Title | Coexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Freund NT, Wang H, Scharf L, Nogueira L, Horwitz JA, Bar-On Y, Golijanin J, Sievers SA, Sok D, Cai H, Lorenzi JCCesar, Halper-Stromberg A, Toth I, Piechocka-Trocha A, Gristick HB, van Gils MJ, Sanders RW, Wang L-X, Seaman MS, Burton DR, Gazumyan A, Walker BD, West AP, Bjorkman PJ, Nussenzweig MC |
Journal | Sci Transl Med |
Volume | 9 |
Issue | 373 |
Date Published | 2017 01 18 |
ISSN | 1946-6242 |
Keywords | Animals, Antibodies, Neutralizing, B-Lymphocytes, Cohort Studies, Crystallography, X-Ray, env Gene Products, Human Immunodeficiency Virus, Epitopes, HEK293 Cells, HIV Antibodies, HIV Infections, HIV-1, HLA-B Antigens, HLA-B27 Antigen, Humans, Mice, Mice, Transgenic, Neutralization Tests, Viral Load, Viremia |
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-infected humanized mice. Our finding suggests that combinations of bNAbs may contribute to control of HIV-1 infection. |
DOI | 10.1126/scitranslmed.aal2144 |
Alternate Journal | Sci Transl Med |
PubMed ID | 28100831 |
PubMed Central ID | PMC5467220 |
Grant List | P01 AI100148 / AI / NIAID NIH HHS / United States P50 GM082545 / GM / NIGMS NIH HHS / United States R01 AI113896 / AI / NIAID NIH HHS / United States UM1 AI100663 / AI / NIAID NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States |
Submitted by kej2006 on June 6, 2018 - 4:11pm