title: HIV antibodies. Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies.
abstract: Some HIV-infected individuals develop broadly neutralizing antibodies (bNAbs), whereas most develop antibodies that neutralize only a narrow range of viruses (nNAbs). bNAbs, but not nNAbs, protect animals from experimental infection and are likely a key component of an effective vaccine. nNAbs and bNAbs target the same regions of the viral envelope glycoprotein (Env), but for reasons that remain unclear only nNAbs are elicited by Env immunization. We show that in contrast to germline-reverted (gl) bNAbs, glnNAbs recognized diverse recombinant Envs. Moreover, owing to binding affinity differences, nNAb B cell progenitors had an advantage in becoming activated and internalizing Env compared with bNAb B cell progenitors. We then identified an Env modification strategy that minimized the activation of nNAb B cells targeting epitopes that overlap those of bNAbs.
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: McGuire
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
authors.forename: Anita M
authors.initials: AM
authors.lastname: Dreyer
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Carbonetti
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Lippy
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
authors.forename: Jolene
authors.initials: J
authors.lastname: Glenn
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Scheid
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur and CNRS-URA 1961, 75015 Paris, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Mouquet
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109, USA.|Department of Global Health, University of Washington, Seattle, WA 98109, USA.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Stamatatos
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology; D001667:Binding, Competitive; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008958:Models, Molecular; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus