Advancing mRNA vaccines for infectious diseases: key components, innovations, and clinical progress

Vaccination remains a cornerstone in preventing infectious diseases and managing outbreaks. The COVID-19 pandemic has underscored the revolutionary impact of mRNA vaccine technology, which utilizes pathogenderived genomic sequences to generate specific antigens. This process involves in vitro transcription of mRNA, encoding target antigens that are subsequently encapsulated within lipid nanoparticles (LNPs) for efficient delivery into host cells. Once internalized, the mRNA enables antigen expression, triggering a robust immune response. This platform dramatically accelerates vaccine development timelines and offers unparalleled adaptability, making mRNA vaccines particularly advantageous in addressing emerging infectious diseases. The clinical success of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) has fueled broader applications, including influenza, respiratory syncytial virus (RSV), Zika, and HIV. Notably, mRNA-1345 became the first FDA-approved RSV mRNA vaccine, while self-amplifying RNA and multivalent vaccines are advancing in trials. However, CureVac's CVnCoV failed due to lack of nucleoside modifications, and mRNA-1325 (Zika) showed poor immunogenicity. Additionally, mRNA-1365 (RSV) faced an FDA clinical hold due to safety concerns. These cases highlight the need for continued optimization in sequence design, delivery, and safety assessment. Despite advancements, a key hurdle persists, including mRNA instability, ultra-low storage requirements, and LNP liver accumulation. Innovations such as lyophilization and selective organ targeting technology are being explored to improve stability extrahepatic delivery. This review examines mRNA vaccine optimization strategies, clinical progress, and challenges, providing insights into future developments in this evolving field.