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

TitleEnhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16.
Publication TypeJournal Article
Year of Publication2016
AuthorsGunn BM, Schneider JR, Shansab M, Bastian AR, Fahrbach KM, Smith AD, Mahan AE, Karim MM, Licht AF, Zvonar I, Tedesco J, Anderson MR, Chapel A, Suscovich TJ, Malaspina DC, Streeck H, Walker BD, Kim A, Lauer G, Altfeld M, Pillai S, Szleifer I, Kelleher NL, Kiser PF, Hope TJ, Alter G
JournalMucosal Immunol
Volume9
Issue6
Pagination1549-1558
Date Published2016 Nov
ISSN1935-3456
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.

DOI10.1038/mi.2016.8
Alternate JournalMucosal Immunol
PubMed ID26960182
PubMed Central IDPMC5017893
Grant ListP30 AI117943 / AI / NIAID NIH HHS / United States
R33 AI094584 / AI / NIAID NIH HHS / United States
R37 AI080289 / AI / NIAID NIH HHS / United States
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