Authors

Jeong-Hwan Lee, Department of Medicine, Medical Research Institute, College of Medicine, Chung-Ang University
Da-Young Park, Department of Medicine, Medical Research Institute, College of Medicine, Chung-Ang University
Kyung-Jin Lee, Department of Medicine, Medical Research Institute, College of Medicine, Chung-Ang University
Young-Kwan Kim, Department of Herbology, School of Oriental Medicine, Wonkwang University
Yang-Kang So, Department of Medicine, Medical Research Institute, College of Medicine, Chung-Ang University
Jae-Sung Ryu, Department of Biological Science, Biotechnology Institute, College of Natural Science, Wonkwang University
Seung-Han Oh, Department of Agricultural Biology, College of Agriculture and Life Science, Chonnam National University
Yeon-Soo Han, Department of Agricultural Biology, College of Agriculture and Life Science, Chonnam National University
Kinarm Ko, Department of Neuroscience, School of Medicine, Konkuk University
Young-Kug Choo, Department of Biological Science, Biotechnology Institute, College of Natural Science, Wonkwang University
Sung-Joo Park, Department of Herbology, School of Oriental Medicine, Wonkwang University
Robert Brodzik, Biotechnology Foundation Laboratories, Thomas Jefferson University
Kyoung-Ki Lee, National Veterinary Research and Quarantine Service
Doo-Byoung Oh, Korean Research Institute of Bioscience and Biotechnology
Kyung-A Hwang, Department of Agrofood Resources, National Academy of Agricultural Science
Hilary Koprowski, Biotechnology Foundation Laboratories, Thomas Jefferson UniversityFollow
Yong Seong Lee, Department of Urology, College of Medicine, Kangnam Sacred Heart Hospital, Hallym University
Kisung Ko, Department of Medicine, Medical Research Institute, College of Medicine, Chung-Ang University

Document Type

Article

Publication Date

8-15-2013

Comments

This article has been peer reviewed. It was published in: PLoS One.
Volume 8, Issue 8, 15 August 2013, Article number e68772.
The published version is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744537/?report=classic. DOI: 10.1371/journal.pone.0068772

Copyright © 2013 Lee et al.

Abstract

Plant genetic engineering, which has led to the production of plant-derived monoclonal antibodies (mAb(P)s), provides a safe and economically effective alternative to conventional antibody expression methods. In this study, the expression levels and biological properties of the anti-rabies virus mAb(P) SO57 with or without an endoplasmic reticulum (ER)-retention peptide signal (Lys-Asp-Glu-Leu; KDEL) in transgenic tobacco plants (Nicotiana tabacum) were analyzed. The expression levels of mAb(P) SO57 with KDEL (mAb(P)K) were significantly higher than those of mAb(P) SO57 without KDEL (mAb(P)) regardless of the transcription level. The Fc domains of both purified mAb(P) and mAb(P)K and hybridoma-derived mAb (mAb(H)) had similar levels of binding activity to the FcγRI receptor (CD64). The mAb(P)K had glycan profiles of both oligomannose (OM) type (91.7%) and Golgi type (8.3%), whereas the mAb(P) had mainly Golgi type glycans (96.8%) similar to those seen with mAb(H). Confocal analysis showed that the mAb(P)K was co-localized to ER-tracker signal and cellular areas surrounding the nucleus indicating accumulation of the mAb(P) with KDEL in the ER. Both mAb(P) and mAb(P)K disappeared with similar trends to mAb(H) in BALB/c mice. In addition, mAb(P)K was as effective as mAb(H) at neutralizing the activity of the rabies virus CVS-11. These results suggest that the ER localization of the recombinant mAb(P) by KDEL reprograms OM glycosylation and enhances the production of the functional antivirus therapeutic antibody in the plant.

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