β-glucan microparticles targeted to epithelial APN as oral antigen delivery system.
Enteric diseases still have a devastating impact on global health. Oral vaccination is crucial to prevent intestinal infections, since only vaccines delivered to the intestinal tract elicit potent immune responses at the site of pathogen entry. However, oral vaccines encounter multiple barriers, including poor uptake and tolerance mechanisms, preventing the immune system to react to innocuous environmental antigens. Antigen delivery systems combined with selective targeting seem a promising strategy to overcome these obstacles. The current study evaluates the capacity of aminopeptidase N (APN)-targeted β-glucan microparticles (GPs) as antigen delivery system. Antibodies against APN, an intestinal epithelial receptor, are efficiently oriented conjugated to GPs via the biolinker protein G. The resultant microparticles were analyzed for their antigen load, adjuvanticity and interaction with enterocytes and dendritic cells (DCs). Functionalization of GPs with antibodies neither impedes antigen load nor adjuvanticity. In addition, targeting to APN increases the uptake of microparticles by enterocytes and DCs, leading to an enhanced maturation of the latter as evidenced by an upregulation of maturation markers and a strong pro-inflammatory cytokine response. Finally, oral administration of APN-targeted antigen-loaded particles to piglets elicits higher serum antigen-specific antibody responses as compared to control particles. Taken together, these data support the use of APN-targeted GPs for oral delivery of antigens.
Department of Immunology, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. Electronic address: ksbaert.baert@ugent.be.
Kim
K
Baert
Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
Bruno G
BG
de Geest
Department of Biomedical Molecular Biology, Ghent University, Technologiepark Zwijn. 927 VIB west, 9052 Zwijnaarde, Ghent, Belgium.
Riet
R
de Rycke
Department of Molecular Biomedical Research, VIB, Rijvisschestraat 120, 9052 Zwijnaarde, Ghent, Belgium.
André B
AB
da Fonseca Antunes
Structural and Molecular Microbiology, Structural Biology Research Centre, VIB, Pleinlaan 2, 1050 Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
Henri
H
de Greve
Department of Immunology, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
Eric
E
Cox
Department of Immunology, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
Bert
B
Devriendt
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000941:Antigens / Q000008:administration & dosage*; D018826:CD13 Antigens / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D007114:Immunization; D007413:Intestinal Mucosa / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000008:administration & dosage; D013552:Swine; D047071:beta-Glucans / Q000737:chemistry* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000941:Antigens; D047071:beta-Glucans; D012710:Serum Albumin, Bovine; D018826:CD13 Antigens
Antigen delivery; Dendritic cells; Epithelial targeting; Functional antibody conjugation; Protein G; β-glucan microparticles