Pre-Clinical Testing of Two Serologically Distinct Chimpanzee-Origin Adenovirus Vectors Expressing Spike of SARS-CoV-2

Новиков, Михаил С.; Hasanpourghadi, Mohadeseh; Ambrose, Robert O.; Chekaoui, Arezki; Newman, Dakota; Giles-Davis, Wynetta; Xiang, Zhiquan; Zhou, Xiangyang; Ertl, Hildegund C. J.

doi:10.2139/ssrn.4059223

Cited by 1 publication

(1 citation statement)

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“…Whether this reflects increased T help due to responses to the N protein or a difference in vector dosing with group 2 hamsters receiving double the dose of the AdC-S vector is unknown. As expected, and reported by others, VNAs cross-reacted albeit with significantly reduced activity against viral variants of concern [45–47].…”

Section: Discussionsupporting

confidence: 88%

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

Novikov

Ambrose

et al. 2022

Preprint

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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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Section: Discussionsupporting

confidence: 88%