Function and glycosylation of plant-derived antiviral monoclonal antibody.
Plant genetic engineering led to the production of plant-derived mAb (mAbP), which provides a safe and economically feasible alternative to the current methods of antibody production in animal systems. In this study, the heavy and light chains of human anti-rabies mAb were expressed and assembled in planta under the control of two strong constitutive promoters. An alfalfa mosaic virus untranslated leader sequence and Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum retention signal were linked at the N and C terminus of the heavy chain, respectively. mAbP was as effective at neutralizing the activity of the rabies virus as the mammalian-derived antibody (mAbM) or human rabies Ig (HRIG). The mAbP contained mainly oligomannose type N-glycans (90%) and had no potentially antigenic alpha(1,3)-linked fucose residues. mAbP had a shorter half-life than mAbM. The mAbP was as efficient as HRIG for post-exposure prophylaxis against rabies virus in hamsters, indicating that differences in N-glycosylation do not affect the efficacy of the antibody in this model.
Ko
Kisung
K
Biotechnology Foundation Laboratories at Thomas Jefferson University, 1020 Locust Street, JAH, Philadelphia, PA 19107, USA.
Tekoah
Yoram
Y
Rudd
Pauline M
PM
Harvey
David J
DJ
Dwek
Raymond A
RA
Spitsin
Sergei
S
Hanlon
Cathleen A
CA
Rupprecht
Charles
C
Dietzschold
Bernhard
B
Golovkin
Maxim
M
Koprowski
Hilary
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017343:Genes, Plant; D006031:Glycosylation; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D008957:Models, Genetic; D008969:Molecular Sequence Data; D030821:Plants, Genetically Modified; D011134:Polysaccharides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011820:Rabies virus / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D014026:Nicotiana / Q000235:genetics
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D011134:Polysaccharides