Modular polymer antigens to optimize immunity
Subunit vaccines can have excellent safety profiles, but their ability to give rise to robust immune responses is often compromised. For glycan-based vaccines, insufficient understanding of B and T cell epitope combinations that yield optimal immune activation hinders optimization. To determine whic...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Chemical Society (ACS)
2021
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| Online Access: | https://hdl.handle.net/1721.1/129449 |
| _version_ | 1826208026518880256 |
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| author | Bennett, Nitasha R Jarvis, Cassie Marie. Alam, Mohammad Murshid Zwick, Daniel B Olson, Jake M Nguyen, Hung V.-T. Johnson, Jeremiah A. Cook, Mark E Kiessling, Laura L |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Bennett, Nitasha R Jarvis, Cassie Marie. Alam, Mohammad Murshid Zwick, Daniel B Olson, Jake M Nguyen, Hung V.-T. Johnson, Jeremiah A. Cook, Mark E Kiessling, Laura L |
| author_sort | Bennett, Nitasha R |
| collection | MIT |
| description | Subunit vaccines can have excellent safety profiles, but their ability to give rise to robust immune responses is often compromised. For glycan-based vaccines, insufficient understanding of B and T cell epitope combinations that yield optimal immune activation hinders optimization. To determine which antigen features promote desired IgG responses, we synthesized epitope-functionalized polymers using ring-opening metathesis polymerization (ROMP) and assessed the effect of B and T cell epitope loading. The most robust responses were induced by polymers with a high valency of B and T cell epitopes. Additionally, IgG responses were greater for polymers with T cell epitopes that are readily liberated upon endosomal processing. Combining these criteria, we used ROMP to generate a nontoxic, polymeric antigen that elicited stronger antibody responses than a comparable protein conjugate. These findings highlight principles for designing synthetic antigens that elicit strong IgG responses against inherently weak immune targets such as glycans. |
| first_indexed | 2024-09-23T13:59:12Z |
| format | Article |
| id | mit-1721.1/129449 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:59:12Z |
| publishDate | 2021 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1294492022-10-01T18:23:01Z Modular polymer antigens to optimize immunity Bennett, Nitasha R Jarvis, Cassie Marie. Alam, Mohammad Murshid Zwick, Daniel B Olson, Jake M Nguyen, Hung V.-T. Johnson, Jeremiah A. Cook, Mark E Kiessling, Laura L Massachusetts Institute of Technology. Department of Chemistry Koch Institute for Integrative Cancer Research at MIT Subunit vaccines can have excellent safety profiles, but their ability to give rise to robust immune responses is often compromised. For glycan-based vaccines, insufficient understanding of B and T cell epitope combinations that yield optimal immune activation hinders optimization. To determine which antigen features promote desired IgG responses, we synthesized epitope-functionalized polymers using ring-opening metathesis polymerization (ROMP) and assessed the effect of B and T cell epitope loading. The most robust responses were induced by polymers with a high valency of B and T cell epitopes. Additionally, IgG responses were greater for polymers with T cell epitopes that are readily liberated upon endosomal processing. Combining these criteria, we used ROMP to generate a nontoxic, polymeric antigen that elicited stronger antibody responses than a comparable protein conjugate. These findings highlight principles for designing synthetic antigens that elicit strong IgG responses against inherently weak immune targets such as glycans. National Institutes of Health (AI055258) 2021-01-19T20:19:32Z 2021-01-19T20:19:32Z 2019-10 2020-10-14T16:28:39Z Article http://purl.org/eprint/type/JournalArticle 1525-7797 1526-4602 https://hdl.handle.net/1721.1/129449 Bennett, Nitasha R. et al. "Modular polymer antigens to optimize immunity." Biomacromolecules 20, 12 (October 2019): 4370-79 ©2019 American Chemical Society en 10.1021/ACS.BIOMAC.9B01049 Biomacromolecules Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf application/pdf American Chemical Society (ACS) Prof. Kiessling via Ye Li |
| spellingShingle | Bennett, Nitasha R Jarvis, Cassie Marie. Alam, Mohammad Murshid Zwick, Daniel B Olson, Jake M Nguyen, Hung V.-T. Johnson, Jeremiah A. Cook, Mark E Kiessling, Laura L Modular polymer antigens to optimize immunity |
| title | Modular polymer antigens to optimize immunity |
| title_full | Modular polymer antigens to optimize immunity |
| title_fullStr | Modular polymer antigens to optimize immunity |
| title_full_unstemmed | Modular polymer antigens to optimize immunity |
| title_short | Modular polymer antigens to optimize immunity |
| title_sort | modular polymer antigens to optimize immunity |
| url | https://hdl.handle.net/1721.1/129449 |
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