Increased in vitro neutralizing activity of SARS-CoV-2 IgA1 dimers compared to monomers and IgG

Here, we expressed two neutralizing monoclonal antibodies (Abs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; H4 and B38) in three formats: IgG1, IgA1 monomers (m), and IgA1 dimers (d) in glycoengineered Nicotiana benthamiana plants. All six Ab variants assembled properly and exhibited a largely homogeneous glycosylation profile. Despite modest variation in antigen binding between Ab formats, SARS-CoV-2 neutralization (NT) potency significantly increased in the following manner: IgG1 < IgA1-m < IgA1-d, with an up to 240-fold NT increase of dimers compared to corresponding monomers. Our results underscore that both IgA's structural features and multivalency positively impact NT potency. In addition, they emphasize the versatile use of plants for the rapid expression of complex human proteins.

Automated summary

In this study, two neutralizing monoclonal antibodies against SARS-CoV-2 were expressed in glycoengineered Nicotiana benthamiana plants in three formats. The IgA1 dimers showed a significantly higher neutralization potency than monomers, indicating the positive impact of IgA structural features and multivalency on neutralization potency. Additionally, the study highlighted the versatile use of plants for rapid expression of complex human proteins.