title: Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16.
abstract: Transmission of HIV across mucosal barriers accounts for the majority of HIV infections worldwide. Thus, efforts aimed at enhancing protective immunity at these sites are a top priority, including increasing virus-specific antibodies (Abs) and antiviral activity at mucosal sites. Mucin proteins, including the largest cell-associated mucin, mucin 16 (MUC16), help form mucus to provide a physical barrier to incoming pathogens. Here, we describe a natural interaction between Abs and MUC16 that is enhanced in specific disease settings such as chronic HIV infection. Binding to MUC16 was independent of IgG subclass, but strongly associated with shorter Ab glycan profiles, with agalactosylated (G0) Abs demonstrating the highest binding to MUC16. Binding of Abs to epithelial cells was diminished following MUC16 knockdown, and the MUC16 N-linked glycans were critical for binding. Further, agalactosylated VRC01 captured HIV more efficiently in MUC16. These data point to a novel opportunity to enrich Abs at mucosal sites by targeting Abs to MUC16 through changes in Fc glycosylation, potentially blocking viral movement and sequestering the virus far from the epithelial border. Thus, next-generation vaccines or monoclonal therapeutics may enhance protective immunity by tuning Ab glycosylation to promote the enrichment of Abs at mucosal barriers.
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard. 400 Technology Square, Cambridge, MA 02139 USA.
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Gunn
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University 303 E Superior St, Chicago, IL 60611 USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schneider
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard. 400 Technology Square, Cambridge, MA 02139 USA.|University of California San Francisco, San Francisco, CA, 94158.
authors.forename: Maryam
authors.initials: M
authors.lastname: Shansab
authors.affiliation: Department of Biomedical Engineering, Department of Chemistry and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208 USA.
authors.forename: Arangassery Rosemary
authors.initials: AR
authors.lastname: Bastian
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University 303 E Superior St, Chicago, IL 60611 USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Fahrbach
authors.affiliation: Department of Chemistry, Molecular Biosciences, and the Proteomics Center of Excellence, Northwestern University, 2145 N. Sheridan Road, Evanston, Illinois 60208, USA.
authors.forename: Archer
authors.initials: A
authors.lastname: Smith
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard. 400 Technology Square, Cambridge, MA 02139 USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Mahan
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard. 400 Technology Square, Cambridge, MA 02139 USA.
authors.forename: Marcus
authors.initials: M
authors.lastname: Karim
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard. 400 Technology Square, Cambridge, MA 02139 USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Licht
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard. 400 Technology Square, Cambridge, MA 02139 USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Zvonar
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard. 400 Technology Square, Cambridge, MA 02139 USA.
authors.forename: Jacquelynn
authors.initials: J
authors.lastname: Tedesco
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University 303 E Superior St, Chicago, IL 60611 USA.
authors.forename: Meegan
authors.initials: M
authors.lastname: Anderson
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard. 400 Technology Square, Cambridge, MA 02139 USA.|Heinrich Pette Institute, Hamburg, Germany.
authors.forename: Anais
authors.initials: A
authors.lastname: Chapel
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard. 400 Technology Square, Cambridge, MA 02139 USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Suscovich
authors.affiliation: Department of Biomedical Engineering, Department of Chemistry and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208 USA.
authors.forename: David
authors.initials: D
authors.lastname: Malaspina
authors.affiliation: Military HIV Research Program, Bethesda, MD, 20817.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard. 400 Technology Square, Cambridge, MA 02139 USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: Masschusetts General Hospital, 149 13 Street, Charlestown, MA, 02129.
authors.forename: Arthur
authors.initials: A
authors.lastname: Kim
authors.affiliation: Masschusetts General Hospital, 149 13 Street, Charlestown, MA, 02129.
authors.forename: Georg
authors.initials: G
authors.lastname: Lauer
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard. 400 Technology Square, Cambridge, MA 02139 USA.|Heinrich Pette Institute, Hamburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard. 400 Technology Square, Cambridge, MA 02139 USA.|Masschusetts General Hospital, 149 13 Street, Charlestown, MA, 02129.
authors.forename: Shiv
authors.initials: S
authors.lastname: Pillai
authors.affiliation: Department of Biomedical Engineering, Department of Chemistry and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208 USA.
authors.forename: Igal
authors.initials: I
authors.lastname: Szleifer
authors.affiliation: Department of Chemistry, Molecular Biosciences, and the Proteomics Center of Excellence, Northwestern University, 2145 N. Sheridan Road, Evanston, Illinois 60208, USA.
authors.forename: Neil L
authors.initials: NL
authors.lastname: Kelleher
authors.affiliation: Department of Biomedical Engineering, Department of Chemistry and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208 USA.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Kiser
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University 303 E Superior St, Chicago, IL 60611 USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hope
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard. 400 Technology Square, Cambridge, MA 02139 USA.
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
mesh_terms: D000915:Antibody Affinity / Q000276:immunology; D018394:CA-125 Antigen / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006031:Glycosylation; D015483:HIV Antibodies / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009093:Mucus / Q000378:metabolism; D011485:Protein Binding; D014621:Vagina
chemical_list: D018394:CA-125 Antigen; D015483:HIV Antibodies; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; C451759:MUC16 protein, human; D008565:Membrane Proteins