title: One-step spray-dried polyelectrolyte microparticles enhance the antigen cross-presentation capacity of porcine dendritic cells.
abstract: Vaccination is regarded as the most efficient and cost-effective way to prevent infectious diseases. Vaccine design nowadays focuses on the implementation of safer recombinant subunit vaccines. However, these recombinant subunit antigens are often poor immunogens and several strategies are currently under investigation to enhance their immunogenicity. The encapsulation of antigens in biodegradable microparticulate delivery systems seems a promising strategy to boost their immunogenicity. Here, we evaluate the capacity of polyelectrolyte complex microparticles (PECMs), fabricated by single step spray-drying, to deliver antigens to porcine dendritic cells and how these particles affect the functional maturation of dendritic cells (DCs). As clinically relevant model antigen F4 fimbriae, a bacterial adhesin purified from a porcine-specific enterotoxigenic Escherichia coli strain was chosen. The resulting antigen-loaded PECMs are efficiently internalised by porcine monocyte-derived DCs. F4 fimbriae-loaded PECMs (F4-PECMs) enhanced CD40 and CD25 surface expression by DCs and this phenotypical maturation correlated with an increased secretion of IL-6 and IL-1β. More importantly, F4-PECMs enhance both the T cell stimulatory and antigen presentation capacity of DCs. Moreover, PECMs efficiently promoted the CD8(+) T cell stimulatory capacity of dendritic cells, indicating an enhanced ability to cross-present the encapsulated antigens. These results could accelerate the development of veterinary and human subunit vaccines based on polyelectrolyte complex microparticles to induce protective immunity against a variety of extra- and intracellular pathogens.
authors.affiliation: Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. b.devriendt@Ugent.be
authors.forename: Bert
authors.initials: B
authors.lastname: Devriendt
authors.forename: Kim
authors.initials: K
authors.lastname: Baert
authors.forename: Marijke
authors.initials: M
authors.lastname: Dierendonck
authors.forename: Herman
authors.initials: H
authors.lastname: Favoreel
authors.forename: Stefaan
authors.initials: S
authors.lastname: De Koker
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.forename: Bruno G
authors.initials: BG
authors.lastname: De Geest
authors.forename: Eric
authors.initials: E
authors.lastname: Cox
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D000942:Antigens, Bacterial / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D045142:Cross-Priming / Q000187:drug effects* / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology*; D004573:Electrolytes / Q000737:chemistry*; D004705:Endocytosis; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D036781:Fimbriae Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D010316:Particle Size; D010641:Phenotype; D013552:Swine
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D019013:CD40 Antigens; D004573:Electrolytes; D029968:Escherichia coli Proteins; D053583:Interleukin-1beta; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; C026888:K88 antigen, E coli; D036781:Fimbriae Proteins