Modular Polymer Antigens To Optimize Immunity

Biomacromolecules. 2019 Dec 9;20(12):4370-4379. doi: 10.1021/acs.biomac.9b01049. Epub 2019 Nov 11.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens* / chemistry
  • Antigens* / pharmacology
  • Epitopes, B-Lymphocyte* / chemistry
  • Epitopes, B-Lymphocyte* / pharmacology
  • Epitopes, T-Lymphocyte* / chemistry
  • Epitopes, T-Lymphocyte* / pharmacology
  • Female
  • Immunoglobulin G / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Polymerization*
  • Vaccines, Subunit / chemical synthesis
  • Vaccines, Subunit / chemistry
  • Vaccines, Subunit / pharmacology


  • Antigens
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Immunoglobulin G
  • Vaccines, Subunit