SARS-CoV-2 mRNA-based vaccines in the Aicardi Goutières Syndrome

https://doi.org/10.1016/j.ymgme.2022.10.001Get rights and content

Abstract

Aicardi Goutières Syndrome (AGS) is an autoinflammatory disorder resulting in sustained interferon activation through defects in nucleic acid modification and sensing pathways. Thus, mRNA-based vaccination used against SARS-CoV-2, raise disease-specific safety concerns. To assess interferon signaling, we tested mRNA SARS-CoV-2 vaccines in AGS whole blood samples. Interferon activation is measured through quantitation of interferon signaling gene (ISG) expression and is increased in AGS patients. There was no increase in ISG scores from baseline following treatment with the nucleoside modified mRNA formulation compared to an increase with unmodified. A patient-family survey reported that the vaccines were well tolerated. These findings suggest that COVID vaccination using nucleoside-modified forms of mRNA vaccines are unlikely to directly stimulate ISG expression in response to mRNA internalization in AGS tissues. With continued community spread, we recommend vaccination using nucleoside-modified mRNA vaccines in this rare disease group in individuals for whom vaccines were previously well tolerated.

Keywords

COVID
Vaccination
mRNA
Aicardi Goutières syndrome

Abbreviations

COVID-19
coronavirus disease 2019
IFN
interferon
ISG
interferon stimulatory gene
AGS
Aicardi Goutières Syndrome
LNP
lipid nanoparticle

Data availability

Data will be made available on request.

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1

These authors contributed equally to the manuscript

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