Summary: A new COVID-19 vaccine developed by researchers at CNB-CSIC appears to protect against brain infections and neurological symptoms associated with the coronavirus.
Source: University of Seville
Although the pathology of the respiratory system is the main impact of COVID-19, many patients also show important neurological symptoms, such as loss of smell (anosmia), headache, malaise, cognitive loss, epilepsy, ataxia and encephalopathy, among others.
However, the effect on the nervous system by the coronavirus has not been characterized in detail and it is not known whether the vaccine developed against COVID-19 prevents the spread of SARS-CoV-2 to the central nervous system and provides protection against brain injury.
Now, using a mouse model easily infected with the SARS-CoV-2 coronavirus, a multidisciplinary Spanish research team led by Dr. Javier Villadiego and Dr. Juan José Toledo-Aral (IBiS, CIBERNED and Department of Medical Physiology and Biophysics of the Faculty of Medicine of Seville) and Juan García-Arriaza (Department of Molecular and Cellular Biology CNB-CSIC, CIBERINFEC and PTI Global Health of CSIC), in collaboration with other groups from The University of Seville and the Spanish National Research Council (CSIC), showed the ability of SARS-CoV-2 to infect different areas of the brain and cause brain damage, and how the CNB-CSIC vaccine protects against brain infection.
The findings were published in Nature Neuroscience.
Researchers have studied the evolution of viral infection in different areas of the brain, noting that viral replication is mainly in neurons, producing neuropathological changes such as neuronal loss, glial activation and vascular damage.
“We have carried out a detailed anatomical-pathological and molecular study of the brain regions and cell types infected by the virus. It is amazing how the virus infects different areas and especially neurons,” said Javier Villadiego.
After the pattern of infection in the brain by SARS-CoV-2 was established, researchers evaluated the efficacy of the vaccine against COVID-19 developed at CNB-CSIC. To do this, they immunized mice with one or two doses of the MVA-CoV2-S vaccine, based on a modified Ankara vaccinia virus (MVA) that expresses the spike protein (S) of SARS-CoV-2, and analyzed its ability to do this. protect against infection and damage to the brain.
“The results obtained are spectacular, showing that the administration of a single dose of MVA-CoV2-S vaccine can prevent SARS-CoV-2 infection in all brain regions examined and prevent associated brain damage, even after re-infection with the virus. This virus showing the efficacy and immunogenic power of the vaccine that induces sterilizing immunity in the brain,” said Juan García-Arriaza.
These results reinforce previous data on the immunogenicity and efficacy of the MVA-CoV2-S vaccine in various animal models.
“Previously we have shown in a series of publications that the MVA-CoV2-S vaccine developed at CNB-CSIC caused in three animal models (rats, hamsters and monkeys) a strong immune response of antibodies that bind the S protein of the virus and neutralize antibodies against various concerns virus, as well as T-lymphocyte activation, an important marker for infection control,” said Mariano Esteban, CNB-CSIC researcher involved in the study.
These results have important long-term implications for understanding infections caused by SARS-CoV-2. “The data obtained on SARS-CoV-2 infection in the brain are compatible with the neurological pathology observed in patients with COVID-19,” said José López-Barneo, an IBiS researcher involved in the publication.
“Our work is the first study of a vaccine that is 100% effective against brain damage caused by SARS-CoV-2 in susceptible mice, and the results obtained strongly suggest that the vaccine can prevent persistent COVID-19 observed in some people infected with SARS-CoV-2,” said Juan José Toledo-Aral.
“The data presented in this study with the complete inhibition of SARS-CoV-2 replication in the brain mediated by the MVA-CoV2-S vaccine, together with previous studies published by the group and collaborators on the immunogenicity and efficacy of the vaccine against various variants of SARS -CoV-2, supporting phase I clinical trials with the vaccine, or similar prototypes, to assess safety and immunogenicity,” the study’s authors emphasized.
About this COVID-19 research news
Author: Press Office
Source: University of Seville
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Original Research: Open access.
“Complete protection against SARS-CoV-2 brain infection and damage in susceptible transgenic mice provided by the MVA-CoV2-S vaccine candidate” by Javier Villadiego et al. Nature Neuroscience
Complete protection against SARS-CoV-2 brain infection and damage in susceptible transgenic mice conferred by the vaccine candidate MVA-CoV2-S
Vaccines against SARS-CoV-2 have been shown to be safe and effective but their protective efficacy against infection in the brain is unclear.
Here, in a susceptible K18-hACE2 transgenic mouse model of severe coronavirus disease 2019 (COVID-19), we report the spatiotemporal description of SARS-CoV-2 infection and replication through the brain. Brain replication of SARS-CoV-2 is mainly in neurons, causing neuronal loss, signs of glial activation and vascular damage in mice infected with SARS-CoV-2.
One or two doses of a modified Ankara virus vaccination vector (MVA) expressing the SARS-CoV-2 spike (S) protein (MVA-CoV2-S) confers complete protection against SARS-CoV-2 cerebral infection, preventing viral replication in all brain regions and related damage. This protection was maintained even after re-infection with SARS-CoV-2.
These findings further support the use of MVA-CoV2-S as a promising vaccine candidate against SARS-CoV-2/COVID-19.