In vitro and in vivo efficacy of anti-chikungunya virus monoclonal antibodies produced in wild-type and glycoengineered Nicotiana benthamiana plants

Jonathan Hurtado, Dhiraj Acharya, Huafang Lai, Haiyan Sun, Somanath Kallolimath, Herta Steinkellner, Fengwei Bai, Qiang Chen

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus, and its infection can cause long-term debilitating arthritis in humans. Currently, there are no licensed vaccines or therapeutics for human use to combat CHIKV infections. In this study, we explored the feasibility of using an anti-CHIKV monoclonal antibody (mAb) produced in wild-type (WT) and glycoengineered (∆XFT) Nicotiana benthamiana plants in treating CHIKV infection in a mouse model. CHIKV mAb was efficiently expressed and assembled in plant leaves and enriched to homogeneity by a simple purification scheme. While mAb produced in ∆XFT carried a single N-glycan species at the Fc domain, namely GnGn structures, WT produced mAb exhibited a mixture of N-glycans including the typical plant GnGnXF3 glycans, accompanied by incompletely processed and oligomannosidic structures. Both WT and ∆XFT plant-produced mAbs demonstrated potent in vitro neutralization activity against CHIKV. Notably, both mAb glycoforms showed in vivo efficacy in a mouse model, with a slight increased efficacy by the ∆XFT-produced mAbs. This is the first report of the efficacy of plant-produced mAbs against CHIKV, which demonstrates the ability of using plants as an effective platform for production of functionally active CHIKV mAbs and implies optimization of in vivo activity by controlling Fc glycosylation.

Original languageEnglish (US)
JournalPlant Biotechnology Journal
DOIs
StatePublished - Jan 1 2019

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Chikungunya virus
Nicotiana benthamiana
Tobacco
monoclonal antibodies
Monoclonal Antibodies
Polysaccharides
Alphavirus Infections
polysaccharides
Plant Leaves
animal models
Therapeutic Uses
infection
Alphavirus
Culicidae
Glycosylation
Arthritis
In Vitro Techniques
arthritis
Vaccines
glycosylation

Keywords

  • chikungunya virus
  • glycoengineering
  • glycosylation
  • monoclonal antibody
  • neutralization
  • plant-made antibody
  • plant-made therapeutics

ASJC Scopus subject areas

  • Biotechnology
  • Agronomy and Crop Science
  • Plant Science

Cite this

In vitro and in vivo efficacy of anti-chikungunya virus monoclonal antibodies produced in wild-type and glycoengineered Nicotiana benthamiana plants. / Hurtado, Jonathan; Acharya, Dhiraj; Lai, Huafang; Sun, Haiyan; Kallolimath, Somanath; Steinkellner, Herta; Bai, Fengwei; Chen, Qiang.

In: Plant Biotechnology Journal, 01.01.2019.

Research output: Contribution to journalArticle

Hurtado, Jonathan ; Acharya, Dhiraj ; Lai, Huafang ; Sun, Haiyan ; Kallolimath, Somanath ; Steinkellner, Herta ; Bai, Fengwei ; Chen, Qiang. / In vitro and in vivo efficacy of anti-chikungunya virus monoclonal antibodies produced in wild-type and glycoengineered Nicotiana benthamiana plants. In: Plant Biotechnology Journal. 2019.
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