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...

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Bibliographic Details
Published in:Biomacromolecules 2019-12, Vol.20 (12), p.4370-4379
Main Authors: Bennett, Nitasha R, Jarvis, Cassie M, Alam, Mohammad Murshid, Zwick, Daniel B, Olson, Jake M, Nguyen, Hung V.-T, Johnson, Jeremiah A, Cook, Mark E, Kiessling, Laura L
Format: Article
Language:English
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Summary: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.
ISSN:1525-7797
1526-4602
DOI:10.1021/acs.biomac.9b01049