Organizational Affiliation:
Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.
