Single immunization with recombinant ACAM2000 vaccinia viruses expressing the spike and the nucleocapsid proteins protect hamsters against SARS-CoV-2 caused clinical disease

Cao, J.; Deschambault, Y.; Lynch, J.; Warner, B.; Tierney, K.; Huynh, D.; Vendramelli, R.; Tailor, N.; Booth, S.; Sajesh, B.; Frost, K.; LeBlanc, K.; Layne, C.; Lin, L.; Beniac, D.; Carpenter, M.; Safronetz, D.; Li, X.; Kobasa, D.

doi:10.1101/2021.12.02.470987

bioRxiv · 10.1101/2021.12.02.470987

Single immunization with recombinant ACAM2000 vaccinia viruses expressing the spike and the nucleocapsid proteins protect hamsters against SARS-CoV-2 caused clinical disease

Cao, J.·Deschambault, Y.·Lynch, J.·Warner, B.·Tierney, K.·Huynh, D.·Vendramelli, R.·Tailor, N.·Booth, S.·Sajesh, B.·Frost, K.·LeBlanc, K.·Layne, C.·Lin, L.·Beniac, D.·Carpenter, M.·Safronetz, D.·Li, X.·Kobasa, D.

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Abstract

Increasing cases of SARS-CoV-2 breakthrough infections from immunization with predominantly spike protein based COVID-19 vaccines highlight the need for alternative vaccines using different platforms and/or antigens. In this study, we expressed SARS-CoV-2 spike and nucleocapsid proteins in a novel vaccinia virus ACAM2000 platform (rACAM2000). Following a single intramuscular immunization, the rACAM2000 co-expressing the spike and nucleocapsid proteins induced significantly improved protection against SARS-CoV-2 challenge in comparison to rACAM2000 expressing the individual proteins in a hamster model, as shown by reduced weight loss and quicker recovery time. The protection was associated with reduced viral loads, increased neutralizing antibody titre and reduced neutrophil-to-lymphocyte ratio. Thus, our study demonstrates that the rACAM2000 expressing a combination of the spike and nucleocapsid antigens is a promising COVID-19 vaccine candidate and further studies will investigate if the rACAM2000 vaccine candidate can induce a long lasting immunity against infection of SARS-CoV-2 variants of concern.

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Cao, J., Deschambault, Y., Lynch, J., Warner, B., Tierney, K., Huynh, D., Vendramelli, R., Tailor, N., Booth, S., Sajesh, B., Frost, K., LeBlanc, K., Layne, C., Lin, L., Beniac, D., Carpenter, M., Safronetz, D., Li, X., Kobasa, D.. 2021-12-03. Single immunization with recombinant ACAM2000 vaccinia viruses expressing the spike and the nucleocapsid proteins protect hamsters against SARS-CoV-2 caused clinical disease. https://doi.org/10.1101/2021.12.02.470987

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