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Inhalable Nanobody (PiN-21) prevents and treats SARS-CoV-2 infections in Syrian hamsters at ultra-low doses

Sham Nambulli, Yufei Xiang, Natasha L. Tilston-Lunel, Linda J. Rennick, Zhe Sang, William B. Klimstra, Douglas S. Reed, Nicholas A. Crossland, Yi Shi, W. Paul Duprex
doi: https://doi.org/10.1101/2021.02.23.432569
Sham Nambulli
1Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA
2Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA
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Yufei Xiang
3Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA
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Natasha L. Tilston-Lunel
1Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA
2Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA
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Linda J. Rennick
1Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA
2Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA
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Zhe Sang
3Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA
4University of Pittsburgh–Carnegie Mellon University Program in Computational Biology, Pittsburgh, PA, USA
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William B. Klimstra
1Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA
2Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA
5Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA
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Douglas S. Reed
1Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA
5Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA
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Nicholas A. Crossland
6Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
7National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, USA
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Yi Shi
3Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA
4University of Pittsburgh–Carnegie Mellon University Program in Computational Biology, Pittsburgh, PA, USA
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  • For correspondence: yi.shi@pitt.edu pduprex@pitt.edu
W. Paul Duprex
1Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA
2Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA
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  • For correspondence: yi.shi@pitt.edu pduprex@pitt.edu
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Abstract

Globally there is an urgency to develop effective, low-cost therapeutic interventions for coronavirus disease 2019 (COVID-19). We previously generated the stable and ultrapotent homotrimeric Pittsburgh inhalable Nanobody 21 (PiN-21). Using Syrian hamsters that model moderate to severe COVID-19 disease, we demonstrate the high efficacy of PiN-21 to prevent and treat SARS-CoV-2 infection. Intranasal delivery of PiN-21 at 0.6 mg/kg protects infected animals from weight loss and substantially reduces viral burdens in both lower and upper airways compared to control. Aerosol delivery of PiN-21 facilitates deposition throughout the respiratory tract and dose minimization to 0.2 mg/kg. Inhalation treatment quickly reverses animals’ weight loss post-infection and decreases lung viral titers by 6 logs leading to drastically mitigated lung pathology and prevents viral pneumonia. Combined with the marked stability and low production cost, this novel therapy may provide a convenient and cost-effective option to mitigate the ongoing pandemic.

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. All rights reserved. No reuse allowed without permission.
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Posted February 23, 2021.
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Inhalable Nanobody (PiN-21) prevents and treats SARS-CoV-2 infections in Syrian hamsters at ultra-low doses
Sham Nambulli, Yufei Xiang, Natasha L. Tilston-Lunel, Linda J. Rennick, Zhe Sang, William B. Klimstra, Douglas S. Reed, Nicholas A. Crossland, Yi Shi, W. Paul Duprex
bioRxiv 2021.02.23.432569; doi: https://doi.org/10.1101/2021.02.23.432569
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Inhalable Nanobody (PiN-21) prevents and treats SARS-CoV-2 infections in Syrian hamsters at ultra-low doses
Sham Nambulli, Yufei Xiang, Natasha L. Tilston-Lunel, Linda J. Rennick, Zhe Sang, William B. Klimstra, Douglas S. Reed, Nicholas A. Crossland, Yi Shi, W. Paul Duprex
bioRxiv 2021.02.23.432569; doi: https://doi.org/10.1101/2021.02.23.432569

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