title: Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates.
abstract: Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans-a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors.
authors.affiliation: Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: kevin.saunders@dm.duke.edu.
authors.forename: Kevin O
authors.initials: KO
authors.lastname: Saunders
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Nathan I
authors.initials: NI
authors.lastname: Nicely
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Wiehe
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Mattia
authors.initials: M
authors.lastname: Bonsignori
authors.affiliation: Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: R Ryan
authors.initials: RR
authors.lastname: Meyerhoff
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Parks
authors.affiliation: Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Walkowicz
authors.affiliation: Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Aussedat
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Nelson R
authors.initials: NR
authors.lastname: Wu
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Fangping
authors.initials: F
authors.lastname: Cai
authors.affiliation: Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Vohra
authors.affiliation: Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Park
authors.affiliation: Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Eaton
authors.affiliation: University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Eden P
authors.initials: EP
authors.lastname: Go
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Sutherland
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Scearce
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Ruijun
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Tarra
authors.initials: T
authors.lastname: Von Holle
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: R Glenn
authors.initials: RG
authors.lastname: Overman
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Anasti
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Rogier W
authors.initials: RW
authors.lastname: Sanders
authors.affiliation: Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
authors.affiliation: Boston University, Boston, MA 02215, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kepler
authors.affiliation: LANL, Los Alamos, NM 87545, USA.
authors.forename: Bette
authors.initials: B
authors.lastname: Korber
authors.affiliation: University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Desaire
authors.affiliation: Harvard Medical School, Boston, MA, 02215, USA.
authors.forename: Sampa
authors.initials: S
authors.lastname: Santra
authors.affiliation: Harvard Medical School, Boston, MA, 02215, USA.
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.affiliation: Sanofi, Cambridge, MA 02139, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.affiliation: 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 Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.affiliation: Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Danishefsky
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: barton.haynes@duke.edu.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001665:Binding Sites / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D008253:Macaca mulatta; D008358:Mannose / Q000276:immunology*; D011134:Polysaccharides / Q000276:immunology*; D011323:Primates / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D011134:Polysaccharides; D014612:Vaccines; D054299:env Gene Products, Human Immunodeficiency Virus; D008358:Mannose
keywords: HIV; V3 glycan; glycan; long-term immunization; vaccination