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Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers

Author(s)
Tokatlian, Talar; Read, Benjamin J.; Jones, Christopher A.; Kulp, Daniel W.; Menis, Sergey; Chang, Jason Y. H.; Steichen, Jon M.; Kumari, Sudha; Allen, Joel D.; Dane, Eric L.; Liguori, Alessia; Sangesland, Maya; Lingwood, Daniel; Crispin, Max; Schief, William R.; Irvine, Darrell J; ... Show more Show less
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Abstract
In vaccine design, antigens are often arrayed in a multivalent nanoparticle form, but in vivo mechanisms underlying the enhanced immunity elicited by such vaccines remain poorly understood. We compared the fates of two different heavily glycosylated HIV antigens, a gp120-derived mini-protein and a large, stabilized envelope trimer, in protein nanoparticle or “free” forms after primary immunization. Unlike monomeric antigens, nanoparticles were rapidly shuttled to the follicular dendritic cell (FDC) network and then concentrated in germinal centers in a complement-, mannose-binding lectin (MBL)–, and immunogen glycan–dependent manner. Loss of FDC localization in MBL-deficient mice or via immunogen deglycosylation significantly affected antibody responses. These findings identify an innate immune–mediated recognition pathway promoting antibody responses to particulate antigens, with broad implications for humoral immunity and vaccine design.
Date issued
2019-02
URI
https://hdl.handle.net/1721.1/126252
Department
Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Materials Science and Engineering; Koch Institute for Integrative Cancer Research at MIT
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Tokatlian, Talar et al. "Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers." Science 363, 6427 (February 2019): 649-654 © 2017 The Authors
Version: Author's final manuscript
ISSN
0036-8075
1095-9203

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