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The SARS-CoV-2 mRNA-1273 vaccine elicits more RBD-focused neutralization, but with broader antibody binding within the RBD

View ORCID ProfileAllison J. Greaney, View ORCID ProfileAndrea N. Loes, View ORCID ProfileLauren E. Gentles, View ORCID ProfileKatharine H.D. Crawford, View ORCID ProfileTyler N. Starr, Keara D. Malone, View ORCID ProfileHelen Y. Chu, View ORCID ProfileJesse D. Bloom
doi: https://doi.org/10.1101/2021.04.14.439844
Allison J. Greaney
1Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center; Seattle, WA 98109, USA
2Department of Genome Sciences & Medical Scientist Training Program, University of Washington; Seattle, WA 98195, USA
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  • ORCID record for Allison J. Greaney
Andrea N. Loes
1Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center; Seattle, WA 98109, USA
3Howard Hughes Medical Institute; Chevy Chase, MD 20815, USA
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Lauren E. Gentles
1Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center; Seattle, WA 98109, USA
4Department of Microbiology, University of Washington; Seattle, WA 98195, USA
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Katharine H.D. Crawford
1Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center; Seattle, WA 98109, USA
2Department of Genome Sciences & Medical Scientist Training Program, University of Washington; Seattle, WA 98195, USA
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Tyler N. Starr
1Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center; Seattle, WA 98109, USA
3Howard Hughes Medical Institute; Chevy Chase, MD 20815, USA
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Keara D. Malone
1Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center; Seattle, WA 98109, USA
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Helen Y. Chu
5Division of Allergy and Infectious Diseases, University of Washington; Seattle, Washington, USA
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  • ORCID record for Helen Y. Chu
Jesse D. Bloom
1Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center; Seattle, WA 98109, USA
3Howard Hughes Medical Institute; Chevy Chase, MD 20815, USA
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  • For correspondence: jbloom@fredhutch.org
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Abstract

The emergence of SARS-CoV-2 variants with mutations in key antibody epitopes has raised concerns that antigenic evolution will erode immunity. The susceptibility of immunity to viral evolution is shaped in part by the breadth of epitopes targeted. Here we compare the specificity of antibodies elicited by the mRNA-1273 vaccine versus natural infection. The neutralizing activity of vaccine-elicited antibodies is even more focused on the spike receptor-binding domain (RBD) than for infection-elicited antibodies. However, within the RBD, binding of vaccine-elicited antibodies is more broadly distributed across epitopes than for infection-elicited antibodies. This greater binding breadth means single RBD mutations have less impact on neutralization by vaccine sera than convalescent sera. Therefore, antibody immunity acquired by different means may have differing susceptibility to erosion by viral evolution.

One Sentence Summary Deep mutational scanning shows the mRNA-1273 RBD-binding antibody response is less affected by single viral mutations than the infection response.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵# Lead Contact jbloom{at}fredhutch.org

  • https://jbloomlab.github.io/SARS-CoV-2-RBD_MAP_Moderna/

  • https://github.com/jbloomlab/SARS-CoV-2-RBD_MAP_Moderna

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted April 14, 2021.
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The SARS-CoV-2 mRNA-1273 vaccine elicits more RBD-focused neutralization, but with broader antibody binding within the RBD
Allison J. Greaney, Andrea N. Loes, Lauren E. Gentles, Katharine H.D. Crawford, Tyler N. Starr, Keara D. Malone, Helen Y. Chu, Jesse D. Bloom
bioRxiv 2021.04.14.439844; doi: https://doi.org/10.1101/2021.04.14.439844
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The SARS-CoV-2 mRNA-1273 vaccine elicits more RBD-focused neutralization, but with broader antibody binding within the RBD
Allison J. Greaney, Andrea N. Loes, Lauren E. Gentles, Katharine H.D. Crawford, Tyler N. Starr, Keara D. Malone, Helen Y. Chu, Jesse D. Bloom
bioRxiv 2021.04.14.439844; doi: https://doi.org/10.1101/2021.04.14.439844

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