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bioRxiv · 10.1101/2022.05.09.491179

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

Khan, M. S.·Kim, E.·McPherson, A.·Weisel, F. J.·Huang, S.·Kenniston, T. W.·Percivalle, E.·Gambotto, A.·Baldanti, F.·Meisel, M.
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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 (1x1010 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.

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Khan, M. S., Kim, E., McPherson, A., Weisel, F. J., Huang, S., Kenniston, T. W., Percivalle, E., Gambotto, A., Baldanti, F., Meisel, M.. 2022-05-10. Adenovirus-Vectored SARS-CoV-2 Vaccine Expressing S1-N Fusion Protein. https://doi.org/10.1101/2022.05.09.491179

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