A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2

  • Cell. 2020 Oct 1;183(1):169-184.e13. doi: 10.1016/j.cell.2020.08.026.
Ahmed O Hassan  1 ,  Natasha M Kafai  2 ,  Igor P Dmitriev  3 ,  Julie M Fox  1 ,  Brittany K Smith  4 ,  Ian B Harvey  5 ,  Rita E Chen  2 ,  Emma S Winkler  2 ,  Alex W Wessel  2 ,  James Brett Case  1 ,  Elena Kashentseva  3 ,  Broc T McCune  1 ,  Adam L Bailey  5 ,  Haiyan Zhao  5 ,  Laura A VanBlargan  1 ,  Ya-Nan Dai  5 ,  Meisheng Ma  5 ,  Lucas J Adams  5 ,  Swathi Shrihari  1 ,  Jonathan E Danis  5 ,  Lisa E Gralinski  6 ,  Yixuan J Hou  6 ,  Alexandra Schäfer  6 ,  Arthur S Kim  2 ,  Shamus P Keeler  7 ,  Daniela Weiskopf  8 ,  Ralph S Baric  9 ,  Michael J Holtzman  10 ,  Daved H Fremont  11 ,  David T Curiel  12 ,  Michael S Diamond  13
Affiliations
  • 1. Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 2. Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 3. Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 4. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 5. Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 6. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • 7. Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 8. Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • 9. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • 10. Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 11. Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 12. Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: [email protected].
  • 13. Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: [email protected].
PMID: 32931734 DOI: 10.1016/j.cell.2020.08.026
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 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
COVID-19; IgA; SARS-CoV-2; T cells; antibody; intranasal; mucosal immunity; pathogenesis; protection; vaccine.
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