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A generic polymer-protein ligation strategy for vaccine delivery

Lien Lybaert (UGent) , Nane Vanparijs (UGent) , Kaat Fierens (UGent) , Martijn Schuijs (UGent) , Lutz Nuhn (UGent) , Bart Lambrecht (UGent) and Bruno De Geest (UGent)
(2016) BIOMACROMOLECULES. 17(3). p.874-881
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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.
Keywords
DENDRITIC CELLS, CANCER-IMMUNOTHERAPY, RAFT POLYMERIZATION, CROSS-PRESENTATION, EXOGENOUS ANTIGENS, CARRIERS, IMMUNITY, IMMUNOGENICITY, NANOPARTICLES, NANOSCALE

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Chicago
Lybaert, Lien, Nane Vanparijs, Kaat Fierens, Martijn Schuijs, Lutz Nuhn, Bart Lambrecht, and Bruno De Geest. 2016. “A Generic Polymer-protein Ligation Strategy for Vaccine Delivery.” Biomacromolecules 17 (3): 874–881.
APA
Lybaert, L., Vanparijs, N., Fierens, K., Schuijs, M., Nuhn, L., Lambrecht, B., & De Geest, B. (2016). A generic polymer-protein ligation strategy for vaccine delivery. BIOMACROMOLECULES, 17(3), 874–881.
Vancouver
1.
Lybaert L, Vanparijs N, Fierens K, Schuijs M, Nuhn L, Lambrecht B, et al. A generic polymer-protein ligation strategy for vaccine delivery. BIOMACROMOLECULES. 2016;17(3):874–81.
MLA
Lybaert, Lien, Nane Vanparijs, Kaat Fierens, et al. “A Generic Polymer-protein Ligation Strategy for Vaccine Delivery.” BIOMACROMOLECULES 17.3 (2016): 874–881. Print.
@article{8501800,
  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.},
  author       = {Lybaert, Lien and Vanparijs, Nane and Fierens, Kaat and Schuijs, Martijn and Nuhn, Lutz and Lambrecht, Bart and De Geest, Bruno},
  issn         = {1525-7797},
  journal      = {BIOMACROMOLECULES},
  keyword      = {DENDRITIC CELLS,CANCER-IMMUNOTHERAPY,RAFT POLYMERIZATION,CROSS-PRESENTATION,EXOGENOUS ANTIGENS,CARRIERS,IMMUNITY,IMMUNOGENICITY,NANOPARTICLES,NANOSCALE},
  language     = {eng},
  number       = {3},
  pages        = {874--881},
  title        = {A generic polymer-protein ligation strategy for vaccine delivery},
  url          = {http://dx.doi.org/10.1021/acs.biomac.5b01571},
  volume       = {17},
  year         = {2016},
}

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