Function and glycosylation of plant-derived antiviral monoclonal antibody
Function and glycosylation of plant-derived antiviral monoclonal antibody
复制标题
DOI：
10.1073/pnas.0832472100
复制
发表时间：
2003-06-24
影响因子：
11.1
通讯作者：
Koprowski, H
中科院分区：
文献类型：
--
作者：
Ko, KS;Tekoah, Y;Koprowski, H
植物基因工程导致了植物来源的mAb（mAb（P））的产生，其为当前在动物系统中产生抗体的方法提供了安全且经济可行的替代方案。在本研究中，在两个强组成型启动子的控制下，在植物中表达和组装人抗狂犬病单克隆抗体的重链和轻链。苜蓿花叶病毒非翻译前导序列和Lys-Asp-Glu-Leu（KDEL）内质网滞留信号分别连接在重链的N端和C端。mAbP在中和狂犬病病毒活性方面与人源性抗体（mAb（M））或人狂犬病IG（HRIG）一样有效。mAb（P）主要含有寡聚甘露糖型N-聚糖（90%），无潜在抗原性α（1，3）-连接岩藻糖残基。mAb（P）的半衰期比mAb（M）短。mAb（P）与HRIG在仓鼠中暴露后预防狂犬病病毒方面同样有效，表明N-糖基化差异不影响该模型中抗体的有效性。
Plant genetic engineering led to the production of plant-derived mAb (mAb(P)), 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 (mAb(M)) or human rabies Ig (HRIG). The mAb(P) contained mainly oligomannose type N-glycans (90%) and had no potentially antigenic alpha(1,3)-linked fucose residues. mAb(P) had a shorter half-life than mAb(M). The mAb(P) 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.