Blood transcriptome profiling reveals distinct gene networks induced by mRNA vaccination against COVID-19

Messenger RNA (mRNA) vaccines represent a new class of vaccines that has been shown to be highly effective during the COVID-19 pandemic and that holds great potential for other preventative and therapeutic applications. Understanding the underlying mechanisms of the immune responses induced by this novel vaccine type and their relation to vaccine responses might help to further refine and optimize future vaccine design. In this study, we conducted an in-depth analysis of the blood transcriptome before and 24h after second and third vaccination with licensed mRNA vaccines against COVID-19 in humans, following a prime vaccination with either mRNA or ChAdOx vaccines. Utilizing an unsupervised weighted gene correlation network analysis, we identified distinct gene networks of co-varying genes characterized by either an expressional up- or down-regulation in response to vaccination. Down-regulated networks were associated with cell metabolic processes and regulation of transcription factors, while up-regulated networks were associated with myeloid differentiation, antigen presentation, and antiviral, interferon-driven pathways. Within this interferon-associated network, we identified highly connected hub genes such as STAT2 and RIGI, potentially playing important regulatory roles in the vaccine-induced immune response. The expression profile of this network significantly correlated with S1-specific IgG levels at the follow-up visit in vaccinated individuals. Those findings could be corroborated in an independent cohort of mRNA vaccine recipients. Collectively, insights from this study might contribute to current research endeavors aimed at further enhancing/ or optimizing vaccine-induced immunity. We collected whole blood for RNA-seq from 15 and 10 vaccine recipients both before (Pre) and 24 hours (24h) after the second (V2) and third (V3) COVID-19 vaccinations, respectively. All included participants received two mRNA booster vaccinations, following primary vaccination with either ChAdOx or an mRNA vaccine (see metadata). Seven participants were sampled both at V2 and V3. We compared the transciptional profile 24h after vaccination with the pre-vaccination profile at both vaccinations to analyze vaccine-induced changes in the transcriptome.