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Adenovirus-Vectored SARS-CoV-2 Vaccine Expressing S1-N Fusion Protein

View ORCID ProfileMuhammad S. Khan, Eun Kim, Alex McPherson, Florian J. Weisel, Shaohua Huang, Thomas W. Kenniston, Elena Percivalle, Irene Cassaniti, Fausto Baldanti, Marlies Meisel, View ORCID ProfileAndrea Gambotto
doi: https://doi.org/10.1101/2022.05.09.491179
Muhammad S. Khan
aDepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, PA 15213, USA
bDepartment of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
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  • ORCID record for Muhammad S. Khan
Eun Kim
aDepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, PA 15213, USA
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Alex McPherson
bDepartment of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
cDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA
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Florian J. Weisel
cDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA
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Shaohua Huang
aDepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, PA 15213, USA
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Thomas W. Kenniston
aDepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, PA 15213, USA
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Elena Percivalle
dMolecular Virology Unit, Microbiology and Virology Department, IRCCS Policlinico San Matteo, Via Taramelli 5, 27100 Pavia, Italy
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Irene Cassaniti
dMolecular Virology Unit, Microbiology and Virology Department, IRCCS Policlinico San Matteo, Via Taramelli 5, 27100 Pavia, Italy
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Fausto Baldanti
dMolecular Virology Unit, Microbiology and Virology Department, IRCCS Policlinico San Matteo, Via Taramelli 5, 27100 Pavia, Italy
eDepartment of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
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Marlies Meisel
bDepartment of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
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Andrea Gambotto
aDepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, PA 15213, USA
bDepartment of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
fUPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA
gDepartment of Medicine, Division of Infectious Disease, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
hDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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  • For correspondence: gambottoa@upmc.edu
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Abstract

Additional COVID-19 vaccines that are safe, easy to manufacture, and immunogenic are needed for global vaccine equity. Here, we developed a recombinant type 5 adenovirus vector encoding for the SARS-CoV-2-S1 subunit antigen and nucleocapsid as a fusion protein (Ad5.SARS-CoV-2-S1N) delivered to BALB/c mice through multiple vaccine administration routes. A single subcutaneous (S.C.) immunization with Ad5.SARS-CoV-2-S1N induced a similar humoral response, along with a significantly higher S1-specific cellular response, as a recombinant type 5 adenovirus vector encoding for S1 alone (Ad5.SARS-CoV-2-S1). Immunogenicity was improved by homologous prime boost strategies, using either S.C. or intranasal (I.N.) delivery of Ad5.SARS-CoV-2-S1N, and further improved through heterologous prime boost, with traditional intramuscular (I.M.) injection, using subunit recombinant S1 protein. Priming with low dose (1×1010 v.p.) of Ad5.SARS-CoV-2-S1N and boosting with either wildtype recombinant rS1 or B.1.351 recombinant rS1 induced a robust neutralizing response, that was sustained against immune evasive Beta and Gamma SARS-CoV-2 variants, along with a long-lived plasma cell response in the bone marrow 29 weeks post vaccination. This novel Ad5-vectored SARS-CoV-2 vaccine candidate showed promising immunogenicity in mice and supports the further development of COVID-19 based vaccines incorporating the nucleoprotein as a target antigen.

Competing Interest Statement

The authors have declared no competing interest.

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Adenovirus-Vectored SARS-CoV-2 Vaccine Expressing S1-N Fusion Protein
Muhammad S. Khan, Eun Kim, Alex McPherson, Florian J. Weisel, Shaohua Huang, Thomas W. Kenniston, Elena Percivalle, Irene Cassaniti, Fausto Baldanti, Marlies Meisel, Andrea Gambotto
bioRxiv 2022.05.09.491179; doi: https://doi.org/10.1101/2022.05.09.491179
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Adenovirus-Vectored SARS-CoV-2 Vaccine Expressing S1-N Fusion Protein
Muhammad S. Khan, Eun Kim, Alex McPherson, Florian J. Weisel, Shaohua Huang, Thomas W. Kenniston, Elena Percivalle, Irene Cassaniti, Fausto Baldanti, Marlies Meisel, Andrea Gambotto
bioRxiv 2022.05.09.491179; doi: https://doi.org/10.1101/2022.05.09.491179

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