Stability-centric Development of mRNA Vaccines: A Comprehensive Review of Design, Delivery, and Regulatory Considerations

INTRODUCTION: Messenger RNA (mRNA) vaccine technology has recently emerged as a revolutionary platform in modern immunology and vaccinology. Unlike conventional vaccines that rely on attenuated pathogens or protein subunits, mRNA vaccines deliver genetic instructions to host cells to produce antigenic proteins that trigger robust immune responses. The widespread success during the COVID-19 pandemic accelerated global interest in this platform. However, challenges such as mRNA instability, degradation by extracellular RNases, and delivery barriers still limit its broader application in other therapeutic areas. This review provides an in-depth analysis of current advancements in mRNA vaccine development, focusing on mRNA structure stabilization, innovative carrier systems, immunogenicity modulation, and potential clinical applications beyond infectious diseases. It also compares mRNA vaccines to traditional vaccine platforms and highlights their advantages and future prospects. METHODS: A comprehensive literature survey was conducted using databases such as PubMed, Google Scholar, ScienceDirect, and Web of Science with keywords "mRNA vaccine", "lipid nanoparticles", "delivery systems", "immunogenicity", "cancer vaccines", "stability enhancement techniques", and "COVID-19". Research articles, clinical trial reports, patents, and review papers published between 2000 and 2025 were screened. Out of more than 300 publications, 126 relevant articles were selected based on novelty, scientific contribution, and relevance to vaccine development and delivery. The gathered information was critically organized and summarized. RESULT: The review highlights formulation strategies such as nucleoside-modified mRNA, selfamplifying mRNA, and circular mRNA to enhance stability and translation efficiency. Delivery vectors including lipid nanoparticles (LNPs), polymeric nanoparticles, and lipid-polymer hybrids are discussed, emphasizing their role in protecting mRNA from degradation and enabling targeted delivery. In addition to infectious diseases, the use of mRNA vaccines for cancer immunotherapy and personalized medicine is examined. Clinical findings confirm high efficacy and potent immune responses, although reactogenicity and cold-chain dependence remain major limitations. DISCUSSION: This review offers a comprehensive overview of mRNA vaccine development and highlights key scientific innovations addressing the inherent challenges of mRNA instability and delivery. By comparing current delivery strategies and formulation methods, it provides valuable insights for researchers designing next-generation mRNA vaccines with improved safety, efficacy, and broader applicability. CONCLUSION: mRNA vaccines represent a transformative approach in vaccine science, with tremendous potential for rapid adaptation against emerging pathogens and personalized treatment strategies. Ongoing research aimed at improving thermostability, reducing adverse immune responses, and expanding disease coverage may further strengthen global acceptance of mRNA technology. Continued advances in delivery systems and regulatory approval frameworks will be essential for expanding its application across therapeutic domains.