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Peter, Antonia Sophia ; Roth, Edith ; Schulz, Sebastian R. ; Fraedrich, Kirsten ; Steinmetz, Tobit ; Damm, Dominik ; Hauke, Manuela ; Richel, Elie ; Müller-Schmucker, Sandra ; Habenicht, Katharina ; Eberlein, Valentina ; Issmail, Leila ; Uhlig, Nadja ; Dolles, Simon ; Grüner, Eva ; Peterhoff, David ; Ciesek, Sandra ; Hoffmann, Markus ; Pöhlmann, Stefan ; McKay, Paul F. ; Shattock, Robin J. ; Wölfel, Roman ; Socher, Eileen ; Wagner, Ralf ; Eichler, Jutta ; Sticht, Heinrich ; Schuh, Wolfgang ; Neipel, Frank ; Ensser, Armin ; Mielenz, Dirk Alexander ; Tenbusch, Matthias ; Winkler, Thomas H. ; Grunwald, Thomas ; Überla, Klaus Thomas ; Jäck, Hans-Martin
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.
Gaßner, Tobias ; Trassinelli, Martino ; Heß, Regina ; Spillmann, Uwe ; Banaś, Dariusz ; Blumenhagen, Karl-Heinz ; Bosch, Fritz ; Brandau, Carsten ; Chen, Weidong ; Dimopoulou, Christina ; Förster, Eckhart ; Grisenti, Robert Evaristo ; Gumberidze, Alexandre ; Hagmann, Siegbert ; Hillenbrand, Pierre-Michel ; Indelicato, Paul ; Jagodziński, Paweł ; Kämpfer, Tino ; Kozhuharov, Christophor ; Lestinsky, Michael ; Liesen, Heinz-Dieter ; Litvinov, Yuri A. ; Loetzsch, Robert ; Manil, Bruno ; Märtin, Renate ; Nolden, Fritz ; Petridis, Nikolaos ; Sanjari, Mohammad Shahab ; Schulze, Kai-Sven ; Schwemlein, Max ; Simionovici, Alexandre S. ; Steck, Markus ; Stöhlker, Thomas ; Szabo, Csilla I. ; Trotsenko, Sergiy ; Uschmann, Ingo ; Weber, Günter ; Wehrhan, Ortrud ; Winckler, Nicolas ; Winters, Danyal Ferdinant Alexander ; Winters, Natalya ; Ziegler, Eric ; Beyer, Heinrich F.
Accurate spectroscopy of highly-charged high-Z ions in a storage ring is demonstrated to be feasible by the use of specially adapted crystal optics. The method has been applied for the measurement of the 1s Lamb shift in hydrogen-like gold (Au+78) in a storage ring through spectroscopy of the Lyman x-rays. This measurement represents the first result obtained for a high-Z element using high-resolution wavelength-dispersive spectroscopy in the hard x-ray regime, paving the way for sensitivity to higher- order QED effects.