RT Journal Article
SR Electronic
T1 Adenovirus-Vectored SARS-CoV-2 Vaccine Expressing S1-N Fusion Protein
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.09.491179
DO 10.1101/2022.05.09.491179
A1 Muhammad S. Khan
A1 Eun Kim
A1 Alex McPherson
A1 Florian J. Weisel
A1 Shaohua Huang
A1 Thomas W. Kenniston
A1 Elena Percivalle
A1 Irene Cassaniti
A1 Fausto Baldanti
A1 Marlies Meisel
A1 Andrea Gambotto
YR 2022
UL http://biorxiv.org/content/early/2022/05/10/2022.05.09.491179.1.abstract
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.