Baert, Kim

Cox, Eric

De Geest, Bruno

Devriendt, Bert

Dierendonck, Marijke

Favoreel, Herman

Remon, Jean Paul

English

Ghent University Academic Bibliography

One step spray-dried polyelectrolyte microparticles enhance the antigen cross-presentation capacity of porcine dendritic cells  Bert DEVRIENDT1,*, Kim BAERT1, Marijke DIERENDONCK2, Herman FAVOREEL1, Jean Paul REMON2, Bruno G. DE GEEST2, Eric COX1   1Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium; 2Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000, Ghent, Belgium  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 the antigens in biodegradable microparticulate delivery systems seems a promising strategy to boost their immunogenicity. Here, we evaluate the capacity of polyelectrolyte microparticles (PEMs), 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). PEMs were loaded with either BSA-FITC or F4 fimbriae, a bacterial adhesin purified from a porcine-specific enterotoxigenic E. coli strain, by co-spray-drying with the PEM constituents, the polyelectrolytes dextran-sulphate and poly-L-arginine and the sacrificial template mannitol. In vitro generated porcine monocyte-derived dendritic cells were incubated with these PEMs and the phenotypical and functional DC maturation was assessed by confocal and live cell imaging, flow cytometry, proliferation assays and cytokine ELISAs. In confocal images we detected multiple particles per cell in >80% of the examined DCs, indicating that the resulting antigen-loaded PEMs were efficiently internalised by porcine monocyte-derived DCs. F4 fimbriae-loaded PEMs (F4-PEMs) 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-PEMs enhance both the T cell stimulatory and antigen presentation capacity of DCs. Moreover, PEMs efficiently promoted the CD8+ T cell stimulatory capacity of dendritic cells, indicating an enhanced ability to cross-present the encapsulated antigens. Our results confirm recent data obtained in rodent models that single step spray-dried PEMs boost the immunogenicity of vaccine antigens and could accelerate the development of veterinary and human subunit vaccines based on polyelectrolyte microparticulate delivery systems to protect against a variety of extra- and intracellular pathogens. 

Single step spray-dried polyelectrolyte microparticles enhance the antigen cross-presentation capacity of porcine dendritic cells

https://biblio.ugent.be/publication/3035088/file/3035113

Single step spray-dried polyelectrolyte microparticles enhance the antigen cross-presentation capacity of porcine dendritic cells

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Ghent University Academic Bibliography