Peter, Antonia Sophia and Roth, Edith and Schulz, Sebastian R. and Fraedrich, Kirsten and Steinmetz, Tobit and Damm, Dominik and Hauke, Manuela and Richel, Elie and Mueller-Schmucker, Sandra and Habenicht, Katharina and Eberlein, Valentina and Issmail, Leila and Uhlig, Nadja and Dolles, Simon and Grüner, Eva and Peterhoff, David and Ciesek, Sandra and Hoffmann, Markus and Pöhlmann, Stefan and McKay, Paul F. and Shattock, Robin J. and Wölfel, Roman and Socher, Eileen and Wagner, Ralf and Eichler, Jutta and Sticht, Heinrich and Schuh, Wolfgang and Neipel, Frank and Ensser, Armin and Mielenz, Dirk and Tenbusch, Matthias and Winkler, Thomas H. and Grunwald, Thomas and Überla, Klaus and Jäck, Hans-Martin (2022) A pair of noncompeting neutralizing human monoclonal antibodies protecting from disease in a SARS-CoV-2 infection model. EUROPEAN JOURNAL OF IMMUNOLOGY, 52 (5). pp. 770-783. ISSN 0014-2980, 1521-4141
Full text not available from this repository. (Request a copy)Abstract
TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly isolate human monoclonal antibodies. After immunizing these mice with DNA encoding the spike protein of SARS-CoV-2 and boosting with spike protein, we identified 29 hybridoma antibodies that reacted with the SARS-CoV-2 spike protein. Nine antibodies neutralize SARS-CoV-2 infection at IC50 values in the subnanomolar range. ELISA-binding studies and DNA sequence analyses revealed one cluster of three clonally related neutralizing antibodies that target the receptor-binding domain and compete with the cellular receptor hACE2. A second cluster of six clonally related neutralizing antibodies bind to the N-terminal domain of the spike protein without competing with the binding of hACE2 or cluster 1 antibodies. SARS-CoV-2 mutants selected for resistance to an antibody from one cluster are still neutralized by an antibody from the other cluster. Antibodies from both clusters markedly reduced viral spread in mice transgenic for human ACE2 and protected the animals from SARS-CoV-2-induced weight loss. The two clusters of potent noncompeting SARS-CoV-2 neutralizing antibodies provide potential candidates for therapy and prophylaxis of COVID-19. The study further supports transgenic animals with a human immunoglobulin gene repertoire as a powerful platform in pandemic preparedness initiatives.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CELL; EVOLUTION; BROAD; SPIKE; COVID-19; neutralizing antibodies; spike protein; SARS-CoV-2; variants of concern |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Petra Gürster |
| Date Deposited: | 01 Feb 2023 13:29 |
| Last Modified: | 01 Feb 2023 13:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47779 |
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