title: Nanoporous polyelectrolyte vaccine microcarriers. A formulation platform for enhancing humoral and cellular immune responses.
abstract: In this paper we report on the design, characterization and immuno-biological evaluation of nanoporous polyelectrolyte microparticles as vaccine carrier. Relative to soluble antigen, formulation of antigen as a sub-10 μm particle can strongly enhance antigen-specific cellular immune responses. The latter is crucial to confer protective immunity against intracellular pathogens and for anti-cancer vaccines. However, a major bottleneck in microparticulate vaccine formulation is the development of generic strategies that afford antigen encapsulation under benign and scalable conditions. Our strategy is based on spray drying of a dilute aqueous solution of antigen, oppositely charged polyelectrolytes and mannitol as a pore-forming component. The obtained solid microparticles can be redispersed in aqueous medium, leading to leaching out of the mannitol, thereby creating a highly porous internal structure. This porous structure enhances enzymatic processing of encapsulated proteins. After optimizing the conditions to process these microparticles we demonstrate that they strongly enhance cross-presentation in vitro by dendritic cells to CD8 T cells. In vivo experiments in mice confirm that this vaccine formulation technology is capable of enhancing cellular immune responses.
authors: Department of Pharmaceutics, Ghent University, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Zwijnaarde, Ghent, Belgium.
authors: Stefaan
authors: S
authors: De Koker
authors: VIB Inflammation Research Center, University of Ghent, Ghent, Belgium; Department of Respiratory Medicine, University Hospital Ghent, Ghent, Belgium.
authors: Kaat
authors: K
authors: Fierens
authors: Department of Pharmaceutics, Ghent University, Ghent, Belgium.
authors: Marijke
authors: M
authors: Dierendonck
authors: VIB Inflammation Research Center, University of Ghent, Ghent, Belgium; Department of Plant Systems Biology, VIB, and Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium.
authors: Riet
authors: R
authors: De Rycke
authors: VIB Inflammation Research Center, University of Ghent, Ghent, Belgium; Department of Respiratory Medicine, University Hospital Ghent, Ghent, Belgium.
authors: Bart N
authors: BN
authors: Lambrecht
authors: Department of Biomedical Molecular Biology, Ghent University, Zwijnaarde, Ghent, Belgium.
authors: Johan
authors: J
authors: Grooten
authors: Department of Pharmaceutics, Ghent University, Ghent, Belgium.
authors: Jean Paul
authors: JP
authors: Remon
authors: Department of Pharmaceutics, Ghent University, Ghent, Belgium. Electronic address: br.degeest@ugent.be.
authors: Bruno G
authors: BG
authors: De Geest
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016264:Dextran Sulfate / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D008353:Mannitol / Q000737:chemistry*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D016062:Porosity; D014612:Vaccines / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D010455:Peptides; D014612:Vaccines; C015462:polyarginine; D008353:Mannitol; D010047:Ovalbumin; D016264:Dextran Sulfate
keywords: Antigens; Microparticles; Polyelectrolytes; Spray drying; Vaccines