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. Epub 2020 Aug 19.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoviridae / genetics
  • Administration, Intranasal
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • COVID-19
  • COVID-19 Vaccines
  • Chlorocebus aethiops
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / pathology
  • Coronavirus Infections / prevention & control
  • Female
  • HEK293 Cells
  • Humans
  • Immunogenicity, Vaccine*
  • Injections, Intramuscular
  • Mice
  • Mice, Inbred BALB C
  • Pandemics
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / pathology
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / pathology
  • Respiratory Mucosa / virology
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology
  • Vero Cells
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines
  • spike glycoprotein, SARS-CoV