tetano
Editor, Senior Moderator
Nat Neurosci
. 2023 Jan 9.
doi: 10.1038/s41593-022-01242-y. Online ahead of print.
Full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice conferred by MVA-CoV2-S vaccine candidate
Javier Villadiego[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Juan García-Arriaza[SUP] #[/SUP][SUP] 4 5 [/SUP], Reposo Ramírez-Lorca[SUP] 6 7 [/SUP], Roberto García-Swinburn[SUP] 6 7 [/SUP], Daniel Cabello-Rivera[SUP] 6 7 8 [/SUP], Alicia E Rosales-Nieves[SUP] 6 8 [/SUP], María I Álvarez-Vergara[SUP] 6 [/SUP], Fernando Cala-Fernández[SUP] 6 [/SUP], Ernesto García-Roldán[SUP] 6 [/SUP], Juan L López-Ogáyar[SUP] 6 [/SUP], Carmen Zamora[SUP] 9 [/SUP], David Astorgano[SUP] 9 [/SUP], Guillermo Albericio[SUP] 9 [/SUP], Patricia Pérez[SUP] 9 10 [/SUP], Ana M Muñoz-Cabello[SUP] 6 7 8 [/SUP], Alberto Pascual[SUP] 6 8 [/SUP], Mariano Esteban[SUP] 9 [/SUP], José López-Barneo[SUP] 6 7 8 [/SUP], Juan José Toledo-Aral[SUP] 11 12 13 [/SUP]
Affiliations
Abstract
Vaccines against SARS-CoV-2 have been shown to be safe and effective but their protective efficacy against infection in the brain is yet unclear. Here, in the susceptible transgenic K18-hACE2 mouse model of severe coronavirus disease 2019 (COVID-19), we report a spatiotemporal description of SARS-CoV-2 infection and replication through the brain. SARS-CoV-2 brain replication occurs primarily in neurons, leading to neuronal loss, signs of glial activation and vascular damage in mice infected with SARS-CoV-2. One or two doses of a modified vaccinia virus Ankara (MVA) vector expressing the SARS-CoV-2 spike (S) protein (MVA-CoV2-S) conferred full protection against SARS-CoV-2 cerebral infection, preventing virus replication in all areas of the brain and its associated damage. This protection was maintained even after SARS-CoV-2 reinfection. These findings further support the use of MVA-CoV2-S as a promising vaccine candidate against SARS-CoV-2/COVID-19.
. 2023 Jan 9.
doi: 10.1038/s41593-022-01242-y. Online ahead of print.
Full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice conferred by MVA-CoV2-S vaccine candidate
Javier Villadiego[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Juan García-Arriaza[SUP] #[/SUP][SUP] 4 5 [/SUP], Reposo Ramírez-Lorca[SUP] 6 7 [/SUP], Roberto García-Swinburn[SUP] 6 7 [/SUP], Daniel Cabello-Rivera[SUP] 6 7 8 [/SUP], Alicia E Rosales-Nieves[SUP] 6 8 [/SUP], María I Álvarez-Vergara[SUP] 6 [/SUP], Fernando Cala-Fernández[SUP] 6 [/SUP], Ernesto García-Roldán[SUP] 6 [/SUP], Juan L López-Ogáyar[SUP] 6 [/SUP], Carmen Zamora[SUP] 9 [/SUP], David Astorgano[SUP] 9 [/SUP], Guillermo Albericio[SUP] 9 [/SUP], Patricia Pérez[SUP] 9 10 [/SUP], Ana M Muñoz-Cabello[SUP] 6 7 8 [/SUP], Alberto Pascual[SUP] 6 8 [/SUP], Mariano Esteban[SUP] 9 [/SUP], José López-Barneo[SUP] 6 7 8 [/SUP], Juan José Toledo-Aral[SUP] 11 12 13 [/SUP]
Affiliations
- PMID: 36624276
- DOI: 10.1038/s41593-022-01242-y
Abstract
Vaccines against SARS-CoV-2 have been shown to be safe and effective but their protective efficacy against infection in the brain is yet unclear. Here, in the susceptible transgenic K18-hACE2 mouse model of severe coronavirus disease 2019 (COVID-19), we report a spatiotemporal description of SARS-CoV-2 infection and replication through the brain. SARS-CoV-2 brain replication occurs primarily in neurons, leading to neuronal loss, signs of glial activation and vascular damage in mice infected with SARS-CoV-2. One or two doses of a modified vaccinia virus Ankara (MVA) vector expressing the SARS-CoV-2 spike (S) protein (MVA-CoV2-S) conferred full protection against SARS-CoV-2 cerebral infection, preventing virus replication in all areas of the brain and its associated damage. This protection was maintained even after SARS-CoV-2 reinfection. These findings further support the use of MVA-CoV2-S as a promising vaccine candidate against SARS-CoV-2/COVID-19.