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Gewählte Publikation:

Strasser, R; Castilho, A; Stadlmann, J; Kunert, R; Quendler, H; Gattinger, P; Jez, J; Rademacher, T; Altmann, F; Mach, L; Steinkellner, H.
(2009): Improved virus neutralization by plant-produced anti-HIV antibodies with a homogeneous beta1,4-galactosylated N-glycan profile.
J Biol Chem. 2009; 284(31):20479-20485 FullText FullText_BOKU

Abstract:
It is well established that proper N-glycosylation significantly influences the efficacy of monoclonal antibodies (mAbs). However, the specific immunological relevance of individual mAb-associated N-glycan structures is currently largely unknown, because of the heterogeneous N-glycan profiles of mAbs when produced in mammalian cells. Here we report on the generation of a plant-based expression platform allowing the efficient production of mAbs with a homogeneous beta 1,4-galactosylated N-glycosylation structure, the major N-glycan species present on serum IgG. This was achieved by the expression of a highly active modified version of the human beta 1,4-galactosyl-transferase in glycoengineered plants lacking plant-specific glycosylation. Moreover, we demonstrate that two anti-human immunodeficiency virus mAbs with fully beta 1,4-galactosylated N-glycans display improved virus neutralization potency when compared with other glycoforms produced in plants and Chinese hamster ovary cells. These findings indicate that mAbs containing such homogeneous N-glycan structures should display improved in vivo activities. Our system, using expression of mAbs in tobacco plants engineered for post-translational protein processing, provides a new means of overcoming the two hurdles that limit the therapeutic use of anti-human immunodeficiency virus mAbs in global health initiatives, low biological potency and high production costs.
Autor*innen der BOKU Wien:
Altmann Friedrich
De Vitoria Pereira Alexandra
Gattinger Pia Simone
Kunert Renate
Mach Lukas
Quendler Heribert
Stadlmann Johannes
Steinkellner Herta
Strasser Richard
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Find related publications in this database (using NML MeSH Indexing)
Animals -
Antibodies, Monoclonal - biosynthesis
CHO Cells -
Cell Line -
Cricetinae -
Cricetulus -
Crosses, Genetic -
Galactose - metabolism
Genetic Vectors - genetics
Glycosylation -
HIV Antibodies - biosynthesis
HIV-1 - immunology
Humans -
Mutation - genetics
Neutralization Tests -
Plantibodies - immunology
Polysaccharides - metabolism
Protein Isoforms - chemistry
Rats -
Tobacco - genetics
Transformation, Genetic -



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