Improved virus neutralization by plant-produced anti-HIV antibodies with a homogeneous beta1,4-galactosylated N-glycan profile.
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 beta1,4-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 beta1,4-galactosyltransferase in glycoengineered plants lacking plant-specific glycosylation. Moreover, we demonstrate that two anti-human immunodeficiency virus mAbs with fully beta1,4-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.
Strasser
Richard
R
Department of Applied Genetics and Cell Biology, University of Natural Resources and Applied Life Sciences, 1190 Vienna, Austria.
Castilho
Alexandra
A
Stadlmann
Johannes
J
Kunert
Renate
R
Quendler
Heribert
H
Gattinger
Pia
P
Jez
Jakub
J
Rademacher
Thomas
T
Altmann
Friedrich
F
Mach
Lukas
L
Steinkellner
Herta
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003433:Crosses, Genetic; D005690:Galactose / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics; D006031:Glycosylation; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009154:Mutation / Q000235:genetics; D009500:Neutralization Tests; D046549:Plantibodies / Q000276:immunology*; D011134:Polysaccharides / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D014026:Nicotiana / Q000235:genetics / Q000378:metabolism; D014170:Transformation, Genetic
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D046549:Plantibodies; D011134:Polysaccharides; D020033:Protein Isoforms; D005690:Galactose