Dynamic Covalent Dextran Hydrogels as Injectable, Self-Adjuvating Peptide Vaccine Depots

ACS Chemical Biology, vol. 18, pp. 652–659

Abstract

Dextran-based hydrogels are promising therapeutic materials for drug delivery, tissue regeneration devices, and cell therapy vectors, due to their high biocompatibility, along with their ability to protect and release active therapeutic agents. This report describes the synthesis, characterization, and application of a new dynamic covalent dextran hydrogel as an injectable depot for peptide vaccines. Dynamic covalent crosslinks based on double Michael addition of thiols to alkynones impart the dextran hydrogel with shear-thinning and self-healing capabilities, enabling hydrogel injection. These injectable, non-toxic hydrogels show adjuvant potential and have predictable sub-millimolar loading and release of the peptide antigen SIINFEKL, which after its release is able to activate T-cells, demonstrating that the hydrogels deliver peptides without modifying their immunogenicity. This work demonstrates the potential of dynamic covalent dextran hydrogels as a sustained-release material for the delivery of peptide vaccines.

Authors 6

1. Bowen Fan

   University of Notre Dame · Delft University of Technology

   Affiliation as printed

   Department of Chemical Engineering, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands

   Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States

2. Diana Torres‐García Aachen Division of Bio-Organic Synthesis Leiden Institute of Chemistry Institute of Chemical Immunology Gorlaeus Laboratory

   Leiden University

   Affiliation as printed

   Division of Bio-Organic Synthesis, Leiden Institute of Chemistry and Institute of Chemical Immunology, Leiden University, Gorlaeus Laboratory, Einsteinweg 55, 2333 CC Leiden, The Netherlands

3. Marziye Salehi Aachen Division of Bio-Organic Synthesis Leiden Institute of Chemistry Institute of Chemical Immunology Gorlaeus Laboratory

   Leiden University · Delft University of Technology

   Affiliation as printed

   Department of Chemical Engineering, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands

   Division of Bio-Organic Synthesis, Leiden Institute of Chemistry and Institute of Chemical Immunology, Leiden University, Gorlaeus Laboratory, Einsteinweg 55, 2333 CC Leiden, The Netherlands

4. Matthew J. Webber

   University of Notre Dame

   Affiliation as printed

   Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States

5. Sander I. van Kasteren corresponding Aachen Division of Bio-Organic Synthesis Leiden Institute of Chemistry Institute of Chemical Immunology Gorlaeus Laboratory

   Leiden University

   Affiliation as printed

   Division of Bio-Organic Synthesis, Leiden Institute of Chemistry and Institute of Chemical Immunology, Leiden University, Gorlaeus Laboratory, Einsteinweg 55, 2333 CC Leiden, The Netherlands

6. Rienk Eelkema corresponding

   Delft University of Technology

   Affiliation as printed

   Department of Chemical Engineering, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands