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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Main Authors:	Gunn, Bronwyn, Schneider, Jeffrey, Shansab, Maryam, Bastian, Arangassery Rosemary, Fahrbach, Kelly, Smith, Archer, Mahan, Alison, Karim, Marcus, Licht, Anna, Zvonar, Ivan, Tedesco, Jacquelynn, Anderson, Meegan, Chapel, Anais, Suscovich, Todd, Malaspina, David, Streeck, Hendrik, Walker, Bruce D., Kim, Arthur, Lauer, Georg, Altfeld, Marcus, Pillai, Shiv, Szleifer, Igal, Kelleher, Neil L., Kiser, Patrick F., Hope, Thomas J., Alter, Galit
Format:	Online
Language:	English
Published:	2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017893/

id	pubmed-5017893
recordtype	oai_dc
spelling	pubmed-50178932016-10-14 Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16 Gunn, Bronwyn Schneider, Jeffrey Shansab, Maryam Bastian, Arangassery Rosemary Fahrbach, Kelly Smith, Archer Mahan, Alison Karim, Marcus Licht, Anna Zvonar, Ivan Tedesco, Jacquelynn Anderson, Meegan Chapel, Anais Suscovich, Todd Malaspina, David Streeck, Hendrik Walker, Bruce D. Kim, Arthur Lauer, Georg Altfeld, Marcus Pillai, Shiv Szleifer, Igal Kelleher, Neil L. Kiser, Patrick F. Hope, Thomas J. Alter, Galit Article 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, 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. 2016-03-09 2016-11 /pmc/articles/PMC5017893/ /pubmed/26960182 http://dx.doi.org/10.1038/mi.2016.8 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Gunn, Bronwyn Schneider, Jeffrey Shansab, Maryam Bastian, Arangassery Rosemary Fahrbach, Kelly Smith, Archer Mahan, Alison Karim, Marcus Licht, Anna Zvonar, Ivan Tedesco, Jacquelynn Anderson, Meegan Chapel, Anais Suscovich, Todd Malaspina, David Streeck, Hendrik Walker, Bruce D. Kim, Arthur Lauer, Georg Altfeld, Marcus Pillai, Shiv Szleifer, Igal Kelleher, Neil L. Kiser, Patrick F. Hope, Thomas J. Alter, Galit
spellingShingle	Gunn, Bronwyn Schneider, Jeffrey Shansab, Maryam Bastian, Arangassery Rosemary Fahrbach, Kelly Smith, Archer Mahan, Alison Karim, Marcus Licht, Anna Zvonar, Ivan Tedesco, Jacquelynn Anderson, Meegan Chapel, Anais Suscovich, Todd Malaspina, David Streeck, Hendrik Walker, Bruce D. Kim, Arthur Lauer, Georg Altfeld, Marcus Pillai, Shiv Szleifer, Igal Kelleher, Neil L. Kiser, Patrick F. Hope, Thomas J. Alter, Galit Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16
author_facet	Gunn, Bronwyn Schneider, Jeffrey Shansab, Maryam Bastian, Arangassery Rosemary Fahrbach, Kelly Smith, Archer Mahan, Alison Karim, Marcus Licht, Anna Zvonar, Ivan Tedesco, Jacquelynn Anderson, Meegan Chapel, Anais Suscovich, Todd Malaspina, David Streeck, Hendrik Walker, Bruce D. Kim, Arthur Lauer, Georg Altfeld, Marcus Pillai, Shiv Szleifer, Igal Kelleher, Neil L. Kiser, Patrick F. Hope, Thomas J. Alter, Galit
author_sort	Gunn, Bronwyn
title	Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16
title_short	Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16
title_full	Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16
title_fullStr	Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16
title_full_unstemmed	Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16
title_sort	enhanced binding of antibodies generated during chronic hiv infection to mucus component muc16
description	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, 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.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017893/
_version_	1613648003759865856

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

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