Study Shows mRNA Vaccine Revitalizes the Immune System

Researchers from the German Cancer Research Center (DKFZ), the HI-STEM* institute and the Broad Institute have demonstrated that weakened immune systems of older individuals can be rejuvenated using mRNA technology to transform the liver in mice into a temporary source of immune regulatory factors that are naturally lost during aging. This restores the formation of new immune cells, allowing older animals to develop robust immune responses again and fight tumors effectively.

In the study, the researchers specifically showed that the liver can be transiently repurposed to restore age-diminished immune cues and improve T cell function in aged mice. These immune cues were found by performing multi-omic mapping across central and peripheral niches in young and aged animals, leading to the identification of Notch and Fms-like tyrosine kinase 3 ligand (FLT3L) pathways, together with interleukin-7 (IL-7) signalling, as declining with age. Delivery of mRNAs encoding Delta-like ligand 1 (DLL1), FLT3L and IL-7 to hepatocytes expanded common lymphoid progenitors, boosted de novo thymopoiesis without affecting haematopoietic stem cell (HSC) composition, and replenished T cells while enhancing dendritic cell abundance and function. 

Results shows that treatment with these mRNAs improved peptide vaccine responses and restored antitumor immunity in aged mice by increasing tumor-specific CD8+ infiltration and clonal diversity and synergizing with immune checkpoint blockade. These effects were reversible after dosing ceased and did not breach self-tolerance, in contrast to the inflammatory and autoimmune liabilities of recombinant cytokine treatments.

According to the researchers, these findings underscore the promise of mRNA-based strategies for systemic immune modulation and highlight the potential of interventions aimed at preserving immune resilience in aging populations.