Wang, Zijun and Muecksch, Frauke and Schaefer-Babajew, Dennis and Finkin, Shlomo and Viant, Charlotte and Gaebler, Christian and Hoffmann, Hans-Heinrich and Barnes, Christopher O. and Cipolla, Melissa and Ramos, Victor and Oliveira, Thiago Y. and Cho, Alice and Schmidt, Fabian and da Silva, Justin and Bednarski, Eva and Aguado, Lauren and Yee, Jim and Daga, Mridushi and Turroja, Martina and Millard, Katrina G. and Jankovic, Mila and Gazumyan, Anna and Zhao, Zhen and Rice, Charles M. and Bieniasz, Paul D. and Caskey, Marina and Hatziioannou, Theodora and Nussenzweig, Michel C. (2021) Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection. Nature, 595 (7867). pp. 426-431. ISSN 0028-0836. PMCID PMC8277577. doi:10.1038/s41586-021-03696-9. https://resolver.caltech.edu/CaltechAUTHORS:20210510-104403619
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Abstract
More than one year after its inception, the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains difficult to control despite the availability of several working vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies. Here we report on a cohort of 63 individuals who have recovered from COVID-19 assessed at 1.3, 6.2 and 12 months after SARS-CoV-2 infection, 41% of whom also received mRNA vaccines. In the absence of vaccination, antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable between 6 and 12 months after infection. Vaccination increases all components of the humoral response and, as expected, results in serum neutralizing activities against variants of concern similar to or greater than the neutralizing activity against the original Wuhan Hu-1 strain achieved by vaccination of naive individuals. The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in the variants of concern. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand markedly after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants.
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| Alternate Title: | Vaccination boosts naturally enhanced neutralizing breadth to SARS-CoV-2 one year after infection | ||||||||||||||||||||||||||||||||||||||||||||||
| Additional Information: | © 2021 Nature Publishing Group. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 02 May 2021; Accepted 04 June 2021; Published 14 June 2021. We thank all study participants who devoted time to our research; The Rockefeller University Hospital nursing staff and Clinical Research Support Office and nursing staff; M. O. Frank, M. Bergh and R. B. Darnell for SARS-CoV-2 saliva PCR testing; P. J. Bjorkman and all members of the M.C.N. laboratory for helpful discussions and M. Jankovic for laboratory support. This work was supported by NIH grant P01-AI138398-S1 (M.C.N., C.M.R. and P.J.B.) and 2U19AI111825 (M.C.N. and C.M.R); George Mason University Fast Grants to C.M.R., 3 R01-AI091707-10S1 to C.M.R.; The G. Harold and Leila Y. Mathers Charitable Foundation to C.M.R.; NIH grant R37-AI64003 to P.D.B.; NIH grant R01AI78788 to T.H. We thank J. 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. F.M. is supported by the Bulgari Women & Science Fellowship in COVID-19 Research. Data availability: Data are provided in Supplementary Tables 1–8. The raw sequencing data have been deposited at Github (https://github.com/stratust/igpipeline). This study also uses data from https://doi.org/10.5061/dryad.35ks2 and from https://doi.org/10.1038/s41586-019-0934-8. Code availability: Computer code to process the antibody sequences and/or associated with Fig. 2 and Extended Data Fig. 5 is available at GitHub (https://github.com/stratust/igpipeline). These authors contributed equally: Zijun Wang, Frauke Muecksch, Dennis Schaefer-Babajew, Shlomo Finkin, Charlotte Viant, Christian Gaebler Author Contributions: P.D.B., T.H., C.M.R. and M.C.N. conceived, designed and analysed the experiments. M. Caskey and C.G. designed clinical protocols. Z.W., F.M., D.S.-B., S.F., C.V., H.-H.H., C.O.B., A.C., F.S., J.D.S., E.B., L.A., J.Y., M.J. and Z.Z. carried out experiments. A.G. and M. Cipolla produced antibodies. D.S.-B., M.D., M.T., K.G.M., C.G. and M. Caskey recruited participants, executed clinical protocols and processed samples. T.Y.O. and V.R. performed bioinformatic analysis. Z.W., F.M., D.S.-B., C.G. 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 M.C.N. is an inventor (US patent 63/021,387). The patent has been licensed by Rockefeller University to Bristol Meyers Squib. Z.Z. received seed instruments and sponsored research funding from ET Healthcare. Peer review information: Nature thanks Thushan de Silva, Pei-Yong Shi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. | ||||||||||||||||||||||||||||||||||||||||||||||
| Group: | COVID-19 | ||||||||||||||||||||||||||||||||||||||||||||||
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| Subject Keywords: | Antibodies; Antimicrobial responses; SARS-CoV-2 | ||||||||||||||||||||||||||||||||||||||||||||||
| Issue or Number: | 7867 | ||||||||||||||||||||||||||||||||||||||||||||||
| PubMed Central ID: | PMC8277577 | ||||||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1038/s41586-021-03696-9 | ||||||||||||||||||||||||||||||||||||||||||||||
| Record Number: | CaltechAUTHORS:20210510-104403619 | ||||||||||||||||||||||||||||||||||||||||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20210510-104403619 | ||||||||||||||||||||||||||||||||||||||||||||||
| Official Citation: | Wang, Z., Muecksch, F., Schaefer-Babajew, D. et al. Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection. Nature 595, 426–431 (2021). https://doi.org/10.1038/s41586-021-03696-9 | ||||||||||||||||||||||||||||||||||||||||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||||||||||||||||||||||||||||||||||||
| ID Code: | 109032 | ||||||||||||||||||||||||||||||||||||||||||||||
| Collection: | CaltechAUTHORS | ||||||||||||||||||||||||||||||||||||||||||||||
| Deposited By: | Tony Diaz | ||||||||||||||||||||||||||||||||||||||||||||||
| Deposited On: | 10 May 2021 17:54 | ||||||||||||||||||||||||||||||||||||||||||||||
| Last Modified: | 26 Aug 2021 18:52 |
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