SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies

We thank all study participants who devoted samples and time to our research, Dr. Kim Stahlberg and Meilan Zuo for patient recruitment, Stefanie Bandura, Matthias Sillmann, Doreen Brandl, Patricia Tscheak, and Sabine Engl for excellent technical assistance, and Dr. Marcel A. Müller and Dr. Daniela Niemeyer for support with BSL3 work. We acknowledge BIAFFIN GmbH & Co. KG (Kassel, Germany) for performance of SPR measurements and the Flow and Mass Cytometry Core Facility at Charité-Universitätsmedizin Berlin for support with single-cell sorting. We thank Robyn Stanfield for assistance in data collection, Fangzhu Zhao for assistance in the biolayer interferometry binding assay, and the staff of Advanced Light Source beamline 5.0.1 and Stanford Synchrotron Radiation Laboratory (SSRL) beamline 12-1 for assistance. SARS-CoV-2 RBD variants antigens for sera testing were kindly provided by InVivo BioTech Services GmbH (Hennigsdorf, Germany) to the Seramun Diagnostica GmbH (Heidesee, Germany). S.M.R. and J.K. are participants in the BIH-Charité Junior Clinician Scientist Program and V.M.C is supported by Berlin Institute of Health (BIH) Charité Clinician Scientist program both funded by Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. Funding: This work was supported by the Bill and Melinda Gates Foundation INV-004923 (I.A.W.), by the Bavarian State Ministry of Science and the Arts; University Hospital; Ludwig-Maximilians-Universität Munich; German Ministry for Education and Research (Proj. Nr.: 01KI20271, M.H.; Connect-Generate 01GM1908D, H.P.); by the Helmholtz Association (ExNet-0009-Phase2-3, D.S.; HIL-A03, H.P.), by the German Research Foundation (DFG) (PR1274/3-1 and PR1274/5-1, H.P.), and by the Austrian Science Fund (FWF J4157-B30, M.R.). Parts of the work was funded by the European Union's Horizon 2020 research and innovation program through project RECOVER (GA101003589) to C.D.; the German Ministry of Research through the projects VARIPath (01KI2021) to V.M.C and NaFoUniMedCovid19 - COVIM, FKZ: 01KX2021 to C.D., and V.M.C. This research used resources of the Advanced Light Source, which is a DOE Office of Science User Facility under contract number DE-AC02-05CH11231.Use of the SSRL, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02–76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). Author contributions: Conceptualization: S.M.R., M.Y., H.-C.K., V.M.C., H.P., I.A.W., and J.K.; Patient recruitment and sample preparation: S.M.R., M.R., M.A.H., I.K., T.M.E., C.G., A.W., M.H., H.G., G.W., S.H., H.P., and J.K.; Antibody production: S.M.R., S.v.H., E.S.-S., M.R., S.E.B., H.F.R., M.A.H., L.S., D.K., N.v.W., and J.K.; Antibody reactivity testing: H.-C.K.; Serological assays and neutralization testing: V.M.C., M.L.S., T.S., L.M.J., and C.D.; Protein production and crystallography: M.Y., W.Y., Y.H., and H.T.; Software: M.B., J.H., and S.M.R.; Resources: V.M.C., M.H., G.W., D.S., C.D., H.P., and I.A.W.; Writing – Original Draft: S.M.R., M.Y., H.-C.K., H.P., I.A.W., and J.K.; Writing – Review and Editing: all authors; Supervision: S.M.R., M.Y., H.-C.K., V.M.C., H.P., I.A.W., and J.K. Competing interests: The German Center for Neurodegenerative Diseases (DZNE) and Charité-Universitätsmedizin Berlin have filed a patent application on antibodies for the treatment of SARS-CoV-2 infection described in an earlier publication, on which S.M.R., H.-C.K., V.M.C., E.S.-S., H.P., and J.K. are named as inventors. V.M.C. is named together with Euroimmun GmbH on a patent application filed recently regarding the diagnostic of SARS-CoV-2 by antibody testing. Data and materials availability: X-ray coordinates and structure factors are deposited at the RCSB Protein Data Bank under accession codes 7S5P, 7S5Q and 7S5R. The amino acid sequences of the antibodies described in this study can be found in table S3. All requests for materials including antibodies, viruses, plasmids and proteins generated in this study should be directed to the corresponding authors. Materials will be made available for non-commercial usage. This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.

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