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

18 Scopus 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 2016

Keywords

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

ASJC Scopus subject areas

  • Virology

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    Dent, M., Hurtado, J., Paul, A. M., 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, 97(12), 3280-3290. [000635]. https://doi.org/10.1099/jgv.0.000635