Glycan immunogenicity

The following sections describe several examples of saccharide modification for the purpose of bioconjugation, the study of glycan function, to prepare immunogens, or to increase the water solubility of a modified molecule. 

Plant-made Pharmaceuticals Possess Immunogenic N-glycans 241... 

Plants are not the only heterogeneous expression system to produce potentially immunogenic N-glycans. When antibodies are produced in non-human mammalian... 

Current Strategies to Eliminate Immunogenic N-glycans from Plant-made Pharmaceuticals... 

Similar results were recently obtained with a human monoclonal antibody, with KDEL sequences fused to the C-termini of both heavy chains, expressed in tobacco [33]. As observed for the invertase-HDEL fusion, about 90% of the N-linked glycans on this antibody were of the high-mannose type, with 6-9 mannose residues, while a fraction contained the immunogenic P(l,2)-xylose glyco-epitope (Fig. 15.6). However, this antibody was not a(l,3)-fucosylated, a glycan modification occurring in the trans Golgi [34]. 

Koprivova A, Stemmer C, Altmann F, Hoffmann A, Kopriva S, Gorr G Reski R, Decker EL. (2004) Targeted knockouts of Physcomitrella lacking plant-specific immunogenic A-glycans. Plant Biotechnol J 2 517-523. 

Another way that P(l,2)-linked xylose can be removed from plant proteins involves the use of P(l,2)-xylosidase. This is a degradative enzyme that is easily prepared from potatoes. If the 3-position of this maimose is not occupied, P(l,2)-xylosidase releases xylose residues that are P(l,2)-linked to the heta-mannose of an A-glycan core. This techiuque can also be applied to plant-derived therapeutic glycoproteins to remove potential immunogenic epitopes (Lerouge et al., 1998). 

Chargelegue, D Vine, N.D., van Dolleweerd, C.J., Drake, P.M., and Ma, J.K. (2000). A murine monoclonal antibody produced in transgenic plants with plant-specific glycans is not immunogenic in mice. Transgenic Res. 9 187-194. 

The anti-S. faecalis antiserum reacted with Lac-BSA amd the glycan as shown in the bottom panels of Figure 8. The amti-lac antibodies from this serum also reacted with these two immunogens yielding a similar pattern as the unfractionated amtiserum. It should be noted that the amtiserum amd amtibody preparations exhibited partial identity with these two antigens. The anti-gal antibodies also reacted with Lac-BSA amd the glycan but the precipitin bamds were quite different. 

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