Increased in vitro neutralizing activity of SARS-CoV-2 IgA1 dimers compared to monomers and IgG.
basic_science · Level V
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- Record sourced from PubMed, PMID 34702738.
- Also identified by DOI 10.1073/pnas.2107148118 and PMC identifier 8612245.
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Abstract
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 <i>Nicotiana benthamiana</i> 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.
Medical subject headings
- Antibodies, Monoclonal
- COVID-19
- Immunoglobulin A
- Immunoglobulin G
- SARS-CoV-2