Open AccessIncreased in vitro neutralizing activity of SARS-CoV-2 IgA1 dimers compared to monomers and IgG
Author(s) -
Lin Sun,
Somanath Kallolimath,
Roman Palt,
Karin Stiasny,
Patrick Mayrhofer,
Daniel Maresch,
Lukas Eidenberger,
Herta Steinkellner
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2107148118
Subject(s) - potency , neutralization , glycosylation , nicotiana benthamiana , antibody , in vitro , chemistry , antigen , monoclonal antibody , monomer , immunoglobulin fab fragments , virology , biology , microbiology and biotechnology , immunology , biochemistry , complementarity determining region , gene , organic chemistry , polymer
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 glycoengineeredNicotiana 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.