Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16

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, inc...

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Bibliographic Details
Published in:	Mucosal immunology Vol. 9; no. 6; pp. 1549 - 1558
Main Authors:	Gunn, B M, Schneider, J R, Shansab, M, Bastian, A R, Fahrbach, K M, Smith, A D, Mahan, A E, Karim, M M, Licht, A F, Zvonar, I, Tedesco, J, Anderson, M R, Chapel, A, Suscovich, T J, Malaspina, D C, Streeck, H, Walker, B D, Kim, A, Lauer, G, Altfeld, M, Pillai, S, Szleifer, I, Kelleher, N L, Kiser, P F, Hope, T J, Alter, G
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-11-2016 Elsevier Limited
Subjects:	631/250/2152/2153/1291 631/250/255/1901 631/250/347 631/45/612/1237 Allergology Antibodies Antibody Affinity - immunology Biomedical and Life Sciences Biomedicine CA-125 Antigen - immunology CA-125 Antigen - metabolism Female Gastroenterology Glycosylation HIV Antibodies - immunology HIV Antibodies - metabolism HIV Infections - immunology HIV Infections - metabolism HIV Infections - virology HIV-1 - immunology Humans Immunoglobulin Fc Fragments - immunology Immunoglobulin Fc Fragments - metabolism Immunoglobulin G - immunology Immunology Membrane Proteins - immunology Membrane Proteins - metabolism Mucous Membrane - immunology Mucous Membrane - metabolism Mucous Membrane - virology Mucus - metabolism Protein Binding Vagina
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1933-0219 1935-3456
DOI:	10.1038/mi.2016.8