Summary: A new COVID-19 vaccine developed by researchers at CNB-CSIC appears to protect against brain infection and neurological symptoms associated with the coronavirus.
Source: University of Seville
Although respiratory system pathology is the main impact of COVID-19, many patients also exhibit important neurological symptoms such as loss of smell (anosmia), headache, malaise, cognitive loss, epilepsy, ataxia and encephalopathy, among others.
However, this effect of the coronavirus on the nervous system 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 protect against brain injury.
Now, a multidisciplinary team of Spanish researchers led by Dr. Javier Villadiego and Dr. Juan José Toledo-Aral (IBiS, CIBERNED and Department of Medical Physiology and Biophysics of the Medical Faculty of Seville) and Juan García-Arriaza (Department of Molecular and Cellular Biology of 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), 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 infection of the protects the brain.
These results were published in Nature Neuroscience.
Researchers have studied the development of viral infections in different brain regions and found that viral replication occurs mainly in neurons, leading to neuropathological changes such as neuronal loss, glial activation and vascular damage.
“We performed a very detailed anatomical-pathological and molecular study of the brain regions and cell types infected with the virus. It is remarkable how the virus infects different areas and mainly neurons,” explains Javier Villadiego.
After establishing the pattern of infection in the brain by SARS-CoV-2, the researchers evaluated the effectiveness 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, which is based on the modified vaccinia virus Ankara (MVA) expressing the spike (S) protein of SARS-CoV-2, and analyzed the ability to do so protect against infections and damage to the brain.
“The results obtained were spectacular, showing that even administering a single dose of the MVA-CoV2-S vaccine completely prevents SARS-CoV-2 infection in all brain regions examined and prevents associated brain damage, even after reinfection with the Virus. This demonstrates the great efficacy and immunogenic power of the vaccine, which induces sterilizing immunity in the brain,” says Juan García-Arriaza.
Researchers have studied the development of viral infections in different brain regions and found that viral replication occurs mainly in neurons, leading to neuropathological changes such as neuronal loss, glial activation and vascular damage. The image is in the public domain
These results support 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 we developed at CNB-CSIC induces a strong immune response in three animal models (mouse, hamster and macaque) from antibodies directed to the S protein from binding to the virus and neutralizing antibodies against different variants of the virus of concern, as well as activation of T lymphocytes, essential markers for infection control,” says Mariano Esteban, CNB-CSIC researcher involved in the study.
The findings have important long-term implications for understanding the infection caused by SARS-CoV-2. “The data we obtained on SARS-CoV-2 infection in the brain is consistent with the neurological pathology observed in patients with COVID-19,” says José López-Barneo, IBiS researcher working at the publication was involved.
“Our work is the first study of a vaccine that is 100% effective against SARS-CoV-2 brain damage in a susceptible mouse, and the results obtained strongly suggest that the vaccine could prevent the ongoing COVID-19 , which has been observed in several people infected 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 conducted by the group and collaborators on the immunogenicity and efficacy of the vaccine against Various variants of SARS-CoV-2 have been published, supporting phase I clinical trials with such a vaccine or similar prototypes to assess their safety and immunogenicity,” the study authors emphasize.
About this COVID-19 research news
Author: press office
Source: University of Seville
Contact: Press Office – University of Seville
Picture: The image is in the public domain
See also
Original research: Open access.
“Complete Protection from SARS-CoV-2 Brain Infection and Damage in Susceptible Transgenic Mice Conferred by the MVA-CoV2-S Vaccine Candidate” by Javier Villadiego et al. nature neuroscience
abstract
Complete Protection from SARS-CoV-2 Brain Infection and Damage in Susceptible Transgenic Mice by MVA-CoV2-S Vaccine Candidate
Vaccines against SARS-CoV-2 have been shown to be safe and effective, but their protective effect against infections in the brain is still unclear.
Here we report a spatiotemporal description of SARS-CoV-2 infection and replication through the brain in the susceptible K18-hACE2 transgenic mouse model of severe coronavirus disease 2019 (COVID-19). Replication of SARS-CoV-2 in the brain occurs primarily in neurons, resulting in 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 cerebral SARS-CoV-2 infection and prevented viral replication from overall areas of the brain and the associated damage. This protection was maintained even after a SARS-CoV-2 reinfection.
These results support the use of MVA-CoV2-S as a promising vaccine candidate against SARS-CoV-2/COVID-19.