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Modular polymer antigens to optimize immunity

Author(s)
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; ... Show more Show less
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Publisher Policy

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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.

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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.
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Abstract
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.
Date issued
2019-10
URI
https://hdl.handle.net/1721.1/129449
Department
Massachusetts Institute of Technology. Department of Chemistry; Koch Institute for Integrative Cancer Research at MIT
Journal
Biomacromolecules
Publisher
American Chemical Society (ACS)
Citation
Bennett, Nitasha R. et al. "Modular polymer antigens to optimize immunity." Biomacromolecules 20, 12 (October 2019): 4370-79 ©2019 American Chemical Society
Version: Author's final manuscript
ISSN
1525-7797
1526-4602

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