title: Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide.
abstract: A goal for an HIV-1 vaccine is to overcome virus variability by inducing broadly neutralizing antibodies (bnAbs). One key target of bnAbs is the glycan-polypeptide at the base of the envelope (Env) third variable loop (V3). We have designed and synthesized a homogeneous minimal immunogen with high-mannose glycans reflective of a native Env V3-glycan bnAb epitope (Man9-V3). V3-glycan bnAbs bound to Man9-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man9-V3 glycopeptides bound to bnAb memory B cells and were able to be used to isolate a V3-glycan bnAb from an HIV-1-infected individual. In rhesus macaques, immunization with Man9-V3 induced V3-glycan-targeted antibodies. Thus, the Man9-V3 glycopeptide closely mimics an HIV-1 V3-glycan bnAb epitope and can be used to isolate V3-glycan bnAbs.
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.|Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: S Munir
authors.identifier: 0000-0003-0941-0703
authors.initials: SM
authors.lastname: Alam
authors.affiliation: Department of Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Baptiste
authors.identifier: 0000-0002-8828-8963
authors.initials: B
authors.lastname: Aussedat
authors.affiliation: Department of Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Yusuf
authors.identifier: 0000-0003-0385-2965
authors.initials: Y
authors.lastname: Vohra
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.|Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: R Ryan
authors.identifier: 0000-0003-1253-2250
authors.initials: RR
authors.lastname: Meyerhoff
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Evan M
authors.identifier: 0000-0002-9176-8263
authors.initials: EM
authors.lastname: Cale
authors.affiliation: Department of Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: William E
authors.identifier: 0000-0002-7961-1175
authors.initials: WE
authors.lastname: Walkowicz
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Radakovich
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Kara
authors.identifier: 0000-0002-1854-743X
authors.initials: K
authors.lastname: Anasti
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Armand
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Parks
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Laura
authors.identifier: 0000-0003-4119-3884
authors.initials: L
authors.lastname: Sutherland
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Scearce
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: M Gordon
authors.identifier: 0000-0002-6808-7232
authors.initials: MG
authors.lastname: Joyce
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Pancera
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Aliaksandr
authors.initials: A
authors.lastname: Druz
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ivelin S
authors.initials: IS
authors.lastname: Georgiev
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Tarra
authors.identifier: 0000-0001-8690-9095
authors.initials: T
authors.lastname: Von Holle
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Amanda
authors.identifier: 0000-0003-3064-2947
authors.initials: A
authors.lastname: Eaton
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Fox
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Steven G
authors.identifier: 0000-0003-2193-100X
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Mark
authors.identifier: 0000-0001-7540-9263
authors.initials: M
authors.lastname: Louder
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.affiliation: National Institute for Communicable Diseases, Johannesburg 2131, South Africa.|Center for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban 4013, South Africa.
authors.forename: Lynn
authors.identifier: 0000-0003-3961-7828
authors.initials: L
authors.lastname: Morris
authors.affiliation: National Institute for Communicable Diseases, Johannesburg 2131, South Africa.|Center for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban 4013, South Africa.
authors.forename: Salim S
authors.identifier: 0000-0002-4986-2133
authors.initials: SS
authors.lastname: Abdool-Karim
authors.affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Myron
authors.identifier: 0000-0001-5917-9664
authors.initials: M
authors.lastname: Cohen
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.|Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Department of Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
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authors.initials: PK
authors.lastname: Park
authors.affiliation: Department of Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Alberto
authors.identifier: 0000-0002-1680-0059
authors.initials: A
authors.lastname: Fernández-Tejada
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Kevin
authors.initials: K
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authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
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authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Thomas B
authors.identifier: 0000-0002-1383-6865
authors.initials: TB
authors.lastname: Kepler
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.|Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
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authors.initials: KO
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authors.forename: Joseph
authors.identifier: 0000-0002-9750-1615
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authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Peter D
authors.identifier: 0000-0003-3560-232X
authors.initials: PD
authors.lastname: Kwong
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Mattia
authors.identifier: 0000-0003-2973-2101
authors.initials: M
authors.lastname: Bonsignori
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.|Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.|Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: M Anthony
authors.identifier: 0000-0002-3890-5855
authors.initials: MA
authors.lastname: Moody
authors.affiliation: Department of Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Danishefsky
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.|Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Barton F
authors.identifier: 0000-0002-2847-1854
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D000918:Antibody Specificity / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology; D019070:Cell Lineage; D002469:Cell Separation; D002999:Clone Cells; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006020:Glycopeptides / Q000737:chemistry / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D008253:Macaca mulatta; D018716:Molecular Mimicry / Q000276:immunology*; D000072417:Protein Domains; D055503:Protein Multimerization
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D006020:Glycopeptides; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120