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

• DOI: 10.1099/jgv.0.000635
• Publication Date: 2016-10-21T17:23:57Z
• Authors: Matthew Dent; Jonathan Hurtado; Amber M. Paul; Haiyan Sun; Huafang Lai; Ming Yang; Adrian Esqueda; Fengwei Bai; Herta Steinkellner; Qiang Chen
• Keywords: Antibody-dependent enhancement

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