Article
Full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice conferred by MVA-CoV2-S vaccine candidate
Author/s | Villadiego Luque, Francisco Javier
García-Arriaza, Juan Ramírez Lorca, Reposo García Swinburn, Roberto Cabello Rivera, Daniel Rosales Nieves, Alicia E. Muñoz Cabello, Ana María López Barneo, José Toledo Aral, Juan José |
Department | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Publication Date | 2023 |
Deposit Date | 2024-01-08 |
Published in |
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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 ... 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. |
Funding agencies | Spanish Ministry of Science and Innovation/Spanish Research Agency Red TerCel ISCIII Consejeria de Economia, Conocimiento, Empresas y Universidad Junta de Andalucia Fondo COVID-19 grant (Spanish Health Ministry, Instituto de Salud Carlos III) CSIC La CaixaImpulse grant European Commission-NextGenerationEU, through the CSIC's Global Health Platform (PTI Salud Global) European Research Council (ERC) Spanish Government Spanish Government |
Project ID. | PID2019-105995RB-I00
PID2020-114481RB-I00 RTI2018-096629-B-I00 PID2019-106410RB-I00 RD16/0011/0025 US-1380891 PECOVID-0078-2020 PY20_ 01312 COV20/00151 202120E079 2020E84 CF01-00008 PRJ201502629 AEI/10.13039/501100011033 SEV-2013-0347 SEV-2017-0712 |
Citation | Villadiego Luque, F.J., García-Arriaza, J., Ramírez Lorca, R., García Swinburn, R., Cabello Rivera, D., Rosales Nieves, A.E.,...,Toledo Aral, J.J. (2023). Full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice conferred by MVA-CoV2-S vaccine candidate. Nature neuroscience, 26 (2), 226-238. https://doi.org/10.1038/s41593-022-01242-y. |
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