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A linear SARS-CoV-2 DNA vaccine candidate reduces virus shedding in ferrets

View ORCID ProfileMathias Martins, Gabriela M. do Nascimento, Antonella Conforti, Jessica C.G. Noll, Joseph A. Impellizeri, Elisa Sanchez, Bettina Wagner, Lucia Lione, Erika Salvatori, Eleonora Pinto, Mirco Compagnone, Brian Viscount, James Hayward, Clay Shorrock, Luigi Aurisicchio, View ORCID ProfileDiego G. Diel
doi: https://doi.org/10.1101/2022.09.29.510112
Mathias Martins
1Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
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Gabriela M. do Nascimento
1Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
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Antonella Conforti
2Takis Biotech, Rome, Italy
3Evvivax Biotech, Rome, Italy
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Jessica C.G. Noll
1Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
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Joseph A. Impellizeri
4Veterinary Oncology Services, New York, NY, USA
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Elisa Sanchez
4Veterinary Oncology Services, New York, NY, USA
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Bettina Wagner
1Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
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Lucia Lione
2Takis Biotech, Rome, Italy
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Erika Salvatori
2Takis Biotech, Rome, Italy
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Eleonora Pinto
2Takis Biotech, Rome, Italy
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Mirco Compagnone
5Neomatrix Biotech, Rome, Italy
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Brian Viscount
6Applied DNA Sciences, Inc. New York, NY, USA
7LineaRx, Inc. New York, NY, USA
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James Hayward
6Applied DNA Sciences, Inc. New York, NY, USA
7LineaRx, Inc. New York, NY, USA
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Clay Shorrock
6Applied DNA Sciences, Inc. New York, NY, USA
7LineaRx, Inc. New York, NY, USA
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Luigi Aurisicchio
2Takis Biotech, Rome, Italy
3Evvivax Biotech, Rome, Italy
5Neomatrix Biotech, Rome, Italy
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Diego G. Diel
1Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
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  • For correspondence: dgdiel@cornell.edu
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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused more than 600 million cases and over 6 million deaths worldwide. Vaccination has been the main strategy used to contain the spread of the virus, and to avoid hospitalizations and deaths. Currently, there are two mRNA-based and one adenovirus vectored vaccines approved and available for use in the U.S. population. The versatility, low cost and rapid-to-manufacture attributes of DNA vaccines are important advantages over other platforms. However, DNA vaccination must meet higher efficiency levels for use in humans. Importantly, in vivo DNA delivery combined with electroporation (EP) has been successfully used in the veterinary field. Here we evaluated the safety, immunogenicity and protective efficacy of a novel linear SARS-CoV-2 DNA vaccine candidate for delivered by intramuscular injection followed by electroporation (Vet-ePorator™) in ferrets. The results demonstrated that the linear SARS-CoV-2 DNA vaccine candidate did not cause unexpected side effects, and was able to elicit neutralizing antibodies and T cell responses using a low dose of the linear DNA construct in prime-boost regimen, and significantly reduced shedding of infectious SARS-CoV-2 through oral and nasal secretions in a ferret model.

Competing Interest Statement

A.C. is Evvivax employee. L.L., E.S., and L.A. are Takis employees. Takis and Rottapharm Biotech are jointly developing COVID-eVax. B.V., J.H., and C.S. are Applied DNA Sciences and LineaRx employees which retain the IP of the linearDNA platform.

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 September 29, 2022.
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A linear SARS-CoV-2 DNA vaccine candidate reduces virus shedding in ferrets
Mathias Martins, Gabriela M. do Nascimento, Antonella Conforti, Jessica C.G. Noll, Joseph A. Impellizeri, Elisa Sanchez, Bettina Wagner, Lucia Lione, Erika Salvatori, Eleonora Pinto, Mirco Compagnone, Brian Viscount, James Hayward, Clay Shorrock, Luigi Aurisicchio, Diego G. Diel
bioRxiv 2022.09.29.510112; doi: https://doi.org/10.1101/2022.09.29.510112
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A linear SARS-CoV-2 DNA vaccine candidate reduces virus shedding in ferrets
Mathias Martins, Gabriela M. do Nascimento, Antonella Conforti, Jessica C.G. Noll, Joseph A. Impellizeri, Elisa Sanchez, Bettina Wagner, Lucia Lione, Erika Salvatori, Eleonora Pinto, Mirco Compagnone, Brian Viscount, James Hayward, Clay Shorrock, Luigi Aurisicchio, Diego G. Diel
bioRxiv 2022.09.29.510112; doi: https://doi.org/10.1101/2022.09.29.510112

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