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

• Published in: European journal of immunology 2024-11, Vol.54 (11), p.e2451236-n/a
• Main Authors: Riemann, Lennart, Weskamm, Leonie M., Mayer, Leonie, Odak, Ivan, Hammerschmidt, Swantje, Sandrock, Inga, Friedrichsen, Michaela, Ravens, Inga, Fuss, Janina, Hansen, Gesine, Addo, Marylyn M., Förster, Reinhold
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antigen presentation; BNT162b2; Cell differentiation; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 vaccines; COVID-19 Vaccines - immunology; Down-regulation; Female; Gene expression; Gene Expression Profiling; Gene networks; Gene regulation; Gene Regulatory Networks; Genes; Humans; Immune response; Immunoglobulin G; Interferon; Male; Middle Aged; mRNA Vaccines; RNA, Messenger - genetics; RNA, Messenger - immunology; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; Stat2 protein; Systems vaccinology; Therapeutic applications; Transcription factors; Transcriptome; Transcriptomes; Vaccination - methods; Vaccine response
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.202451236

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. While it is known that the transcriptional activity of various genes is altered following mRNA vaccination, identifying and studying gene networks could reveal important scientific insights that might inform future vaccine designs. In this study, we conducted an in‐depth weighted gene correlation network analysis of the blood transcriptome before and 24 h after the second and third vaccination with licensed mRNA vaccines against COVID‐19 in humans, following a prime vaccination with either mRNA or ChAdOx1 vaccines. Utilizing this unsupervised gene network analysis approach, we identified distinct modular networks of co‐varying genes characterized by either an expressional up‐ or downregulation in response to vaccination. Downregulated networks were associated with cell metabolic processes and regulation of transcription factors, while upregulated 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 and associated upstream transcription factors, 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 a second, independent cohort of mRNA vaccine recipients. Collectively, results from this modular gene network analysis enhance the understanding of mRNA vaccines from a systems immunology perspective. Influencing specific gene networks could lead to optimized vaccines that elicit augmented vaccine responses. Using an unsupervised weighted gene correlation analysis on blood transcriptomes pre‐ and post‐COVID‐19 mRNA vaccination, we identify distinct gene networks that are up‐ and downregulated in response to vaccination. A particular interferon‐associated network significantly correlated with induced antibody levels and was further characterized, for example, by identifying network hub genes.