Modular Polymer Antigens To Optimize Immunity.

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

Biomacromolecules

journal_title

Biomacromolecules

authors

Bennett NR,Jarvis CM,Alam MM,Zwick DB,Olson JM,Nguyen HV,Johnson JA,Cook ME,Kiessling LL

doi

10.1021/acs.biomac.9b01049

subject

Has Abstract

pub_date

2019-12-09 00:00:00

pages

4370-4379

issue

12

eissn

1525-7797

issn

1526-4602

journal_volume

20

pub_type

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