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

Autor: Stelter S; Hotung Molecular Immunology Unit, Institute for Infection and Immunity, St George's University of London, London, UK., Paul MJ; Hotung Molecular Immunology Unit, Institute for Infection and Immunity, St George's University of London, London, UK., Teh AY; Hotung Molecular Immunology Unit, Institute for Infection and Immunity, St George's University of London, London, UK., Grandits M; Hotung Molecular Immunology Unit, Institute for Infection and Immunity, St George's University of London, London, UK., Altmann F; Division of Biochemistry, University of Natural Resources and Life Sciences, Vienna, Austria., Vanier J; UNIROUEN, Laboratoire Glycobiologie et Matrice Extracellulaire Végétale EA, Normandie Univ, Rouen, France., Bardor M; UNIROUEN, Laboratoire Glycobiologie et Matrice Extracellulaire Végétale EA, Normandie Univ, Rouen, France.; Institut Universitaire de France (I.U.F.), Paris Cedex 05, France., Castilho A; Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria., Allen RL; Institute for Infection and Immunity, St George's University of London, London, UK., Ma JK; Hotung Molecular Immunology Unit, Institute for Infection and Immunity, St George's University of London, London, UK.
Jazyk: angličtina
Zdroj: Plant biotechnology journal [Plant Biotechnol J] 2020 Feb; Vol. 18 (2), pp. 402-414. Date of Electronic Publication: 2019 Aug 10.
DOI: 10.1111/pbi.13207
Abstrakt: 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 α1,3-fucose and β1,2-xylose residues and glycans extended with terminal β1,4-galactose. Surface plasmon resonance-based assays were established for kinetic/affinity evaluation of antibody-FcγR interactions, and revealed that antibodies with typical plant glycosylation have a limited capacity to engage FcγRI, FcγRIIa, FcγRIIb and FcγRIIIa; 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.
(© 2019 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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