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Mapping SARS-CoV-2 antigenic relationships and serological responses

Samuel H. Wilks, Barbara Mühlemann, Xiaoying Shen, Sina Türeli, Eric B. LeGresley, Antonia Netzl, Miguela A. Caniza, Jesus N. Chacaltana-Huarcaya, Xiaoju Daniell, Michael B. Datto, Thomas N. Denny, Christian Drosten, Ron A. M. Fouchier, Patricia J. Garcia, Peter J. Halfmann, Agatha Jassem, Terry C. Jones, Yoshihiro Kawaoka, Florian Krammer, Charlene McDanal, Rolando Pajon, Viviana Simon, Melissa Stockwell, Haili Tang, Harm van Bakel, Richard Webby, David C. Montefiori, Derek J. Smith
doi: https://doi.org/10.1101/2022.01.28.477987
Samuel H. Wilks
1Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK
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Barbara Mühlemann
2Institute of Virology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
3German Centre for Infection Research (DZIF), partner site Charité, 10117 Berlin, Germany
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Xiaoying Shen
4Department of Surgery, Duke University School of Medicine, Durham, NC, USA
5Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Sina Türeli
1Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK
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Eric B. LeGresley
1Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK
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Antonia Netzl
1Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK
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Miguela A. Caniza
6Department of Global Pediatric Medicine, Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA
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Jesus N. Chacaltana-Huarcaya
7Hospital Nacional Daniel A Carrión, Callao, Bellavista, Peru
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Xiaoju Daniell
4Department of Surgery, Duke University School of Medicine, Durham, NC, USA
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Michael B. Datto
8Department of Pathology, Duke University School of Medicine, Durham, NC, USA
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Thomas N. Denny
5Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Christian Drosten
2Institute of Virology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
3German Centre for Infection Research (DZIF), partner site Charité, 10117 Berlin, Germany
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Ron A. M. Fouchier
9Erasmus Medical Center, Rotterdam, Netherlands
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Patricia J. Garcia
10School of Public Health, Universidad Peruana Cayetano Heredia, Lima, Peru
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Peter J. Halfmann
11Department of Pathobiological Science, School of Veterinary Medicine University of Wisconsin-Madison, Madison, WI, USA
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Agatha Jassem
12BC Centre for Disease Control, Vancouver, British Columbia, Canada
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Terry C. Jones
1Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK
2Institute of Virology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
3German Centre for Infection Research (DZIF), partner site Charité, 10117 Berlin, Germany
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Yoshihiro Kawaoka
11Department of Pathobiological Science, School of Veterinary Medicine University of Wisconsin-Madison, Madison, WI, USA
13Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
14The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan
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Florian Krammer
15Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
16Department of Pathology, Cellular and Molecular Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Charlene McDanal
4Department of Surgery, Duke University School of Medicine, Durham, NC, USA
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Rolando Pajon
17Moderna, Inc., Cambridge, MA, USA
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Viviana Simon
15Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
16Department of Pathology, Cellular and Molecular Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
18Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
19The Global Health and Emerging Pathogen Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Melissa Stockwell
20Division of Child and Adolescent Health, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, and Department of Population and Family Health, Mailman School of Public Health, New York, NY, USA
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Haili Tang
4Department of Surgery, Duke University School of Medicine, Durham, NC, USA
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Harm van Bakel
21Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Richard Webby
22Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA
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David C. Montefiori
4Department of Surgery, Duke University School of Medicine, Durham, NC, USA
5Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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  • For correspondence: dsmith@zoo.cam.ac.uk
Derek J. Smith
1Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK
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  • For correspondence: dsmith@zoo.cam.ac.uk
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Abstract

During the SARS-CoV-2 pandemic, multiple variants with differing amounts of escape from pre-existing immunity have emerged, causing concerns about continued protection. Here, we use antigenic cartography to quantify and visualize the antigenic relationships among 16 SARS-CoV-2 variants titrated against serum samples taken post-vaccination and post-infection with seven different variants. We find major antigenic differences caused by substitutions at positions 417, 452, 484, and possibly 501. B.1.1.529 (Omicron) showed the highest escape from all sera tested. Visualization of serological responses as antibody landscapes shows how reactivity clusters in different regions of antigenic space. We find changes in immunodominance of different spike regions depending on the variant an individual was exposed to, with implications for variant risk assessment and vaccine strain selection.

One sentence summary Antigenic Cartography of SARS-CoV-2 variants reveals amino acid substitutions governing immune escape and immunodominance patterns.

Competing Interest Statement

The authors have declared no competing interest.

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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-NC-ND 4.0 International license.
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Posted January 28, 2022.
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Mapping SARS-CoV-2 antigenic relationships and serological responses
Samuel H. Wilks, Barbara Mühlemann, Xiaoying Shen, Sina Türeli, Eric B. LeGresley, Antonia Netzl, Miguela A. Caniza, Jesus N. Chacaltana-Huarcaya, Xiaoju Daniell, Michael B. Datto, Thomas N. Denny, Christian Drosten, Ron A. M. Fouchier, Patricia J. Garcia, Peter J. Halfmann, Agatha Jassem, Terry C. Jones, Yoshihiro Kawaoka, Florian Krammer, Charlene McDanal, Rolando Pajon, Viviana Simon, Melissa Stockwell, Haili Tang, Harm van Bakel, Richard Webby, David C. Montefiori, Derek J. Smith
bioRxiv 2022.01.28.477987; doi: https://doi.org/10.1101/2022.01.28.477987
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Mapping SARS-CoV-2 antigenic relationships and serological responses
Samuel H. Wilks, Barbara Mühlemann, Xiaoying Shen, Sina Türeli, Eric B. LeGresley, Antonia Netzl, Miguela A. Caniza, Jesus N. Chacaltana-Huarcaya, Xiaoju Daniell, Michael B. Datto, Thomas N. Denny, Christian Drosten, Ron A. M. Fouchier, Patricia J. Garcia, Peter J. Halfmann, Agatha Jassem, Terry C. Jones, Yoshihiro Kawaoka, Florian Krammer, Charlene McDanal, Rolando Pajon, Viviana Simon, Melissa Stockwell, Haili Tang, Harm van Bakel, Richard Webby, David C. Montefiori, Derek J. Smith
bioRxiv 2022.01.28.477987; doi: https://doi.org/10.1101/2022.01.28.477987

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