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Research progress on immune mechanism and control strategy of dsRNA impurities in mRNA vaccine

Xinjun Liu1, Chaoying Hu1, Qian He1

  • 1State Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National institutes for Food and Drug Control, Beijing, China.

Expert Review of Vaccines
|May 22, 2025
PubMed
Abstract

Insights

Double-stranded RNA (dsRNA) is a critical impurity in mRNA vaccines that can trigger side effects. This review covers dsRNA generation, immunity activation, and challenges in detection and control for improved vaccine safety.

Area of Science:

  • Molecular Biology
  • Vaccinology
  • Immunology

Background:

  • Double-stranded RNA (dsRNA) is a significant impurity in mRNA vaccines produced via in vitro transcription (IVT).
  • dsRNA can activate innate immunity, potentially leading to adverse effects and impacting vaccine safety.
  • The presence and impact of dsRNA impurities are critical quality attributes (CQAs) for mRNA vaccines.

Purpose of the Study:

  • To summarize dsRNA generation mechanisms and immune activation pathways.
  • To analyze current challenges in dsRNA detection and control strategies.
  • To discuss regulatory standards for dsRNA impurities in mRNA vaccines.

Main Methods:

  • Literature review of dsRNA generation, immunomodulation, detection, and control.
  • Analysis of current challenges and regulatory landscapes.
  • Discussion of Quality by Design (QbD) approaches for mRNA production.

Main Results:

  • dsRNA generation is primarily linked to T7 RNA polymerase during IVT.
  • The structural heterogeneity and immunomodulatory mechanisms of dsRNA are not fully understood.
  • There is a lack of standardized detection methods and regulatory standards for dsRNA impurities.

Conclusions:

  • Standardized detection methods and quality standards for dsRNA are crucial for mRNA vaccine safety.
  • Implementing Quality by Design (QbD) can minimize dsRNA impurities during mRNA production.
  • Further research into dsRNA's immune stimulation mechanisms is needed to enhance mRNA vaccine platforms.
Keywords:
dsRNAimpurities controlinnate immunitymRNAmechanisms

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