Wang, Zijun and Schmidt, Fabian and Weisblum, Yiska and Muecksch, Frauke and Barnes, Christopher O. and Finkin, Shlomo and Schaefer-Babajew, Dennis and Cipolla, Melissa and Gaebler, Christian and Lieberman, Jenna A. and Oliveira, Thiago Y. and Yang, Zhi and Abernathy, Morgan E. and Huey-Tubman, Kathryn E. and Hurley, Arlene and Turroja, Martina and West, Kamille A. and Gordon, Kristie and Millard, Katrina G. and Ramos, Victor and Da Silva, Justin and Xu, Jianliang and Colbert, Robert A. and Patel, Roshni and Dizon, Juan and Unson-O'Brien, Cecille and Shimeliovich, Irina and Gazumyan, Anna and Caskey, Marina and Bjorkman, Pamela J. and Casellas, Rafael and Hatziioannou, Theodora and Bieniasz, Paul D. and Nussenzweig, Michel C. (2021) mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature, 592 (7855). pp. 616-622. ISSN 0028-0836. PMCID PMC7836122. doi:10.1038/s41586-021-03324-6. https://resolver.caltech.edu/CaltechAUTHORS:20210120-121820490
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Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20210120-121820490
Abstract
Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Eight weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S) and receptor binding domain (RBD) binding titers. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.
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| Additional Information: | © The Author(s), under exclusive licence to Springer Nature Limited 2021. Received 15 January 2021; Accepted 03 February 2021; Published 10 February 2021. We thank all study participants who devoted time to our research; Drs. Barry Coller and Sarah Schlesinger, the Rockefeller University Hospital Clinical Research Support Office and nursing staff; Charles M. Rice and all members of the M.C.N. laboratory for helpful discussions and Maša Jankovic for laboratory support; and Dr. Jost Vielmetter and the Protein Expression Center in the Beckman Institute at Caltech for expression assistance. Electron microscopy was performed in the Caltech Beckman Institute Resource Center for Transmission Electron Microscopy and we thank Drs. Songye Chen and Andrey Malyutin for technical assistance. This work was supported by NIH grant P01-AI138398-S1 (M.C.N. and P.J.B.) and 2U19AI111825 (M.C.N.); the Caltech Merkin Institute for Translational Research and P50 AI150464-13 (P.J.B.), a George Mason University Fast Grant (P.J.B.); R37-AI64003 to P.D.B.; R01AI78788 to T.H.; We thank Dr. Jost Vielmetter and the Protein Expression Center in the Beckman Institute at Caltech for expression assistance C.O.B. is supported by the HHMI Hanna Gray and Burroughs Wellcome PDEP fellowships. C.G. was supported by the Robert S. Wennett Post-Doctoral Fellowship, in part by the National Center for Advancing Translational Sciences (National Institutes of Health Clinical and Translational Science Award program, grant UL1 TR001866), and by the Shapiro-Silverberg Fund for the Advancement of Translational Research. P.D.B. and M.C.N. are Howard Hughes Medical Institute Investigators. Data availability statement: Data are provided in Extended Data Tables 1-7. The raw sequencing data and computer scripts associated with Fig. 2 have been deposited at Github (https://github.com/stratust/igpipeline). This study also uses data from “A Public Database of Memory and Naive B-Cell Receptor Sequences”, PDB (6VYB and 6NB6) and from “High frequency of shared clonotypes in human B cell receptor repertoires”. Cryo-EM maps associated with data reported in this manuscript will be deposited in the Electron Microscopy Data Bank (EMDB: https://www.ebi.ac.uk/pdbe/emdb/) under accession codes EMD-23393 (C601-S), EMD-23394 (C603-S), EMD-23395 (C643-S), EMD-23396 (C663-S), EMD-23397 (C666-S), EMD-23398 (C669-S), and EMD-23399 (C670-S). Code availability statement: Computer code to process the antibody sequences is available at GitHub (https://github.com/stratust/igpipeline). Author contributions: These authors contributed equally: Zijun Wang, Fabian Schmidt, Yiska Weisblum, Frauke Muecksch, Christopher O. Barnes, Shlomo Finkin, Dennis Schaefer-Babajew, Melissa Cipolla, Christian Gaebler, Jenna A. Lieberman. P.D.B., P.J.B., R.C., T.H., M.C.N., Z.W., F.S., Y.W., F.M., C.O.B, S.F., D.S.B., M.Cipolla. conceived, designed and analyzed the experiments. M.Caskey, C.G., J.A.L., K.W., D.S.B. designed clinical protocols Z.W., F.S., Y.W., F.M., C.O.B., S.F., D.S.B., M.Cipolla, J.D.S., A.G., Z.Y., M.E.A., K.E.H. carried out experiments. C.G., M.Caskey, K.W.D., R.A.C., A.H., K.G.M. recruited participants and executed clinical protocols. I.S., R.P, J.D., J.X. and C.U.O. processed clinical samples. T.Y.O. and V.R. performed bioinformatic analysis. R.C., P.D.B., P.J.B., T.H., and M.C.N. wrote the manuscript with input from all co-authors. Competing interests: The Rockefeller University has filed a provisional patent application in connection with this work on which Z.W. and M.C.N. are inventors (US patent 63/199, 676). Peer review information: Nature thanks the anonymous reviewers for their contribution to the peer review of this work. | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Group: | Richard N. Merkin Institute for Translational Research, COVID-19 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Subject Keywords: | Antibodies; Antimicrobial responses; SARS-CoV-2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Issue or Number: | 7855 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| PubMed Central ID: | PMC7836122 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1038/s41586-021-03324-6 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Record Number: | CaltechAUTHORS:20210120-121820490 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20210120-121820490 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Official Citation: | Wang, Z., Schmidt, F., Weisblum, Y. et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature 592, 616–622 (2021). https://doi.org/10.1038/s41586-021-03324-6 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||||||||||||||||||||||||||||||||||||||||
| ID Code: | 107591 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Collection: | CaltechAUTHORS | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Deposited By: | Tony Diaz | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Deposited On: | 20 Jan 2021 23:17 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Last Modified: | 23 Apr 2021 16:56 |
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