CNB-CSIC vaccine fully protects against SARS-CoV-2 infection in the brain

A recent study published in the journal Nature NeuroscienceSpanish researchers used a mouse model to study a modified vaccinia virus Ankara (MVA) vector in protecting against SARS-CoV-2 infection in the brain, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ) described the efficacy of the vaccine candidate.

study: Complete protection from SARS-CoV-2 brain infection and injury in susceptible transgenic mice conferred by the MVA-CoV2-S vaccine candidateImage Credit: DOERS / Shutterstock

Background

Although coronavirus disease 2019 (COVID-19) is primarily associated with respiratory symptoms, neurological symptoms such as cognitive impairment, olfactory disturbances, aging, vertigo, encephalopathy, and ataxia have also been observed in many patients. Cerebrospinal fluid samples from COVID-19 patients and brain autopsies of patients who died from this disease have revealed the presence of SARS-CoV-2, indicating direct infection of the central nervous system (CNS). Additionally, studies in animal models such as ferrets, hamsters, and non-human primates have detected SARS-CoV-2 in the brain. Severe COVID-19 is associated with elevated biomarkers of neurovascular pathology, neuronal damage, and brain injury.

The COVID-19 vaccines currently in use have been successful in reducing the severity of SARS-CoV-2 infection and hospitalization requirements, but have prevented the spread of SARS-CoV-2 to the central nervous system and the brain. Its effectiveness in protecting against infection is unknown. Considering the number of neurological complications that COVID-19 patients experience during infection and after recovery in cases of prolonged COVID, it is imperative to explore vaccines that can protect against SARS-CoV-2 brain infection. Essential.

About research

In the current study, researchers investigated: efficacy of MVA vector vaccine expressing SARS-CoV-2 spike protein (MVA-CoV2-S) has been shown to induce spike protein-specific long-term humoral and memory T-cell responses in previous studies by the same team of researchers using mouse, hamster and rhesus monkey models, reducing morbidity, Protected from pathology.mortality, and cytokine stormUsing keratin 18-human angiotensin-converting enzyme-2 (K18-hACE2) mice susceptible to SARS-CoV-2 infection, we investigated viral spatiotemporal spread, neuronal cell death, and associated disease in key regions of the brain. I studied physical changes.

To initially characterize SARS-CoV-2 infection in the brain, K18-hACE2 mice were inoculated intranasally with SARS-CoV-2 and analyzed immunohistochemistry for nucleocapsid proteins 2, 4, and 6 days after infection. Did. Additionally, neuronal density in the hypothalamus, hippocampus, and cortex was quantified to understand whether severe SARS-CoV-2 infection causes neuronal cell death.

After the neuropathology and spatiotemporal spread of SARS-CoV-2 in the brain of K18-hACE2 mice were characterized, the efficacy of MVA-CoV2-S in protecting against SARS-CoV-2 infection and neuronal injury in the brain was demonstrated. Rated. A K18-hACE2 mouse was immunized intramuscularly with one or two doses of her MVA-CoV2-S vaccine at 28-day intervals. at 63^rd On the same day, mice were intranasally challenged with SARS-CoV-2. Positive controls consisted of her K18-hACE2 mice inoculated her twice with wild-type empty her MVA vector and challenged with SARS-CoV-2. Four days after infection, he euthanized the mice and removed and processed the brains.

Additionally, a second study involving MVA-CoV2-S vaccinated mice that survived SARS-CoV-2 infection was conducted to determine vaccine efficacy in protecting against SARS-CoV-2 reinfection. . Six days after his second SARS-CoV-2 challenge, he euthanized the mouse and removed the brain for pathological observation. Immunohistochemical analysis to detect SARS-CoV-2 nucleocapsid protein in different regions of the brain was performed during both experiments to confirm SARS-CoV-2 brain infection.

result

The results showed that SARS-CoV-2 replication in the brain caused neuronal cell loss, vascular damage, and glial activation in K18-hACE2 mice. However, one or two doses of MVA-CoV2-S vaccine completely prevented SARS-CoV-2 infection in the brain during the initial stages of infection and reinfection. Vaccine-induced immunity successfully prevented viral replication and neuronal damage in all regions of the brain.

Histological analyzes used to characterize SARS-CoV-2 infection in the brain revealed that the amygdala, hypothalamus, and basal forebrain were the first regions to be infected. The olfactory bulb showed only mild SARS-CoV-2 infection at 4 days post-infection, with severe viral replication detectable only 6 days post-infection, by which time infection had spread to most areas of the brain. A significant level of neuronal cell death was also observed, suggesting that viral replication in the brain occurs primarily in neurons.

These results corroborated those of other studies in which the olfactory bulbs of patients who died days after SARS-CoV-2 infection did not show significant levels of SARS-CoV-2 replication. Given the fact that the hypothalamus, where viral replication was first detected at the highest levels, also has fenestrated blood-brain barrier capillaries, the hematologic route for SARS-CoV-2 entry into the CNS is , seems more likely than olfactory. root.

Conclusion

Overall, the results showed that the COVID-19 vaccine candidate MVA-CoV2-S showed promising efficacy against brain SARS-CoV-2 infection in mice. We confirmed that one or two doses of the vaccine protected SARS-CoV-2-infected mice from infection, replication, neurological damage during primary infection, and reinfection.