title: β-Glucan microparticles are good candidates for mucosal antigen delivery in oral vaccination.
abstract: Continuously improving the developmental process and the efficacy of oral vaccines is essential in the fight against intestinal pathogens. A promising strategy for vaccination applying safe, biodegradable and non-replicating antigen delivery systems has gained increased interest for eliciting cellular and humoral immune responses. The current study evaluates the potential of β-glucan particles (GP) as an oral antigen delivery system and their adjuvant characteristics. GP are efficiently internalized by human intestinal epithelial cell lines (Caco-2 and HT-29 cells), without exerting negative effects on cell viability. GP triggered the expression of pro-inflammatory cytokines IL-23p19, IL-8 and the β-glucan receptors dectin-1 and TLR2 by activated Caco-2 cells, and CCL20 in HT-29 cells. In contrast, the expression level of TGF-β, an important mediator of oral tolerance, was significantly downregulated in HT-29 cells. Additionally, adoptive transfer experiments showed proliferating ovalbumin (OVA)-specific CD4(+) T cells mainly in the spleens of GP-OVA-fed mice. Furthermore, we detected a significantly increased IL-17 and a trend towards increased IFN-γ production in the spleen of GP-OVA-fed mice upon antigen restimulation. Oral administration of GP-OVA induced increased OVA-specific IgA, secretory-IgA (S-IgA) and secretory component (SC) production in intestinal fluids. Our data show that GP vehicles are able to deliver OVA via an oral route allowing efficient antigen presentation alongside adaptive immune activation, resulting in a Th17-biased response and the production of OVA-specific IgA, secretory-IgA and secretory component antibodies.
authors.affiliation: Department of Pathology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: rebecca.desmet@ugent.be.
authors.forename: Rebecca
authors.initials: R
authors.lastname: De Smet
authors.forename: Tine
authors.initials: T
authors.lastname: Demoor
authors.forename: Stephanie
authors.initials: S
authors.lastname: Verschuere
authors.forename: Melissa
authors.initials: M
authors.lastname: Dullaers
authors.forename: Gary R
authors.initials: GR
authors.lastname: Ostroff
authors.forename: Georges
authors.initials: G
authors.lastname: Leclercq
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Allais
authors.forename: Charles
authors.initials: C
authors.lastname: Pilette
authors.forename: Marijke
authors.initials: M
authors.lastname: Dierendonck
authors.forename: Bruno G
authors.initials: BG
authors.lastname: De Geest
authors.forename: Claude A
authors.initials: CA
authors.lastname: Cuvelier
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018938:Caco-2 Cells; D016207:Cytokines / Q000276:immunology; D019073:HT29 Cells; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D014611:Vaccination; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology; D047071:beta-Glucans / Q000737:chemistry / Q000276:immunology*
chemical_list: D000941:Antigens; D016207:Cytokines; D007070:Immunoglobulin A; D014612:Vaccines; D047071:beta-Glucans; D010047:Ovalbumin
keywords: Antigen delivery; GP; MLN; Oral vaccination; PP; PRR; Peyer's patches; S-IgA; SC; Vaccines; mesenteric lymph nodes; pIgR; pattern recognition receptor; polymeric immunoglobulin receptor; secretory component; secretory-immunoglobulin A; β-glucan microparticles