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A human coronavirus evolves antigenically to escape antibody immunity

Rachel Eguia, View ORCID ProfileKatharine H. D. Crawford, Terry Stevens-Ayers, View ORCID ProfileLaurel Kelnhofer-Millevolte, View ORCID ProfileAlexander L. Greninger, View ORCID ProfileJanet A. Englund, Michael J. Boeckh, View ORCID ProfileJesse D. Bloom
doi: https://doi.org/10.1101/2020.12.17.423313
Rachel Eguia
1Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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Katharine H. D. Crawford
1Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
2Department of Genome Sciences, University of Washington, Seattle, WA, USA
3Medical Scientist Training Program, University of Washington, Seattle, WA, USA
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Terry Stevens-Ayers
4Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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Laurel Kelnhofer-Millevolte
3Medical Scientist Training Program, University of Washington, Seattle, WA, USA
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  • ORCID record for Laurel Kelnhofer-Millevolte
Alexander L. Greninger
4Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
5Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
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Janet A. Englund
6Seattle Children’s Research Institute, Seattle, WA USA
7Department of Pediatrics, University of Washington, Seattle, WA USA
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Michael J. Boeckh
4Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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Jesse D. Bloom
1Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
2Department of Genome Sciences, University of Washington, Seattle, WA, USA
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  • For correspondence: jbloom@fredhutch.org
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Abstract

There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.

Competing Interest Statement

MJB has consulted for Moderna and Vir Biotechnologies, and received research funding from Regeneron and Vir Biotechnologies. JAE has consulted for Meissa Vaccines and Sanofi Pasteur, and received research funding from Merck, GlaxoSmithKline, Pfizer, and AstraZeneca. The other authors declare no competing interests.

Footnotes

  • https://github.com/jbloomlab/CoV_229E_antigenic_drift

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 December 18, 2020.
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A human coronavirus evolves antigenically to escape antibody immunity
Rachel Eguia, Katharine H. D. Crawford, Terry Stevens-Ayers, Laurel Kelnhofer-Millevolte, Alexander L. Greninger, Janet A. Englund, Michael J. Boeckh, Jesse D. Bloom
bioRxiv 2020.12.17.423313; doi: https://doi.org/10.1101/2020.12.17.423313
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A human coronavirus evolves antigenically to escape antibody immunity
Rachel Eguia, Katharine H. D. Crawford, Terry Stevens-Ayers, Laurel Kelnhofer-Millevolte, Alexander L. Greninger, Janet A. Englund, Michael J. Boeckh, Jesse D. Bloom
bioRxiv 2020.12.17.423313; doi: https://doi.org/10.1101/2020.12.17.423313

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