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A live attenuated vaccine confers superior mucosal and systemic immunity to SARS-CoV-2 variants

View ORCID ProfileGeraldine Nouailles, View ORCID ProfileJulia M. Adler, Peter Pennitz, View ORCID ProfileStefan Peidli, Gustavo Teixeira Alves, Morris Baumgart, Judith Bushe, Anne Voss, Alina Langenhagen, View ORCID ProfileFabian Pott, View ORCID ProfileJulia Kazmierski, Cengiz Goekeri, Szandor Simmons, Na Xing, Christine Langner, Ricardo Martin Vidal, Azza Abdelgawad, Susanne Herwig, Günter Cichon, Daniela Niemeyer, View ORCID ProfileChristian Drosten, View ORCID ProfileChristine Goffinet, View ORCID ProfileMarkus Landthaler, Nils Blüthgen, Haibo Wu, View ORCID ProfileMartin Witzenrath, View ORCID ProfileAchim D. Gruber, Samantha D. Praktiknjo, View ORCID ProfileNikolaus Osterrieder, View ORCID ProfileEmanuel Wyler, Dusan Kunec, View ORCID ProfileJakob Trimpert
doi: https://doi.org/10.1101/2022.05.16.492138
Geraldine Nouailles
1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany
2Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany
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Julia M. Adler
1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany
3Freie Universität Berlin, Institut für Virologie, Berlin, Germany
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Peter Pennitz
1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany
2Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany
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Stefan Peidli
4Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Berlin, Germany; IRI Life Sciences, Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany
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Gustavo Teixeira Alves
5Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology (BIMSB), Berlin, Germany
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Morris Baumgart
1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany
2Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany
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Judith Bushe
6Freie Universität Berlin, Institut für Tierpathologie, Berlin, Germany
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Anne Voss
6Freie Universität Berlin, Institut für Tierpathologie, Berlin, Germany
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Alina Langenhagen
6Freie Universität Berlin, Institut für Tierpathologie, Berlin, Germany
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Fabian Pott
7Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany
8Berlin Institute of Health (BIH), Berlin, Germany
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Julia Kazmierski
7Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany
8Berlin Institute of Health (BIH), Berlin, Germany
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Cengiz Goekeri
1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany
9Cyprus International University, Faculty of Medicine, Nicosia, Cyprus
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Szandor Simmons
10Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Physiology, Berlin, Germany
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Na Xing
3Freie Universität Berlin, Institut für Virologie, Berlin, Germany
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Christine Langner
3Freie Universität Berlin, Institut für Virologie, Berlin, Germany
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Ricardo Martin Vidal
3Freie Universität Berlin, Institut für Virologie, Berlin, Germany
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Azza Abdelgawad
3Freie Universität Berlin, Institut für Virologie, Berlin, Germany
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Susanne Herwig
11Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gynecology, Berlin, Germany
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Günter Cichon
11Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gynecology, Berlin, Germany
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Daniela Niemeyer
7Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany
12German Center for Infection Research (DZIF), partner site Charité, Berlin, Germany
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Christian Drosten
7Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany
12German Center for Infection Research (DZIF), partner site Charité, Berlin, Germany
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Christine Goffinet
7Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany
8Berlin Institute of Health (BIH), Berlin, Germany
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Markus Landthaler
13Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; IRI Life Sciences, Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany
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Nils Blüthgen
4Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Berlin, Germany; IRI Life Sciences, Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany
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Haibo Wu
14School of Life Sciences, Chongqing University, Chongqing 401331, China
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Martin Witzenrath
1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Pulmonary Inflammation, Berlin, Germany
2Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany
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Achim D. Gruber
6Freie Universität Berlin, Institut für Tierpathologie, Berlin, Germany
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Samantha D. Praktiknjo
4Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Berlin, Germany; IRI Life Sciences, Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany
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Nikolaus Osterrieder
3Freie Universität Berlin, Institut für Virologie, Berlin, Germany
15Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong
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Emanuel Wyler
5Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology (BIMSB), Berlin, Germany
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Dusan Kunec
3Freie Universität Berlin, Institut für Virologie, Berlin, Germany
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Jakob Trimpert
3Freie Universität Berlin, Institut für Virologie, Berlin, Germany
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  • For correspondence: trimpert.jakob@fu-berlin.de
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Abstract

