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Engineering the interactions between a plant-produced HIV antibody and human Fc receptors.


ABSTRACT: Plants can provide a cost-effective and scalable technology for production of therapeutic monoclonal antibodies, with the potential for precise engineering of glycosylation. Glycan structures in the antibody Fc region influence binding properties to Fc receptors, which opens opportunities for modulation of antibody effector functions. To test the impact of glycosylation in detail, on binding to human Fc receptors, different glycovariants of VRC01, a broadly neutralizing HIV monoclonal antibody, were generated in Nicotiana benthamiana and characterized. These include glycovariants lacking plant characteristic ?1,3-fucose and ?1,2-xylose residues and glycans extended with terminal ?1,4-galactose. Surface plasmon resonance-based assays were established for kinetic/affinity evaluation of antibody-Fc?R interactions, and revealed that antibodies with typical plant glycosylation have a limited capacity to engage Fc?RI, Fc?RIIa, Fc?RIIb and Fc?RIIIa; however, the binding characteristics can be restored and even improved with targeted glycoengineering. All plant-made glycovariants had a slightly reduced affinity to the neonatal Fc receptor (FcRn) compared with HEK cell-derived antibody. However, this was independent of plant glycosylation, but related to the oxidation status of two methionine residues in the Fc region. This points towards a need for process optimization to control oxidation levels and improve the quality of plant-produced antibodies.

SUBMITTER: Stelter S 

PROVIDER: S-EPMC6953194 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Engineering the interactions between a plant-produced HIV antibody and human Fc receptors.

Stelter Szymon S   Paul Mathew J MJ   Teh Audrey Y-H AY   Grandits Melanie M   Altmann Friedrich F   Vanier Jessica J   Bardor Muriel M   Castilho Alexandra A   Allen Rachel Louise RL   Ma Julian K-C JK  

Plant biotechnology journal 20190810 2


Plants can provide a cost-effective and scalable technology for production of therapeutic monoclonal antibodies, with the potential for precise engineering of glycosylation. Glycan structures in the antibody Fc region influence binding properties to Fc receptors, which opens opportunities for modulation of antibody effector functions. To test the impact of glycosylation in detail, on binding to human Fc receptors, different glycovariants of VRC01, a broadly neutralizing HIV monoclonal antibody,  ...[more]

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