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 l...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2020
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| Online Access: | https://hdl.handle.net/1721.1/126252 |
| _version_ | 1811073220807229440 |
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| author | 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 |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology 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 |
| author_sort | Tokatlian, Talar |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:30:11Z |
| format | Article |
| id | mit-1721.1/126252 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:30:11Z |
| publishDate | 2020 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1262522022-09-30T14:52:22Z Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers 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 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 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. 2020-07-17T20:29:08Z 2020-07-17T20:29:08Z 2019-02 2018-06 2020-03-09T18:51:15Z Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 https://hdl.handle.net/1721.1/126252 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 en http://dx.doi.org/10.1126/science.aat9120 Science Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | 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 Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers |
| title | Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers |
| title_full | Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers |
| title_fullStr | Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers |
| title_full_unstemmed | Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers |
| title_short | Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers |
| title_sort | innate immune recognition of glycans targets hiv nanoparticle immunogens to germinal centers |
| url | https://hdl.handle.net/1721.1/126252 |
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