Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers
Name
nihms-1012263.pdf
Description
Accepted version
Size
1.62 MB
Format
Adobe PDF
Checksum (MD5)
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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.
Date Issued
February 2019
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
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.
MIT 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
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1126/science.aat9120
