tetano
Editor, Senior Moderator
Hum Vaccin Immunother
. 2022 Oct 4;2127292.
doi: 10.1080/21645515.2022.2127292. Online ahead of print.
A single intranasal administration of AdCOVID protects against SARS-CoV-2 infection in the upper and lower respiratory tracts
Michael D Schultz[SUP] 1 [/SUP], John J Suschak[SUP] 2 [/SUP], Davide Botta[SUP] 1 [/SUP], Aaron Silva-Sanchez[SUP] 3 [/SUP], R Glenn King[SUP] 1 [/SUP], Thomas W Detchemendy[SUP] 4 [/SUP], Chetan D Meshram[SUP] 5 [/SUP], Jeremy B Foote[SUP] 1 [/SUP], Fen Zhou[SUP] 1 [/SUP], Jennifer L Tipper[SUP] 5 [/SUP], Jianfeng Zhang[SUP] 2 [/SUP], Kevin S Harrod[SUP] 5 [/SUP], Sixto M Leal Jr[SUP] 4 [/SUP], Troy D Randall[SUP] 3 [/SUP], M Scot Roberts[SUP] 2 [/SUP], Bertrand Georges[SUP] 2 [/SUP], Frances E Lund[SUP] 1 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; SARS-CoV-2; adenovirus vector; intranasal; mucosal immunity; receptor binding domain; vaccine; viral vector.
. 2022 Oct 4;2127292.
doi: 10.1080/21645515.2022.2127292. Online ahead of print.
A single intranasal administration of AdCOVID protects against SARS-CoV-2 infection in the upper and lower respiratory tracts
Michael D Schultz[SUP] 1 [/SUP], John J Suschak[SUP] 2 [/SUP], Davide Botta[SUP] 1 [/SUP], Aaron Silva-Sanchez[SUP] 3 [/SUP], R Glenn King[SUP] 1 [/SUP], Thomas W Detchemendy[SUP] 4 [/SUP], Chetan D Meshram[SUP] 5 [/SUP], Jeremy B Foote[SUP] 1 [/SUP], Fen Zhou[SUP] 1 [/SUP], Jennifer L Tipper[SUP] 5 [/SUP], Jianfeng Zhang[SUP] 2 [/SUP], Kevin S Harrod[SUP] 5 [/SUP], Sixto M Leal Jr[SUP] 4 [/SUP], Troy D Randall[SUP] 3 [/SUP], M Scot Roberts[SUP] 2 [/SUP], Bertrand Georges[SUP] 2 [/SUP], Frances E Lund[SUP] 1 [/SUP]
Affiliations
- PMID: 36194255
- DOI: 10.1080/21645515.2022.2127292
Abstract
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.
Keywords: COVID-19; SARS-CoV-2; adenovirus vector; intranasal; mucosal immunity; receptor binding domain; vaccine; viral vector.