Modular polymer antigens to optimize immunity
Name
Manuscript.polymer_invivo_LLK_JJ_CMJ_10_05_19.pdf
Description
Accepted version
Size
1.14 MB
Format
Adobe PDF
Checksum (MD5)
483a926a533dd15c99fa53d48113ca0f
Name
BennetSupportingInfo_LLK_10_01_19.pdf
Description
Accepted version
Size
8.04 MB
Format
Adobe PDF
Checksum (MD5)
6a90d3553ecd335a16bc86be2d295c93
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
Date Issued
October 2019
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
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
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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DOI of Published Version
https://doi.org/10.1021/ACS.BIOMAC.9B01049
