Synthetic messenger RNA vaccines and transcriptomic dysregulation: Evidence from new-onset adverse events and cancers post-vaccination

Abstract

BACKGROUND

Synthetic messenger RNA (mRNA) vaccines have raised concerns regarding prolonged spike protein expression, immune activation, and potential off-target effects.

AIM

To investigate transcriptomic alterations in individuals with new-onset adverse events or cancer following mRNA coronavirus disease 2019 vaccination.

METHODS

Bulk RNA sequencing was performed on peripheral blood from two patient groups: (1) Individuals with new-onset nonmalignant adverse events; and (2) Individuals newly diagnosed with cancer post-vaccination. A control group of normal individuals was used for comparison. Differential gene expression was analyzed using DESeq2, and Gene Set Enrichment Analysis was conducted using the MSigDB database and custom gene sets.

RESULTS

Both vaccine patient groups displayed widespread transcriptional dysregulation. In the nonmalignant adverse event group, hallmark enrichments included mitochondrial dysfunction, proteasome-mediated stress, transcriptomic instability, and systemic inflammation. The cancer group exhibited additional hallmarks of genomic instability and epigenetic reprogramming. Nonsense-mediated decay, ribosomal stress, and myelocytomatosis oncogene activation were prominent in both groups, while immune signaling via toll-like receptors and type I interferons was particularly elevated in cancer patients. The observed transcriptomic profiles indicate cellular stress responses, mitochondrial dysfunction, and immune dysregulation following exposure to mRNA vaccines, potentially in susceptible individuals.

CONCLUSION

Shared and distinct molecular signatures in both cohorts demonstrate underlying mechanisms contributing to post-vaccine symptomatology and complications, including oncogenesis and or progression of malignant disease. These findings underscore the need for a deeper investigation into the long-term safety of mRNA vaccines and host response variability.

Keywords: Coronavirus disease; Vaccine; RNA-seq; Immune dysregulation; Cancer

Core Tip: This study demonstrates that individuals experiencing new-onset adverse events or cancer after messenger RNA (mRNA) coronavirus disease 2019 vaccination exhibit widespread transcriptomic dysregulation. Bulk RNA sequencing revealed hallmarks of mitochondrial dysfunction, systemic inflammation, proteasome and ribosomal stress, and nonsense-mediated decay, with additional genomic instability and epigenetic reprogramming in cancer patients. Notably, myelocytomatosis oncogene activation and heightened immune signaling via toll-like receptors and type I interferons were observed. These findings highlight shared and distinct molecular signatures, underscoring the need for further investigation into long-term mRNA vaccine safety and host variability.