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

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

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: dcuriel@wustl.edu.
  • 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: diamond@wusm.wustl.edu.
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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