Highly active engineered IgG3 antibodies against SARS-CoV-2

Somanath Kallolimath, Lin Sun, Roman Palt, Karin Stiasny, Patrick Mayrhofer, Clemens Gruber, Benjamin Kogelmann, Qiang Chen, Herta Steinkellner

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Monoclonal antibodies (mAbs) that efficiently neutralize SARS-CoV-2 have been developed at an unprecedented speed. Notwithstanding, there is a vague understanding of the various Ab functions induced beyond antigen binding by the heavy-chain constant domain. To explore the diverse roles of Abs in SARS-CoV-2 immunity, we expressed a SARS-CoV-2 spike protein (SP) binding mAb (H4) in the four IgG subclasses present in human serum (IgG1-4) using glyco-engineered Nicotiana benthamiana plants. All four subclasses, carrying the identical antigen-binding site, were fully assembled in planta and exhibited a largely homogeneous xylose- and fucose-free glycosylation profile. The Ab variants ligated to the SP with an up to fivefold increased binding activity of IgG3. Furthermore, all H4 subtypes were able to neutralize SARS-CoV-2. However, H4-IgG3 exhibited an up to 50-fold superior neutralization potency compared with the other subclasses. Our data point to a strong protective effect of IgG3 Abs in SARS-CoV-2 infection and suggest that superior neutralization might be a consequence of cross-linking the SP on the viral surface. This should be considered in therapy and vaccine development. In addition, we underscore the versatile use of plants for the rapid expression of complex proteins in emergency cases.

Original languageEnglish (US)
Article numbere2107249118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number42
DOIs
StatePublished - Oct 19 2021
Externally publishedYes

Keywords

  • Antibodies
  • Engineered IgG3
  • Plant-based expression
  • SARS-CoV-2
  • Virus neutralization

ASJC Scopus subject areas

  • General

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