Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers
Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers
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.
649-654
Tokatlian, Talar
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Read, Benjamin J.
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Jones, Christopher A.
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Kulp, Daniel W.
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Menis, Sergey
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Chang, Jason Y. H.
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Steichen, Jon M.
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Kumari, Sudha
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Allen, Joel D.
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Dane, Eric L.
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Liguori, Alessia
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Sangesland, Maya
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Lingwood, Daniel
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Crispin, Max
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Schief, William R.
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Irvine, Darrell J.
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8 February 2019
Tokatlian, Talar
a8f2bfca-b646-4ae5-848a-6d6024badb88
Read, Benjamin J.
a93c0d94-de24-4b24-92b8-896684e448c0
Jones, Christopher A.
112ffd4f-3f23-4e64-ac88-e8bb9408154f
Kulp, Daniel W.
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Menis, Sergey
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Chang, Jason Y. H.
c1ace236-d6cf-4fd5-acc4-dc7603e59e66
Steichen, Jon M.
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Kumari, Sudha
98dfd877-d221-4eda-b1a2-510612e5953a
Allen, Joel D.
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Dane, Eric L.
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Liguori, Alessia
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Sangesland, Maya
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Lingwood, Daniel
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Crispin, Max
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Schief, William R.
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Irvine, Darrell J.
63f295b5-7d49-4c85-9e9b-4797cebf5f89
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. and Irvine, Darrell J.
(2019)
Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers.
Science, 363 (6427), , [eaat9120].
(doi:10.1126/science.aat9120).
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.
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Accepted/In Press date: 12 December 2018
e-pub ahead of print date: 8 February 2019
Published date: 8 February 2019
Identifiers
Local EPrints ID: 429093
URI: http://eprints.soton.ac.uk/id/eprint/429093
ISSN: 0036-8075
PURE UUID: fc350291-344e-4bc5-9116-35feada5a74e
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Date deposited: 20 Mar 2019 17:30
Last modified: 16 Mar 2024 04:46
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Contributors
Author:
Talar Tokatlian
Author:
Benjamin J. Read
Author:
Christopher A. Jones
Author:
Daniel W. Kulp
Author:
Sergey Menis
Author:
Jason Y. H. Chang
Author:
Jon M. Steichen
Author:
Sudha Kumari
Author:
Eric L. Dane
Author:
Alessia Liguori
Author:
Maya Sangesland
Author:
Daniel Lingwood
Author:
William R. Schief
Author:
Darrell J. Irvine
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