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Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection

Moore, A. C.; Dora, E. G.; Peinovich, N.; Tucker, K. P.; Lin, K.; Cortese, M.; Tucker, S.

2020-09-06 immunology
10.1101/2020.09.04.283853 bioRxiv
Show abstract

There is an urgent need to develop efficacious vaccines against SARS-CoV-2 that also address the issues of deployment, equitable access, and vaccine acceptance. Ideally, the vaccine would prevent virus infection and transmission as well as preventing COVID-19 disease. We previously developed an oral adenovirus-based vaccine technology that induces both mucosal and systemic immunity in humans. Here we investigate the immunogenicity of a range of candidate adenovirusbased vaccines, expressing full or partial sequences of the spike and nucleocapsid proteins, in mice. We demonstrate that, compared to expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and in the lungs, when the vaccine is administered mucosally. Antigen-specific CD4+ and CD8+ T cells were induced by this leading vaccine candidate at low and high doses. This fulllength spike antigen plus nucleocapsid adenovirus construct has been prioritized for further clinical development.

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