COVID-19 vaccine that protects against infection and brain damage caused by the virus

Although the pathology of the respiratory system is the main affectation of the COVID-19 disease, caused by the SARS-CoV-2 coronavirus, many of the patients manifest important neurological symptoms, such as loss of smell (anosmia), headaches, malaise general, cognitive loss, epilepsy, ataxia and encephalopathy, among others. However, this affectation of the nervous system by the coronavirus has not been characterized in detail and it is unknown if the vaccines developed against COVID-19 prevent the spread of SARS-CoV-2 to the central nervous system and confer protection against infections. brain injuries.

Now, using a mouse model susceptible to infection by the SARS-CoV-2 coronavirus, a multidisciplinary team of Spanish researchers led by doctors Javier Villadiego and Juan José Toledo Aral (from the Seville Institute of Biomedicine (IBiS) in Spain and other institutions) and Juan García Arriaza (from the National Center for Biotechnology (CNB) attached to the Higher Council for Scientific Research (CSIC) of Spain and other institutions), in collaboration with other groups from the University of Seville and the CSIC, demonstrate the ability of SARS-CoV-2 to infect different regions of the brain and cause brain damage, and how the vaccine created at the CNB completely protects against said infection in the brain.

The authors of the study have studied the evolution of the viral infection in different brain regions, noting that virus replication occurs mainly in neurons, producing neuropathological alterations such as neuronal loss, glial activation, and vascular damage. “We have carried out a very detailed anatomo-pathological and molecular study of the brain regions and types of cells that have been infected by the virus, and it is remarkable how the virus mostly infects neurons in different areas”, explains Javier Villadiego.

Once the pattern of infection in the brain by SARS-CoV-2 was established, the researchers evaluated the efficacy of the vaccine against COVID-19 developed by the CNB. To do this, they immunized mice with one or two doses of the vaccine (MVA-CoV2-S), based on the modified vaccinia virus from Ankara (MVA) expressing the spike (S) protein of SARS-CoV-2, and analyzed the ability to protect against infection and damage in the brain. “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 a reinfection with the virus, which demonstrates the great efficacy and immunogenic power of the vaccine that induces sterilizing immunity in the brain”, as Juan García Arriaza indicates.

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 powerful immunological response of antibodies binding to the S protein of 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, a CNB researcher involved in the study.

The generated results have important long-term implications for understanding the infection caused by SARS-CoV-2. “The data we have obtained on SARS-CoV-2 infection in the brain are compatible with the neurological pathology observed in patients with COVID-19”, highlights José López Barneo, an IBiS researcher who participated in the study. “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 persistent COVID-19. observed in many people infected with SARS-CoV-2”, highlights Juan José Toledo Aral.

A: neuron of the cerebral cortex infected with the SARS-CoV-2 coronavirus (viral particles in green). B and C: in B, cortical neurons infected by SARS-CoV-2 (in brown) and, in C, absence of infection in the same brain region of mice vaccinated with MVA-CoV2-S. (Images: IBiS)

“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 the immunogenicity and efficacy of the vaccine against different variants of SARS-CoV-2, support the conduct of phase I clinical trials with said vaccine or similar prototypes to assess their safety and immunogenicity”, the authors of the study emphasize.

The study is titled “Full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice conferred by MVA-CoV2-S vaccine candidate”. And it has been published in the academic journal Nature Neuroscience. (Source: IBiS / University of Seville)