Summary: A new COVID-19 vaccine developed by CNB-CSIC researchers appears to protect against brain infection and neurological symptoms associated with the coronavirus.
Source: University of Seville
Although respiratory system pathology is the primary impact of COVID-19, many patients also experience significant neurological symptoms, such as loss of sense of smell (anosmia), headache, malaise, cognitive loss, epilepsy, ataxia and encephalopathy, among others.
However, this effect on the nervous system by the coronavirus has not been characterized in detail and it is not known whether the vaccines developed against COVID-19 prevent the spread of SARS-CoV-2 to the central nervous system and confer protection. against brain damage.
Now, using a mouse model susceptible to infection with the SARS-CoV-2 coronavirus, a multidisciplinary team of Spanish researchers led by Dr. Javier Villadiego and Dr. Juan José Toledo-Aral (IBiS, CIBERNED and Department of Physiology Medicine and Biophysics of the Faculty of Medicine of Seville) and Juan García-Arriaza (Department of Molecular and Cellular Biology of the CNB-CSIC, CIBERINFEC and PTI Global Health of the CSIC), in collaboration with other groups of the University of Seville and from the Spanish National Research Council (CSIC), demonstrate the ability of SARS-CoV-2 to infect different regions of the brain and cause brain damage, and how the CNB-CSIC vaccine fully protects against brain infection.
These findings are published in Natural neuroscience.
The researchers studied the course of viral infection in different regions of the brain, noting that viral replication occurs mainly in neurons, producing neuropathological alterations such as neuronal loss, glial activation and vascular damage.
“We carried out a very detailed anatomo-pathological and molecular study of the regions of the brain and the types of cells that were infected by the virus. It is remarkable how the virus infects different areas and mainly neurons,” explains Javier Villadiego.
Once the brain infection pattern of SARS-CoV-2 was established, researchers assessed the efficacy of the COVID-19 vaccine developed at CNB-CSIC. To do this, they immunized mice with one or two doses of the MVA-CoV2-S vaccine, based on the modified vaccinia virus Ankara (MVA) expressing the spike (S) protein of SARS-CoV-2, and analyzed the ability to protect against infection and brain damage.
“The results obtained were spectacular, demonstrating that even the administration of a single dose of the MVA-CoV2-S vaccine completely prevents SARS-CoV-2 infection in all brain regions studied and prevents associated brain damage. , even after reinfection with the virus. This demonstrates the high efficacy and immunogenic power of the vaccine which induces sterilizing immunity in the brain,” says Juan García-Arriaza.
These results reinforce previous data on the immunogenicity and efficacy of the MVA-CoV2-S vaccine in various animal models.
“We had previously shown in a series of publications that the MVA-CoV2-S vaccine that we developed at the CNB-CSIC induces in three animal models (mouse, hamster and macaque) a potent immune response of antibodies binding to the protein S of the virus and neutralizing antibodies against different worrying variants of the virus, as well as the activation of T lymphocytes, essential markers for the control of the infection”, explains Mariano Esteban, researcher at the CNB-CSIC involved in the study. .
The findings have important long-term implications for understanding infection caused by SARS-CoV-2. “The data we obtained on SARS-CoV-2 infection in the brain are consistent with the neurological pathology observed in patients with COVID-19,” says José López-Barneo, IBiS researcher who participated 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 a susceptible mouse, and the results obtained strongly suggest that the vaccine could prevent the persistence of the observed COVID-19. in several infected people. with SARS-CoV-2,” says Juan José Toledo-Aral.
“The data provided in this study with 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 immunogenicity and vaccine efficacy against different variants of SARS-CoV-2, support phase I clinical trials with such a vaccine, or similar prototypes, to assess their safety and immunogenicity,” the study authors point out.
About this COVID-19 research news
Author: Press office
Source: University of Seville
Contact: Press office – University of Seville
Picture: Image is in public domain
Original research: Free access.
“Complete protection against brain infection and damage caused by SARS-CoV-2 in susceptible transgenic mice conferred by the MVA-CoV2-S vaccine candidate” by Javier Villadiego et al. Natural neuroscience
Complete protection against brain infection and damage caused by SARS-CoV-2 in susceptible transgenic mice conferred by the MVA-CoV2-S vaccine candidate
SARS-CoV-2 vaccines have been shown to be safe and effective, but their protective efficacy against infection in the brain is not yet clear.
Here, in the susceptible K18-hACE2 transgenic mouse model of severe coronavirus disease 2019 (COVID-19), we report a spatiotemporal description of SARS-CoV-2 infection and replication across the brain. . Brain replication of SARS-CoV-2 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 spike (S) protein of SARS-CoV-2 (MVA-CoV2-S) conferred complete protection against brain infection by SARS-CoV-2, preventing the replication of the virus in all areas of the brain and its associated damage. This protection was maintained even after reinfection with SARS-CoV-2.
These results further support the use of MVA-CoV2-S as a promising vaccine candidate against SARS-CoV-2/COVID-19.