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Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Young-Jun Park, Dora Pinto, Alexandra C. Walls, Zhuoming Liu, Anna De Marco, Fabio Benigni, Fabrizia Zatta, Chiara Silacci-Fregni, Jessica Bassi, Kaitlin R. Sprouse, Amin Addetia, John E. Bowen, Cameron Stewart, Martina Giurdanella, Christian Saliba, Barbara Guarino, Michael A. Schmid, Nicholas Franko, Jennifer Logue, Ha V. Dang, Kevin Hauser, Julia di Iulio, William Rivera, Gretja Schnell, Florian A. Lempp, Javier Janer, Rana Abdelnabi, Piet Maes, Paolo Ferrari, Alessandro Ceschi, Olivier Giannini, Guilherme Dias de Melo, Lauriane Kergoat, Hervé Bourhy, Johan Neyts, Leah Soriaga, Lisa A. Purcell, Gyorgy Snell, Sean P.J. Whelan, Antonio Lanzavecchia, Herbert W. Virgin, Luca Piccoli, Helen Chu, Matteo Samuele Pizzuto, Davide Corti, David Veesler
doi: https://doi.org/10.1101/2022.05.08.491108
Young-Jun Park
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
2Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA
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Dora Pinto
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Alexandra C. Walls
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
2Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA
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Zhuoming Liu
4Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
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Anna De Marco
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Fabio Benigni
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Fabrizia Zatta
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Chiara Silacci-Fregni
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Jessica Bassi
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Kaitlin R. Sprouse
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
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Amin Addetia
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
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John E. Bowen
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
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Cameron Stewart
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
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Martina Giurdanella
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Christian Saliba
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Barbara Guarino
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Michael A. Schmid
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Nicholas Franko
5Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195, USA
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Jennifer Logue
5Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195, USA
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Ha V. Dang
6Vir Biotechnology, San Francisco, CA 94158, USA
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Kevin Hauser
6Vir Biotechnology, San Francisco, CA 94158, USA
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Julia di Iulio
6Vir Biotechnology, San Francisco, CA 94158, USA
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William Rivera
6Vir Biotechnology, San Francisco, CA 94158, USA
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Gretja Schnell
6Vir Biotechnology, San Francisco, CA 94158, USA
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Florian A. Lempp
6Vir Biotechnology, San Francisco, CA 94158, USA
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Javier Janer
4Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
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Rana Abdelnabi
7Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium
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Piet Maes
7Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium
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Paolo Ferrari
9Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland
10Division of Nephrology, Ente Ospedaliero Cantonale, Lugano, Switzerland
11Clinical School, University of New South Wales, Sydney, New South Wales, Australia
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Alessandro Ceschi
9Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland
12Clinical Trial Unit, Ente Ospedaliero Cantonale, Lugano, Switzerland
13Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland
14Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland
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Olivier Giannini
9Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland
15Department of Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
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Guilherme Dias de Melo
16Institut Pasteur, Université de Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, Paris, F-75015, France
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Lauriane Kergoat
16Institut Pasteur, Université de Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, Paris, F-75015, France
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Hervé Bourhy
16Institut Pasteur, Université de Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, Paris, F-75015, France
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Johan Neyts
7Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium
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Leah Soriaga
6Vir Biotechnology, San Francisco, CA 94158, USA
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Lisa A. Purcell
6Vir Biotechnology, San Francisco, CA 94158, USA
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Gyorgy Snell
6Vir Biotechnology, San Francisco, CA 94158, USA
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Sean P.J. Whelan
4Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
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Antonio Lanzavecchia
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Herbert W. Virgin
6Vir Biotechnology, San Francisco, CA 94158, USA
17Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA
18Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
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Luca Piccoli
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Helen Chu
5Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195, USA
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Matteo Samuele Pizzuto
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Davide Corti
3Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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  • For correspondence: dveesler@uw.edu dcorti@vir.bio
David Veesler
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
2Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA
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  • For correspondence: dveesler@uw.edu dcorti@vir.bio
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Abstract

SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development.

Competing Interest Statement

D.P., Ad.M., F.Z., M.G., C.S.F., J.B., C.S., H.V.D., K.H., W.R., M.A.S., G.Sc., B.G., F.B., J.d.I., F.A.L., G.S., L.P., A.T., H.W.V., A.L., M.S.P. and D.C. are employees of Vir Biotechnology Inc. and may hold shares in Vir Biotechnology Inc. L.A.P. is a former employee and shareholder in Regeneron Pharmaceuticals. Regeneron provided no funding for this work. H.W.V. is a founder and holds shares in PierianDx and Casma Therapeutics. Neither company provided resources. D.C. is currently listed as an inventor on multiple patent applications, which disclose the subject matter described in this manuscript. The Veesler laboratory has received a sponsored research agreement from Vir Biotechnology Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Footnotes

  • ↵* These authors contributed equally

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-NC-ND 4.0 International license.
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Imprinted antibody responses against SARS-CoV-2 Omicron sublineages
Young-Jun Park, Dora Pinto, Alexandra C. Walls, Zhuoming Liu, Anna De Marco, Fabio Benigni, Fabrizia Zatta, Chiara Silacci-Fregni, Jessica Bassi, Kaitlin R. Sprouse, Amin Addetia, John E. Bowen, Cameron Stewart, Martina Giurdanella, Christian Saliba, Barbara Guarino, Michael A. Schmid, Nicholas Franko, Jennifer Logue, Ha V. Dang, Kevin Hauser, Julia di Iulio, William Rivera, Gretja Schnell, Florian A. Lempp, Javier Janer, Rana Abdelnabi, Piet Maes, Paolo Ferrari, Alessandro Ceschi, Olivier Giannini, Guilherme Dias de Melo, Lauriane Kergoat, Hervé Bourhy, Johan Neyts, Leah Soriaga, Lisa A. Purcell, Gyorgy Snell, Sean P.J. Whelan, Antonio Lanzavecchia, Herbert W. Virgin, Luca Piccoli, Helen Chu, Matteo Samuele Pizzuto, Davide Corti, David Veesler
bioRxiv 2022.05.08.491108; doi: https://doi.org/10.1101/2022.05.08.491108
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Imprinted antibody responses against SARS-CoV-2 Omicron sublineages
Young-Jun Park, Dora Pinto, Alexandra C. Walls, Zhuoming Liu, Anna De Marco, Fabio Benigni, Fabrizia Zatta, Chiara Silacci-Fregni, Jessica Bassi, Kaitlin R. Sprouse, Amin Addetia, John E. Bowen, Cameron Stewart, Martina Giurdanella, Christian Saliba, Barbara Guarino, Michael A. Schmid, Nicholas Franko, Jennifer Logue, Ha V. Dang, Kevin Hauser, Julia di Iulio, William Rivera, Gretja Schnell, Florian A. Lempp, Javier Janer, Rana Abdelnabi, Piet Maes, Paolo Ferrari, Alessandro Ceschi, Olivier Giannini, Guilherme Dias de Melo, Lauriane Kergoat, Hervé Bourhy, Johan Neyts, Leah Soriaga, Lisa A. Purcell, Gyorgy Snell, Sean P.J. Whelan, Antonio Lanzavecchia, Herbert W. Virgin, Luca Piccoli, Helen Chu, Matteo Samuele Pizzuto, Davide Corti, David Veesler
bioRxiv 2022.05.08.491108; doi: https://doi.org/10.1101/2022.05.08.491108

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