Cell
Volume 183, Issue 1, 1 October 2020, Pages 169-184.e13
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Article
A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2

https://doi.org/10.1016/j.cell.2020.08.026Get rights and content
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Highlights

  • Chimpanzee adenoviral vaccines encoding stabilized S induce neutralizing Abs

  • Chimpanzee adenoviral vaccines protect against SARS-CoV-2 infection and pneumonia

  • Intranasal vaccine delivery generates robust mucosal B and T cell responses

  • Intranasal ChAd-SARS-CoV-2 prevents upper and lower respiratory tract infection

Summary

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 prefusion 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 neutralizing antibodies, promotes systemic and mucosal immunoglobulin A (IgA) and T cell responses, and almost entirely prevents SARS-CoV-2 infection in both the upper and lower respiratory tracts. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission and curtailing pandemic spread.

Keywords

vaccine
SARS-CoV-2
COVID-19
mucosal immunity
IgA
intranasal
protection
pathogenesis
antibody
T cells

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