A Monoclonal Antibody Produced in Glycoengineered Plants Potently Neutralizes Monkeypox Virus

The 2022 global outbreaks of monkeypox virus (MPXV) and increased human-to-human transmission calls for the urgent development of countermeasures to protect people who cannot benefit from vaccination. Here, we describe the development of glycovariants of 7D11, a neutralizing monoclonal IgG antibody (mAb) directed against the L1 transmembrane protein of the related vaccinia virus, in a plant-based system as a potential therapeutic against the current MPVX outbreak. Our results indicated that 7D11 mAb quickly accumulates to high levels within a week after gene introduction to plants. Plant-produced 7D11 mAb assembled correctly into the tetrameric IgG structure and can be easily purified to homogeneity. 7D11 mAb exhibited a largely homogeneous N-glycosylation profile, with or without plant-specific xylose and fucose residues, depending on the expression host, namely wild-type or glycoengineered plants. Plant-made 7D11 retained specific binding to its antigen and displayed a strong neutralization activity against MPXV, as least as potent as the reported activity against vaccinia virus. Our study highlights the utility of anti-L1 mAbs as MPXV therapeutics, and the use of glycoengineered plants to develop mAb glycovariants for potentially enhancing the efficacy of mAbs to combat ever-emerging/re-emerging viral diseases.

Automated summary

The development of glycovariants of 7D11, a neutralizing monoclonal antibody, produced in plants, shows promise as a potential therapeutic against the current monkeypox virus (MPXV) outbreak. The plant-made 7D11 antibody quickly accumulates to high levels and can be easily purified. It retains specific binding to its antigen and displays strong neutralization activity against MPXV, similar to its activity against vaccinia virus.