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.
journal_name
Biomacromoleculesjournal_title
Biomacromoleculesauthors
Bennett NR,Jarvis CM,Alam MM,Zwick DB,Olson JM,Nguyen HV,Johnson JA,Cook ME,Kiessling LLdoi
10.1021/acs.biomac.9b01049subject
Has Abstractpub_date
2019-12-09 00:00:00pages
4370-4379issue
12eissn
1525-7797issn
1526-4602journal_volume
20pub_type
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