microRNAs (miRNAs) are small, non-coding RNA molecules that play crucial roles
in regulating gene expression. The 2024 Nobel Medicine Prize was awarded to Victor Ambros
and Gary Ruvkun for discovering them. However, there’s no microRNA-based drug on the market
yet. Can miRNAs be used for vaccine development? Here’s a summary of miRNA potential
functions from published papers for vaccine development.
1. Adjuvant development: Incorporation of miRNAs as adjuvants
into DNA vaccine constructs can ameliorate innate antiviral pathways which usually limit
maximal antigen expression.
In this article,
vaccinating BALB/c mice with a DNA vaccine vector delivering miRNA targeting PERK, but not
PKR, was able to augment HIV-1 envelope (Env) antigen-specific T cell immunity.
2. Immune response modulation: miRNAs can influence the innate
and adaptive
immune responses by regulating the expression of genes involved in these processes. This can
help in designing vaccines that elicit stronger and more targeted immune responses.
MicroRNA 155 (miR-155) deficiency in dendritic cells impairs their maturation,
migration, cytokine production, and ability to activate T cells. In this article, dendritic
cell vaccine overexpressing miR-155 exhibited enhanced functions in response to breast
cancer antigens.
3. Biomarker discovery: miRNAs can serve as biomarkers to
monitor the effectiveness of a vaccine. Changes in specific miRNA expression levels can
indicate how well a vaccine is working, allowing for more precise adjustments in vaccine
design and administration.
After COVID-19 vaccination, data in this article suggest a potential of
circulating extracellular vesicles (EV) miRNAs as biomarkers for vaccine efficacy and
adverse reactions. EV miR-92a-2-5p levels in sera were negatively correlated with degrees of
adverse reactions, and EV miR-148a levels were associated with specific antibody titers.