TY - JOUR
T1 - Highly active engineered IgG3 antibodies against SARS-CoV-2
AU - Kallolimath, Somanath
AU - Sun, Lin
AU - Palt, Roman
AU - Stiasny, Karin
AU - Mayrhofer, Patrick
AU - Gruber, Clemens
AU - Kogelmann, Benjamin
AU - Chen, Qiang
AU - Steinkellner, Herta
N1 - Funding Information:
ACKNOWLEDGMENTS. We thank Jutta Hutecek (Center for Virology, Medical University of Vienna) for excellent technical assistance and Victor Klimyuk (Icon Genetics GmbH) for providing MagnICON vectors TMVα and PVXα. This work was supported by Austrian Science Fund Grants I 4328-B and I 3721-B30 (to H.S.) and the BOKU COVID-19 Initiative.
Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.
PY - 2021/10/19
Y1 - 2021/10/19
N2 - 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.
AB - 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.
KW - Antibodies
KW - Engineered IgG3
KW - Plant-based expression
KW - SARS-CoV-2
KW - Virus neutralization
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U2 - 10.1073/pnas.2107249118
DO - 10.1073/pnas.2107249118
M3 - Article
C2 - 34599091
AN - SCOPUS:85116992080
SN - 0027-8424
VL - 118
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 42
M1 - e2107249118
ER -