Immunoreactivity in mammals of two typical plant glyco-epitopes, core alpha(1,3)-fucose and core xylose.
The presence of nonmammalian core alpha(1,3)-fucose and core xylose glyco-epitopes on glycans N-linked to therapeutic glycoproteins produced in plants has raised the question of their immunogenicity in human therapy. We address this question by studying the distribution of these N-glycans in pea, rice, and maize (which are the crops intended for the production of therapeutic proteins) and by reinvestigating their immunogenicity in rodents. We found that immunization with a model glycoprotein, horseradish peroxidase, elicits in C57BL/6 mice and rats the production of antibodies (Abs) specific for core alpha(1,3)-fucose and core xylose epitopes. Furthermore, we demonstrated that about 50% of nonallergic blood donors contains in their sera Abs specific for core xylose, whereas 25% have Abs against core alpha(1,3)-fucose. These Abs probably result from sensitization to environmental antigens. Although the immunological significance of these data is too speculative at the moment, the presence of such Abs might introduce some limitations to the use of plant-derived biopharmaceutical glycoproteins, such as an accelerated clearance during human therapy.
Bardor
Muriel
M
CNRS-UMR 6037, IFRMP 23, Université de Rouen, 76821 Mont Saint Aignan Cédex, France.
Faveeuw
Christelle
C
Fitchette
Anne-Catherine
AC
Gilbert
Danièle
D
Galas
Ludovic
L
Trottein
Francois
F
Faye
Loïc
L
Lerouge
Patrice
P
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002240:Carbohydrate Sequence; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D005643:Fucose / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology* / Q000627:therapeutic use; D006735:Horseradish Peroxidase / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008322:Mammals / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012275:Oryza / Q000737:chemistry / Q000276:immunology; D018532:Pisum sativum / Q000737:chemistry / Q000276:immunology; D010944:Plants / Q000737:chemistry* / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D014994:Xylose / Q000276:immunology*; D003313:Zea mays / Q000737:chemistry / Q000276:immunology
D000906:Antibodies; D000939:Epitopes; D006023:Glycoproteins; D007106:Immune Sera; D005643:Fucose; D014994:Xylose; D006735:Horseradish Peroxidase