BOKU - Universität für Bodenkultur Wien - Forschungsinformationssystem
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
- BOKU Gendermonitor:
- 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 -
Altmetric: