Spanish researchers have tested a newly developed vaccine that prevents COVID infections from impacting patient’s neurological function.
Using a mouse model susceptible to COVID, the multidisciplinary team of Spanish researchers, including groups from the University of Seville and the Spanish National Research Council (CNB-CSIC), demonstrated the ability of SARS-CoV-2 to infect different regions of the brain and cause brain damage, as well as the CNB-CSIC vaccine’s capacity to fully protect against such infection.
One or two doses of the 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, and this protection was maintained even after reinfection.
Lead author Dr Javier Villadiego, from the Department of Medical Physiology and Biophysics at the University of Seville, explained that past research studied the evolution of viral infection in different brain regions, noting that viral replication occurs in neurons, producing neuropathological alterations such as neuronal loss, glial activation, and vascular damage.
“Even though the virus’ main impacts are on the respiratory system, many of those infected also displayed neurological symptoms such as anosmia, headaches, malaise, cognitive loss, epilepsy, ataxia, and encephalopathy,” Dr Villadiego said.
“However, COVID’s impact on the on the nervous system has not been characterized in detail and it was unknown if the vaccines developed against COVID prevent the spread of SARS-CoV-2 to the central nervous system and confer protection against brain injury.
“We have carried out a very detailed anatomic-pathological and molecular study of the brain regions and the types of cells that have been infected by the virus and it is remarkable how the virus infects different areas.
“An important observation, revealed by the histological analyses of brains from SARS-CoV-2-infected mice, was that most of the infected cells show a neuronal morphology, suggesting that viral replication occurs primarily in neurons. This was confirmed by high-resolution confocal microscopy analysis.”
Direct infection of the central nervous system (CNS) was supported by the detection of SARS-CoV-2 in both the cerebrospinal fluid of patients with COVID and in a considerable proportion of brain autopsies conducted on patients who died from the disease.
“Furthermore, SARS-CoV-2 has also been detected in the brain of different experimental animal models, including transgenic and knock-in mice expressing the human angiotensin-converting enzyme 2 (hACE2), as well as natural hosts of SARS-CoV-2 such as hamsters, ferrets and nonhuman primates,” Dr Villadiego said.
“Additionally, biomarkers of cerebral injury have also been found to be elevated in patients with mild or moderate infection, and neurological manifestations are common in patients recovered from the acute phase of COVID, suggesting the possibility of chronic brain impairment associated with long-COVID.”
The study indicated that SARS-CoV-2 brain replication began between two and four days after inoculation with SARS-CoV-2, with the highest levels of infection seen in ventral areas of the brain, such as the hypothalamus, amygdala, and basal forebrain.
Between four and six days, viral replication spread to most cerebral regions, producing a severe SARS-CoV-2 infection.
Once the pattern of infection in the brain by SARS-CoV-2 was established, the researchers evaluated the efficacy of the Spanish vaccine candidate MVA-CoV2-S, developed by Mariano Esteban and Juan García Arriaza, fellow researchers from the CNB-CSIC.
The vaccine successfully completed three different animal trials early last year and co-author Dr Juan García-Arriaza, from the Department of Molecular and Cellular Biology at the CNB-CSIC, explained that in this study, the team immunized mice with either one or two doses of MVA-CoV2-S before analysing its capability to protect against infection and damage to the brain.
“And 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 it prevents associated brain damage, even after a reinfection with the virus,” Dr García-Arriaza said.
“This demonstrates the great efficacy and immunogenic power of the vaccine that induces sterilizing immunity in the brain and these results reinforce previous data on the immunogenicity and efficacy of the MVA-CoV2-S vaccine in various animal models.”
Furthermore, analysis of brain blood vessels showed that mice vaccinated with MVA were also protected against the appearance of abnormal brain blood vessels after being infected by COVID, and the results suggested that the systemic response induced by MVA-S vaccination activated brain-resident immune cells – reinforcing the idea of active communication between the peripheral and central compartments of the immune system.
“The data we have obtained on SARS-CoV-2 infection in the brain are compatible with the neurological pathology observed in patients with COVID,” the authors concluded.
“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 observed in several people infected with SARS-CoV-2.”