RT Journal Article SR Electronic(1) A1 Dent, Matthew A1 Hurtado, Jonathan A1 Paul, Amber M. A1 Sun, Haiyan A1 Lai, Huafang A1 Yang, Ming A1 Esqueda, Adrian A1 Bai, Fengwei A1 Steinkellner, Herta A1 Chen, QiangYR 2016 T1 Plant-produced anti-dengue virus monoclonal antibodies exhibit reduced antibody-dependent enhancement of infection activity JF Journal of General Virology, VO 97 IS 12 SP 3280 OP 3290 DO https://doi.org/10.1099/jgv.0.000635 PB Microbiology Society, SN 1465-2099, AB 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., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000635