A single intranasal dose of chimpanzee adenovirus-vectored vaccine confers sterilizing immunity against SARS-CoV-2 infection

Hassan, A. O.; Kafai, N. M.; Dmitriev, I. P.; Fox, J. M.; Smith, B.; Harvey, I. B.; Chen, R. E.; Winkler, E. S.; Wessel, A. W.; Case, J. B.; Kashentseva, E.; McCune, B. T.; Bailey, A. L.; Zhao, H.; VanBlargan, L. A.; Dai, Y.; Ma, M.; Adams, L. J.; Shrihari, S.; Gralinski, L. E.; Hou, Y. J.; Schaefer, A.; Kim, A. S.; Keeler, S. P.; Weiskopf, D.; Baric, R. S.; Holtzman, M. J.; Fremont, D. H.; Curiel, D. T.; Diamond, M. S.

doi:10.1101/2020.07.16.205088

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bioRxiv · 10.1101/2020.07.16.205088

A single intranasal dose of chimpanzee adenovirus-vectored vaccine confers sterilizing immunity against SARS-CoV-2 infection

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Abstract

The Coronavirus Disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of systemic and mucosal IgA and T cell responses, completely prevents SARS-CoV-2 infection in the upper and lower respiratory tracts, and likely confers sterilizing immunity in most animals. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission, and curtailing pandemic spread.

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Hassan, A. O., Kafai, N. M., Dmitriev, I. P., Fox, J. M., Smith, B., Harvey, I. B., Chen, R. E., Winkler, E. S., Wessel, A. W., Case, J. B., Kashentseva, E., McCune, B. T., Bailey, A. L., Zhao, H., VanBlargan, L. A., Dai, Y., Ma, M., Adams, L. J., Shrihari, S., Gralinski, L. E., Hou, Y. J., Schaefer, A., Kim, A. S., Keeler, S. P., Weiskopf, D., Baric, R. S., Holtzman, M. J., Fremont, D. H., Curiel, D. T., Diamond, M. S.. 2020-07-17. A single intranasal dose of chimpanzee adenovirus-vectored vaccine confers sterilizing immunity against SARS-CoV-2 infection. https://doi.org/10.1101/2020.07.16.205088

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