Title Effects of exogenous SARS-CoV-2 S1 protein and mRNA vaccines on mixed neuronal–glial cell cultures
Authors Markevičius, Vytenis ; Dirvelytė-Valauskė, Eimina ; Neniškytė, Urtė ; Borutaitė, Vilmantė
DOI 10.3390/medicina62010198
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Is Part of Medicina.. Basel : MDPI. 2026, vol. 62, iss. 1, art. no. 198, p. [1-18].. ISSN 1010-660X. eISSN 1648-9144
Keywords [eng] glial cells ; inflammatory cytokines ; microglia ; mRNA vaccines ; neuroinflammation ; neurons ; SARS-CoV-2
Abstract [eng] Background and Objectives: SARS-CoV-2 produces potentially pathogenic molecules, such as single-stranded RNA and spike proteins, which can potentially activate microglial cells. In this study, we aimed to investigate whether SARS-CoV-2 spike protein S1 and mRNA vaccines can cause neurotoxicity directly or through microglial involvement. Materials and Methods: Primary cerebellar granule cell cultures isolated from Wistar rats and organotypic hippocampal slice cultures from transgenic C57BL/6J mice were used in the experiments. Imaging and quantitative analysis of cell viability, proliferation, and phagocytic activity were performed using light and fluorescence microscopy. Results: The exogenous SARS-CoV-2 S1 protein at 50 µg/mL concentration induced neuronal cell death in neuronal–glial co-cultures and stimulated microglial proliferation during the first 3 days of exposure without an effect on inflammatory cytokine secretion. Single application of Tozinameran/Riltozinameran and Original/Omicron BA. 4–5 vaccines did not affect neuronal viability and total neuronal number in cell co-cultures after 7 days of exposure. In contrast, three repeated treatments with mRNA vaccines at 6 ng/mL caused microglial proliferation without affecting microglial phagocytosis and TNF-α release. In organotypic brain slice cultures, only Tozinameran/Riltozinameran stimulated microglial cell proliferation in female brain slices, while male brain slices remained unaffected by both vaccines, indicating sex-dependent effects. Conclusions: The findings suggest that mRNA vaccines do not exert neurotoxic effects in primary neuronal–glial co-cultures, but induce microglial proliferation, particularly in female brains in the absence of inflammatory cytokine release. SARS-CoV-2 S1 protein at high concentrations directly induces neuronal death.
Published Basel : MDPI
Type Journal article
Language English
Publication date 2026
CC license CC license description