Prime-boost vaccinations with two serologically distinct chimpanzee adenovirus vectors expressing SARS-CoV-2 spike or nucleocapsid tested in a hamster COVID-19 model

Hasanpourghadi, M.; Novikov, M.; Ambrose, R.; Chekaoui, A.; Newman, D.; Ding, J.; Giles-Davis, W.; Xiang, Z.; Zhou, X.; Liu, Q.; Swagata, K.; Ertl, H. C. J.

doi:10.1101/2022.03.17.484786

bioRxiv · 10.1101/2022.03.17.484786

Prime-boost vaccinations with two serologically distinct chimpanzee adenovirus vectors expressing SARS-CoV-2 spike or nucleocapsid tested in a hamster COVID-19 model

Hasanpourghadi, M.·Novikov, M.·Ambrose, R.·Chekaoui, A.·Newman, D.·Ding, J.·Giles-Davis, W.·Xiang, Z.·Zhou, X.·Liu, Q.·Swagata, K.·Ertl, H. C. J.

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Abstract

Two serologically distinct replication-defective chimpanzee-origin adenovirus (Ad) vectors (AdC) called AdC6 and AdC7 expressing the spike (S) or nucleocapsid (N) proteins of an early SARS-CoV-2 isolate were tested individually or as a mixture in a hamster COVID-19 challenge model. The N protein, which was expressed as a fusion protein within herpes simplex virus glycoprotein D (gD) stimulated antibodies and CD8+ T cells. The S protein expressing AdC (AdC-S) vectors induced antibodies including those with neutralizing activity that in part cross-reacted with viral variants. Hamsters vaccinated with the AdC-S vectors were protected against serious disease and showed accelerated recovery upon SARS-CoV-2 challenge. Protection was enhanced if AdC-S vectors were given together with the AdC vaccines that expressed the gDN fusion protein (AdC-gDN). In contrast hamsters that just received the AdC-gDN vaccines showed only marginal lessening of symptoms compared to control animals. These results indicate that immune response to the N protein that is less variable that the S protein may potentiate and prolong protection achieved by the currently used genetic COVID-19 vaccines.

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Hasanpourghadi, M., Novikov, M., Ambrose, R., Chekaoui, A., Newman, D., Ding, J., Giles-Davis, W., Xiang, Z., Zhou, X., Liu, Q., Swagata, K., Ertl, H. C. J.. 2022-03-18. Prime-boost vaccinations with two serologically distinct chimpanzee adenovirus vectors expressing SARS-CoV-2 spike or nucleocapsid tested in a hamster COVID-19 model. https://doi.org/10.1101/2022.03.17.484786

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