Plant-produced anti-dengue virus monoclonal antibodies exhibit reduced antibody-dependent enhancement of infection activity

Matthew Dent, Jonathan Hurtado, Amber M. Paul, Haiyan Sun, Huafang Lai, Ming Yang, Adrian Esqueda, Fengwei Bai, Herta Steinkellner, Qiang Chen

Research output: Contribution to journalArticle

  • 2 Citations

Abstract

The mAb E60 has the potential to be a desirable therapeutic molecule since it efficiently neutralizes all four serotypes of dengue virus (DENV). However, mammalian-cell-produced E60 exhibits antibody-dependent enhancement of infection (ADE) activity, rendering it inefficacious in vivo, and treated animals more susceptible to developing more severe diseases during secondary infection. In this study, we evaluated a plant-based expression system for the production of therapeutically suitable E60. The mAb was transiently expressed in Nicotiana benthamianaWT and a ∆XFT line, a glycosylation mutant lacking plant-specific N-glycan residues. The mAb was efficiently expressed and assembled in leaves and exhibited highly homogenous N-glycosylation profiles, i.e. GnGnXF3 or GnGn structures, depending on the expression host. Both E60 glycovariants demonstrated equivalent antigen-binding specificity and in vitro neutralization potency against DENV serotypes 2 and 4 compared with their mammalian-cell-produced counterpart. By contrast, plant-produced E60 exhibited reduced ADE activity in Fc gamma receptor expressing human cells. Our results suggest the ability of plant-produced antibodies to minimize ADE, which may lead to the development of safe and highly efficacious antibody-based therapeutics against DENV and other ADE-prone viral diseases. Our study provides so far unknown insight into the relationship between mAb N-glycosylation and ADE, which contributes to our understanding of how sugar moieties of antibodies modulate Fc-mediated functions and viral pathogenesis.

Original languageEnglish (US)
Article number000635
Pages (from-to)3280-3290
Number of pages11
JournalJournal of General Virology
Volume97
Issue number12
DOIs
StatePublished - Dec 1 2016

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Antibody-Dependent Enhancement
Dengue Virus
Monoclonal Antibodies
Infection
Glycosylation
Antibodies
Serogroup
IgG Receptors
Virus Diseases
Coinfection
Tobacco
Polysaccharides
Carbohydrates
Antigens
In Vitro Techniques

Keywords

  • Antibody-dependent enhancement (ADE)
  • Dengue virus
  • Fc receptors
  • Glycosylation
  • Monoclonal antibody
  • Plant-made therapeutics

ASJC Scopus subject areas

  • Virology

Cite this

Plant-produced anti-dengue virus monoclonal antibodies exhibit reduced antibody-dependent enhancement of infection activity. / Dent, Matthew; Hurtado, Jonathan; Paul, Amber M.; Sun, Haiyan; Lai, Huafang; Yang, Ming; Esqueda, Adrian; Bai, Fengwei; Steinkellner, Herta; Chen, Qiang.

In: Journal of General Virology, Vol. 97, No. 12, 000635, 01.12.2016, p. 3280-3290.

Research output: Contribution to journalArticle

Dent, M, Hurtado, J, Paul, AM, Sun, H, Lai, H, Yang, M, Esqueda, A, Bai, F, Steinkellner, H & Chen, Q 2016, 'Plant-produced anti-dengue virus monoclonal antibodies exhibit reduced antibody-dependent enhancement of infection activity' Journal of General Virology, vol 97, no. 12, 000635, pp. 3280-3290. DOI: 10.1099/jgv.0.000635
Dent M, Hurtado J, Paul AM, Sun H, Lai H, Yang M et al. Plant-produced anti-dengue virus monoclonal antibodies exhibit reduced antibody-dependent enhancement of infection activity. Journal of General Virology. 2016 Dec 1;97(12):3280-3290. 000635. Available from, DOI: 10.1099/jgv.0.000635

Dent, Matthew; Hurtado, Jonathan; Paul, Amber M.; Sun, Haiyan; Lai, Huafang; Yang, Ming; Esqueda, Adrian; Bai, Fengwei; Steinkellner, Herta; Chen, Qiang / Plant-produced anti-dengue virus monoclonal antibodies exhibit reduced antibody-dependent enhancement of infection activity.

In: Journal of General Virology, Vol. 97, No. 12, 000635, 01.12.2016, p. 3280-3290.

Research output: Contribution to journalArticle

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