Targeting polymerised liposome vaccine carriers to intestinal M cells.
Due to their transcytotic capability, intestinal M cells may represent an efficient potential route for oral vaccine delivery. We previously demonstrated that the lectin Ulex europaeus agglutinin 1 (UEA1, specific for alpha-L-fucose residues) selectively binds to mouse Peyer's patch M cells and targets 0.5 microm polystyrene microparticles to these cells. Using a gut loop model we now demonstrate that covalently-membrane-bound UEA1 similarly targets polymerised liposomes (Orasomes, approximately 200 nm diameter), potential biocompatable oral vaccine delivery vehicles, to mouse M cells. Targeting was inhibited by alpha-L-fucose while the co-entrapped adjuvant, monophosphoryl Lipid A (MPL), failed to exert any detrimental effect on UEA1-mediated M cell targeting. Lectin-mediated M cell targeting may thus permit the efficacy of mucosal vaccines to be enhanced if cellular relationship between particle binding and immune outcome can be established.
Clark
M A
MA
Department of Physiological Sciences, Medical School, University of Newcastle, NE2 4HH, Newcastle upon Tyne, UK.
Blair
H
H
Liang
L
L
Brey
R N
RN
Brayden
D
D
Hirst
B H
BH
D000818:Animals; D002448:Cell Adhesion; D004337:Drug Carriers / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005643:Fucose / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D037102:Lectins / Q000493:pharmacokinetics*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008863:Microspheres; D008871:Microvilli / Q000378:metabolism / Q000648:ultrastructure; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology*; D037121:Plant Lectins; D011108:Polymers; D011137:Polystyrenes; D014612:Vaccines / Q000008:administration & dosage* / Q000493:pharmacokinetics
D004337:Drug Carriers; D037102:Lectins; D008050:Lipid A; D008081:Liposomes; D037121:Plant Lectins; D011108:Polymers; D011137:Polystyrenes; C036850:Ulex europaeus lectins; D014612:Vaccines; D005643:Fucose; C048436:monophosphoryl lipid A