A Generic Polymer-Protein Ligation Strategy for Vaccine Delivery.

Abstract:

:Although the field of cancer immunotherapy is intensively investigated, there is still a need for generic strategies that allow easy, mild and efficient formulation of vaccine antigens. Here we report on a generic polymer-protein ligation strategy to formulate protein antigens into reversible polymeric conjugates for enhanced uptake by dendritic cells and presentation to CD8 T-cells. A N-hydroxypropylmethacrylamide (HPMA)-based copolymer was synthesized via RAFT polymerization followed by introduction of pyridyldisulfide moieties. To enhance ligation efficiency to ovalbumin, which is used as a model protein antigen, protected thiols were introduced onto lysine residues and deprotected in situ in the presence of the polymer. The ligation efficiency was compared for both the thiol-modified versus unmodified ovalbumin, and the reversibility was confirmed. Furthermore, the obtained nanoconjugates were tested in vitro for their interaction and association with dendritic cells, showing enhanced cellular uptake and antigen cross-presentation to CD8 T-cells.

journal_name

Biomacromolecules

journal_title

Biomacromolecules

authors

Lybaert L,Vanparijs N,Fierens K,Schuijs M,Nuhn L,Lambrecht BN,De Geest BG

doi

10.1021/acs.biomac.5b01571

subject

Has Abstract

pub_date

2016-03-14 00:00:00

pages

874-81

issue

3

eissn

1525-7797

issn

1526-4602

journal_volume

17

pub_type

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