Assembly of poly(I:C) on microspheres modulates phagocytic dendritic cell rsponsiveness via interaction with TLR3

Project Leader

Blaise CORTHESY, Ph.D., M.E.R.

Short CV

In collaboration with
Annina Hafner and Hans-Peter Merkle, ETH-Zürich

The dsRNA polyriboninosinic acid-polyribocytidylic acid, poly(I:C), is a promising adjuvant candidate for vaccination when cell-mediated immunity is required. In order to avoid side-effects including inflammation and autoimmunity symptoms, poly(I:C) has to be delivered in optimal amounts. In this project, assembly of poly(I:C) on surface-modified polystyrene microspheres results in a 100-fold higher maturation of monocyte-derived dendritic cells (MoDCs) in comparison with free poly(I:C). Moreover, MoDCs display a high capacity to stimulate T cell proliferation, yet their cytokine secretion pattern after exposure to surface-assembled poly(I:C) is different to that of free poly(I:C). This indicates that phagocytosis in the context of microspheres results in modulated reactivity of MoDCs, and that engineering of poly(I:C)-carrying microspheres may be an asset in term of safety when it comes to use this adjuvant. As a follow-up of this work, surface-assembly of poly(I:C) on pegylated microspheres proves to be useful to avoid adverse over-reactivity of fibroblasts, abundant cells found at the site of intra-cutaneous vaccines.

Surface expression of MHC class I and II molecules on fibroblasts after exposure to surface-assembled poly(I:C) on PS microspheres (dark line), surface-assembled poly(I:C) on PEG-coated PS microspheres (grey line), and PEG-coated PS microspheres (dashed line). Specific reduction of MHC class I takes place with pegylation, while no up-regulation of MHC class II molecules is observed.

Publications
  • Hafner A.M., Corthésy B., Textor M. and Merkle H.P. Tuning the immune response of dendritic cells to surface-assembled poly(I:C) on microspheres through synergistic interactions between phagocytotic and TLR3 signaling. Biomaterials 2011, 32:2651-2661. PubMed
  • Hafner A.M., Burschwosky D., Corthésy B., Textor M. and Merkle H.P. Surface assembly of poly(I:C) on PEGylated microspheres to shield from adverse interactions with fibroblasts. J. Control Release 2012, 159:204-214. PubMed
 Dernière mise à jour le 26/06/2018 à 09:23