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Potent anti-viral vaccine adjuvant based on pH-degradable nanogels with covalently linked small molecule imidazoquinoline TLR7/8 agonist.
Nuhn, Lutz; Van Hoecke, Lien; Deswarte, Kim; Schepens, Bert; Li, Yupeng; Lambrecht, Bart N; De Koker, Stefaan; David, Sunil A; Saelens, Xavier; De Geest, Bruno G.
Afiliação
  • Nuhn L; Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
  • Van Hoecke L; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark 927, 9052 Zwijnaarde, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052 Ghent, Belgium.
  • Deswarte K; VIB-UGent Center for Inflammation Research, VIB, Technologiepark 927, 9052 Zwijnaarde, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium.
  • Schepens B; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark 927, 9052 Zwijnaarde, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052 Ghent, Belgium.
  • Li Y; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
  • Lambrecht BN; VIB-UGent Center for Inflammation Research, VIB, Technologiepark 927, 9052 Zwijnaarde, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium.
  • De Koker S; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark 927, 9052 Zwijnaarde, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052 Ghent, Belgium.
  • David SA; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
  • Saelens X; VIB-UGent Center for Medical Biotechnology, VIB, Technologiepark 927, 9052 Zwijnaarde, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052 Ghent, Belgium.
  • De Geest BG; Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: br.degeest@ugent.be.
Biomaterials ; 178: 643-651, 2018 09.
Article em En | MEDLINE | ID: mdl-29573820
ABSTRACT
Improving the immunogenicity of subunit vaccines, in particular skewing of the immune response towards Th1 type immunity, is crucial for the development of effective vaccines against intracellular infections and for the development of anti-cancer vaccines. Small molecule TLR7/8 agonist hold high potential for this purpose, but suffer from an undesirable pharmacokinetic profile, resulting in systemic inflammatory responses. An effective solution to this problem is covalent ligation to a larger carrier. Here, a degradable nanogel carrier containing a covalently linked imidazoquinoline (IMDQ) TLR7/8 agonist is explored as adjuvant for vaccination against the respiratory syncytial virus (RSV). In vitro and in vivo experiments in mice provide a solid rational base for preferring nanogels over soluble polymers as IMDQ carrier in terms of cellular uptake and lymph node accumulation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antivirais / Polietilenoglicóis / Polietilenoimina / Quinolinas / Vacinas Virais / Adjuvantes Imunológicos / Receptor 7 Toll-Like / Receptor 8 Toll-Like / Imidazóis Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antivirais / Polietilenoglicóis / Polietilenoimina / Quinolinas / Vacinas Virais / Adjuvantes Imunológicos / Receptor 7 Toll-Like / Receptor 8 Toll-Like / Imidazóis Idioma: En Ano de publicação: 2018 Tipo de documento: Article