TY - JOUR
T1 - Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients
AU - Kreer, Christoph
AU - Zehner, Matthias
AU - Weber, Timm
AU - Ercanoglu, Meryem S.
AU - Gieselmann, Lutz
AU - Rohde, Cornelius
AU - Halwe, Sandro
AU - Korenkov, Michael
AU - Schommers, Philipp
AU - Vanshylla, Kanika
AU - Di Cristanziano, Veronica
AU - Janicki, Hanna
AU - Brinker, Reinhild
AU - Ashurov, Artem
AU - Kraehling, Verena
AU - Kupke, Alexandra
AU - Cohen-Dvashi, Hadas
AU - Koch, Manuel
AU - Eckert, Jan Mathis
AU - Lederer, Simone
AU - Pfeifer, Nico
AU - Wolf, Timo
AU - Vehreschild, Maria J. G. T.
AU - Wendtner, Clemens
AU - Diskin, Ron
AU - Gruell, Henning
AU - Becker, Stephan
AU - Klein, Florian
N1 - We thank all study participants who devoted time to our research; members of the Klein and Becker Laboratories for continuous support and helpful discussions; Jason McLellan, Nianshuang Wang, and Daniel Wrapp for sharing the SARS-CoV-2 S ectodomain plasmid; Florian Krammer for sharing the RBD plasmid; Simon Pöpsel and Robert Hänsel-Hertsch for helpful discussions and technical support; Daniela Weiland and Nadine Henn for lab management and assistance; Birgit Gathof and Sabine Adam of the Institute of Transfusion Medicine of the University Hospital of Cologne for providing blood samples for NGS analysis; as well as Heidrun Schößler and Ralf Ortmanns of the health department of Heinsberg for support with patient recruitment. This work was funded by grants from the German Center for Infection Research (DZIF) to F.K. and S.B., the German Research Foundation (DFG) (CRC 1279 and CRC 1310 to F.K., FOR2722 to M.K.; EXC 2064/1, project no. 390727645 to N.P.), the European Research Council (ERC-StG639961 to F.K.), the German Federal Ministry of Education and Research (BMBF) within the Medical Informatics Initiative (DIFUTURE) (reference 01ZZ1804D to S.L. and N.P.), the Ben B. and Joyce E. Eisenberg Foundation to R.D., the Ernst I. Ascher Foundation and Natan Sharansky to R.D. Author contributions - Conceptualization, F.K.; Methodology, F.K., S.B., C.K., M.Z., M.S.E., L.G., C.R., S.H., S.L., and N.P.; Investigation, C.K., M.Z., T. Weber, L.G., M.S.E., C.R., S.H., M. Korenkov, H.G., P.S., K.V., V.D.C., H.J., R.B., A.A., V.K., A.K., H.C.-D., M. Koch, J.M.E., T. Wolf, M.J.G.T.V., and C.W.; Software, C.K., S.L., and N.P.; Formal Analysis, C.K., M.Z., S.L., N.P., and F.K.; Resources, F.K., S.B., and R.D.; Writing – Original Draft, F.K., C.K., M.Z., T. Weber, and H.G.; Writing – Review and Editing, all authors; Supervision, F.K., S.B., and R.D.
PY - 2020/8/20
Y1 - 2020/8/20
N2 - The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and the world economy. Because approved drugs and vaccines are limited or not available, new options for COVID-19 treatment and prevention are in high demand. To identify SARS-CoV-2-neutralizing antibodies, we analyzed the antibody response of 12 COVID-19 patients from 8 to 69 days after diagnosis. By screening 4,313 SARS-CoV-2-reactive B cells, we isolated 255 antibodies from different time points as early as 8 days after diagnosis. Of these, 28 potently neutralized authentic SARS-CoV-2 with IC 100 as low as 0.04 μg/mL, showing a broad spectrum of variable (V) genes and low levels of somatic mutations. Interestingly, potential precursor sequences were identified in naive B cell repertoires from 48 healthy individuals who were sampled before the COVID-19 pandemic. Our results demonstrate that SARS-CoV-2-neutralizing antibodies are readily generated from a diverse pool of precursors, fostering hope for rapid induction of a protective immune response upon vaccination.Errata: We discovered that values for 2 out of 79 antibodies have unfortunately been wrongly reported. For antibody FnC1t1p2_A5, the IC100 is 50 μg/mL instead of 16 μg/mL; for antibody CnC2t1p1_B10, the IC100 is >100 μg/mL instead of 12.5 μg/mL. For the latter antibody, binding characteristics were also corrected. As a consequence, the total number of neutralizing antibodies reported is 27 instead of 28. Changes affect Figures 3, 4, S3, S4, and S5, Tables S3 and S4, and text on pages 1, 3, 5, and 7. Importantly, the corrections have no impact on the conclusions in this paper. We apologize for any inconvenience that may have been caused by this error.
AB - The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and the world economy. Because approved drugs and vaccines are limited or not available, new options for COVID-19 treatment and prevention are in high demand. To identify SARS-CoV-2-neutralizing antibodies, we analyzed the antibody response of 12 COVID-19 patients from 8 to 69 days after diagnosis. By screening 4,313 SARS-CoV-2-reactive B cells, we isolated 255 antibodies from different time points as early as 8 days after diagnosis. Of these, 28 potently neutralized authentic SARS-CoV-2 with IC 100 as low as 0.04 μg/mL, showing a broad spectrum of variable (V) genes and low levels of somatic mutations. Interestingly, potential precursor sequences were identified in naive B cell repertoires from 48 healthy individuals who were sampled before the COVID-19 pandemic. Our results demonstrate that SARS-CoV-2-neutralizing antibodies are readily generated from a diverse pool of precursors, fostering hope for rapid induction of a protective immune response upon vaccination.Errata: We discovered that values for 2 out of 79 antibodies have unfortunately been wrongly reported. For antibody FnC1t1p2_A5, the IC100 is 50 μg/mL instead of 16 μg/mL; for antibody CnC2t1p1_B10, the IC100 is >100 μg/mL instead of 12.5 μg/mL. For the latter antibody, binding characteristics were also corrected. As a consequence, the total number of neutralizing antibodies reported is 27 instead of 28. Changes affect Figures 3, 4, S3, S4, and S5, Tables S3 and S4, and text on pages 1, 3, 5, and 7. Importantly, the corrections have no impact on the conclusions in this paper. We apologize for any inconvenience that may have been caused by this error.
UR - https://www.scopus.com/pages/publications/85087953925
U2 - 10.1016/j.cell.2020.06.044
DO - 10.1016/j.cell.2020.06.044
M3 - Article
SN - 0092-8674
VL - 182
SP - 843
EP - 854
JO - Cell
JF - Cell
IS - 4
ER -