Vaccines are a cornerstone in COVID-19 pandemic management. Here, we compare immune responses to and preclinical efficacy of the mRNA vaccine BNT162b2, an adenovirus-vectored spike vaccine, and the live-attenuated-virus vaccine candidate sCPD9 after single and double vaccination in Syrian hamsters. All regimens containing sCPD9 showed superior efficacy. The robust immunity elicited by sCPD9 was evident in a wide range of immune parameters after challenge with heterologous SARS-CoV-2 including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue. Our results demonstrate that use of live-attenuated vaccines may offer advantages over available COVID-19 vaccines, specifically when applied as booster, and may provide a solution for containment of the COVID-19 pandemic.

Competing Interest Statement

Related to this work, Freie Universität Berlin has filed a patent application for the use of sCPD9 as vaccine in humans. In this application, JT, NO and DK are named as inventors of sCPD9. Freie Universität Berlin is collaborating with RocketVax Inc. for further development of sCPD9 and receives funding for research. Independent of this work GN has received project funding from Biotest AG. Independent of this work MW received funding for research from Bayer Health Care, Biotest, Pantherna, Vaxxilon, and for lectures and advisory from Alexion, Aptarion, Astra Zeneca, Bayer Health Care, Berlin Chemie, Biotest, Boehringer Ingelheim, Chiesi, Glaxo Smith Kline, Insmed, Novartis, Teva and Vaxxilon. The other authors declare that they have no competing interest.

Footnotes

  • ↵* shared first authorship

  • ↵# shared last authorship

  • https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE200596

  • https://github.com/Berlin-Hamster-Single-Cell-Consortium/Live-attenuated-vaccine-strategy-confers-superior-mucosal-and-systemic-immunity-to-SARS-CoV-2

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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Posted May 16, 2022.
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A live attenuated vaccine confers superior mucosal and systemic immunity to SARS-CoV-2 variants
Geraldine Nouailles, Julia M. Adler, Peter Pennitz, Stefan Peidli, Gustavo Teixeira Alves, Morris Baumgart, Judith Bushe, Anne Voss, Alina Langenhagen, Fabian Pott, Julia Kazmierski, Cengiz Goekeri, Szandor Simmons, Na Xing, Christine Langner, Ricardo Martin Vidal, Azza Abdelgawad, Susanne Herwig, Günter Cichon, Daniela Niemeyer, Christian Drosten, Christine Goffinet, Markus Landthaler, Nils Blüthgen, Haibo Wu, Martin Witzenrath, Achim D. Gruber, Samantha D. Praktiknjo, Nikolaus Osterrieder, Emanuel Wyler, Dusan Kunec, Jakob Trimpert
bioRxiv 2022.05.16.492138; doi: https://doi.org/10.1101/2022.05.16.492138
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A live attenuated vaccine confers superior mucosal and systemic immunity to SARS-CoV-2 variants
Geraldine Nouailles, Julia M. Adler, Peter Pennitz, Stefan Peidli, Gustavo Teixeira Alves, Morris Baumgart, Judith Bushe, Anne Voss, Alina Langenhagen, Fabian Pott, Julia Kazmierski, Cengiz Goekeri, Szandor Simmons, Na Xing, Christine Langner, Ricardo Martin Vidal, Azza Abdelgawad, Susanne Herwig, Günter Cichon, Daniela Niemeyer, Christian Drosten, Christine Goffinet, Markus Landthaler, Nils Blüthgen, Haibo Wu, Martin Witzenrath, Achim D. Gruber, Samantha D. Praktiknjo, Nikolaus Osterrieder, Emanuel Wyler, Dusan Kunec, Jakob Trimpert
bioRxiv 2022.05.16.492138; doi: https://doi.org/10.1101/2022.05.16.492138

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