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Highly active engineered IgG3 antibodies against SARS-CoV-2


Posted: 2021-10-02 19:00:00
Proc Natl Acad Sci U S A . 2021 Oct 1;118(42):e2107249118. doi: 10.1073/pnas.2107249118. Affiliations Expand Affiliations 1 Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, 1180 Vienna, Austria. 2 Center for Virology, Medical University of Vienna, 1090 Vienna, Austria. 3 Department of Biotechnology, University of Natural Resources and Life Sciences, 1180 Vienna, Austria. 4 Core Facility Mass Spectrometry, University of Natural Resources and Life Sciences, 1180 Vienna, Austria. 5 The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ 85281. 6 Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, 1180 Vienna, Austria; herta.steinkellner@boku.ac.at. Item in Clipboard Somanath Kallolimath et al. Proc Natl Acad Sci U S A. 2021. Show details Display options Display options Format Proc Natl Acad Sci U S A . 2021 Oct 1;118(42):e2107249118. doi: 10.1073/pnas.2107249118. Affiliations 1 Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, 1180 Vienna, Austria. 2 Center for Virology, Medical University of Vienna, 1090 Vienna, Austria. 3 Department of Biotechnology, University of Natural Resources and Life Sciences, 1180 Vienna, Austria. 4 Core Facility Mass Spectrometry, University of Natural Resources and Life Sciences, 1180 Vienna, Austria. 5 The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ 85281. 6 Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, 1180 Vienna, Austria; herta.steinkellner@boku.ac.at. Item in Clipboard CiteDisplay options Display options Format 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. Keywords: SARS-CoV-2; antibodies; engineered IgG3; plant-based expression; virus neutralization. Copyright © 2021 the Author(s). Published by PNAS. Conflict of interest statement The authors declare no competing interest. References Wu Y., et al. A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2. Science. 2020;368:1274–1278. Amanat F., et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat. Med.. 2020;26:1033–1036. Atyeo C., et al. Dissecting strategies to tune the therapeutic potential of SARS-CoV-2-specific monoclonal antibody CR3022. JCI Insight. 2021;6:143129. Liu L., et al. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight. 2019;4:123158. Kallolimath S., et al. Expression profiling and glycan engineering of IgG subclass 1-4 in Nicotiana benthamiana. Front. Bioeng. Biotechnol.. 2020;8:825. Show all 14 references [x] Cite Copy Format: Send To [x]

参考サイト PubMed: covid-19



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