Human Vaccines & Immunotherapeutics (Nov 2022)

A single intranasal administration of AdCOVID protects against SARS-CoV-2 infection in the upper and lower respiratory tracts

  • Michael D. Schultz,
  • John J. Suschak,
  • Davide Botta,
  • Aaron Silva-Sanchez,
  • R. Glenn King,
  • Thomas W. Detchemendy,
  • Chetan D. Meshram,
  • Jeremy B. Foote,
  • Fen Zhou,
  • Jennifer L. Tipper,
  • Jianfeng Zhang,
  • Kevin S. Harrod,
  • Sixto M. Leal,
  • Troy D. Randall,
  • M. Scot Roberts,
  • Bertrand Georges,
  • Frances E. Lund

DOI
https://doi.org/10.1080/21645515.2022.2127292
Journal volume & issue
Vol. 18, no. 6

Abstract

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The coronavirus disease 2019 (COVID-19) pandemic has illustrated the critical need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive approach for preventing COVID-19 as the nasal mucosa is the site of initial SARS-CoV-2 entry and viral replication prior to aspiration into the lungs. We previously demonstrated that a single intranasal administration of a candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain of the SARS-CoV-2 spike protein (AdCOVID) induced robust immunity in both the airway mucosa and periphery, and completely protected K18-hACE2 mice from lethal SARS-CoV-2 challenge. Here we show that a single intranasal administration of AdCOVID limits viral replication in the nasal cavity of K18-hACE2 mice. AdCOVID also induces sterilizing immunity in the lungs of mice as reflected by the absence of infectious virus. Finally, AdCOVID prevents SARS-CoV-2 induced pathological damage in the lungs of mice. These data show that AdCOVID not only limits viral replication in the respiratory tract, but it also prevents virus-induced inflammation and immunopathology following SARS-CoV-2 infection.

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