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

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.
0036-8075
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
4750d8ea-f622-4d75-8423-67e881fa6c15
Chang, Jason Y. H.
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Steichen, Jon M.
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Kumari, Sudha
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Allen, Joel D.
c873d886-2a66-475b-ae04-57a10b37e716
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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Tokatlian, Talar
a8f2bfca-b646-4ae5-848a-6d6024badb88
Read, Benjamin J.
a93c0d94-de24-4b24-92b8-896684e448c0
Jones, Christopher A.
e705c242-4dd2-42b2-a8d3-d25ef5b6c954
Kulp, Daniel W.
3f4e260a-84f2-4140-b557-9bc3cb0947e7
Menis, Sergey
4750d8ea-f622-4d75-8423-67e881fa6c15
Chang, Jason Y. H.
c1ace236-d6cf-4fd5-acc4-dc7603e59e66
Steichen, Jon M.
53e5c7c4-5a1e-4f4e-8d03-1486b670b425
Kumari, Sudha
98dfd877-d221-4eda-b1a2-510612e5953a
Allen, Joel D.
c873d886-2a66-475b-ae04-57a10b37e716
Dane, Eric L.
efc83023-63e9-4204-a3e2-9714064011d1
Liguori, Alessia
a2ba24a9-ef50-43de-b095-a59eee87f260
Sangesland, Maya
55eb6e02-daa3-44d0-91f0-f02a3a1d328c
Lingwood, Daniel
988362d2-3f1e-4144-b47b-aa8c55f03473
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
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), 649-654, [eaat9120]. (doi:10.1126/science.aat9120).

Record type: Article

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
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

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Date deposited: 20 Mar 2019 17:30
Last modified: 15 Sep 2021 02:13

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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: Joel D. Allen
Author: Eric L. Dane
Author: Alessia Liguori
Author: Maya Sangesland
Author: Daniel Lingwood
Author: Max Crispin ORCID iD
Author: William R. Schief
Author: Darrell J. Irvine

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