Abstract: The emergence of mRNA vaccine technology has revolutionized vaccine development, as demonstrated during the COVID-19 pandemic. With epitope-based design approaches, mRNA vaccines offer unprecedented potential for developing targeted immunotherapies against various pathogens.
This review examines the status of epitope- based mRNA vaccine development, providing a comprehensive analysis of computational and experimental methodologies for epitope identification, structural considerations for optimal design, and delivery technologies.
We critically evaluate the performance of current prediction tools and validation approaches while presenting diverse case studies of epitope-based vaccines in various stages of development across viral, bacterial, and parasitic pathogens and cancer applications.
These examples span from pre- clinical studies to FDA-approved products, such as Moderna’s RSV mRNA-1345 (NCT05127434) and personalized neoantigen cancer vaccines, with detailed analysis of epitope selection strategies, structural arrangements, and clinical data. While significant progress has been made, challenges in epitope prediction accuracy, optimal epitope arrangement, and translation of in silico predictions to in vivo efficacy remain.
We also dis- cuss the regulatory landscape for these novel vaccine constructs and emerging ap- proaches, including multi-pathogen epitope mosaics, AI-driven design, and real-world evidence integration, pointing toward a new era of rational vaccine development against infectious diseases and cancer.
