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Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice

View ORCID ProfileAndrea N. Loes, View ORCID ProfileLauren E. Gentles, View ORCID ProfileAllison J. Greaney, View ORCID ProfileKatharine H. D. Crawford, View ORCID ProfileJesse D. Bloom
doi: https://doi.org/10.1101/2020.08.12.248823
Andrea N. Loes
1Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
2Howard Hughes Medical Institute, Seattle, WA 98103, USA
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Lauren E. Gentles
1Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
3Department of Microbiology, University of Washington, Seattle, WA 98195-7735, USA
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Allison J. Greaney
1Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
4Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
5Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA
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Katharine H. D. Crawford
1Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
4Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
5Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA
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Jesse D. Bloom
1Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
2Howard Hughes Medical Institute, Seattle, WA 98103, USA
3Department of Microbiology, University of Washington, Seattle, WA 98195-7735, USA
4Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
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  • For correspondence: jbloom@fredhutch.org
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Abstract

An effective vaccine is essential to controlling the spread of SARS-CoV-2 virus. Here, we describe an influenza-virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 Spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:250). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for production of influenza vaccines.

Competing Interest Statement

The authors have declared no competing interest.

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 August 13, 2020.
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Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice
Andrea N. Loes, Lauren E. Gentles, Allison J. Greaney, Katharine H. D. Crawford, Jesse D. Bloom
bioRxiv 2020.08.12.248823; doi: https://doi.org/10.1101/2020.08.12.248823
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Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice
Andrea N. Loes, Lauren E. Gentles, Allison J. Greaney, Katharine H. D. Crawford, Jesse D. Bloom
bioRxiv 2020.08.12.248823; doi: https://doi.org/10.1101/2020.08.12.248823

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