PT  - JOURNAL ARTICLE
AU  - Muhammad S. Khan
AU  - Eun Kim
AU  - Alex McPherson
AU  - Florian J. Weisel
AU  - Shaohua Huang
AU  - Thomas W. Kenniston
AU  - Elena Percivalle
AU  - Irene Cassaniti
AU  - Fausto Baldanti
AU  - Marlies Meisel
AU  - Andrea Gambotto
TI  - Adenovirus-Vectored SARS-CoV-2 Vaccine Expressing S1-N Fusion Protein
AID  - 10.1101/2022.05.09.491179
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.09.491179
4099  - http://biorxiv.org/content/early/2022/05/10/2022.05.09.491179.1.short
4100  - http://biorxiv.org/content/early/2022/05/10/2022.05.09.491179.1.full
AB  - 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 StatementThe authors have declared no competing interest.