Background: Since their emergency authorization in 2020, mRNA vaccines transformed global vaccinology demonstrating remarkable speed, flexibility, and efficacy, particularly in the COVID-19 response. These successes have catalyzed exploration of broader applications of mRNA platforms beyond SARS-CoV-2.
mRNA vaccine technology matured rapidly during the COVID-19 pandemic, demonstrating speed, scalability, and robust protective efficacy. Beyond SARS?CoV?2, the platform is expanding into prophylactic vaccines for respiratory and endemic pathogens, difficult viral targets (e.g., CMV, HIV), complex bacterial threats (e.g., M. tuberculosis), parasitic diseases (e.g., malaria), and therapeutic applications in oncology, allergy, and autoimmunity. Key advances include self?amplifying and trans?amplifying mRNA, circular RNA, improved untranslated regions (UTRs), next?generation lipid nanoparticles and polymeric carriers, thermo stabilization, alternative delivery routes (Intranasal, oral, micro needle patches), and AI?assisted antigen design. This narrative review synthesizes platform innovations, immunological mechanisms, manufacturing and regulatory considerations, safety and reactogenicity, equity and access, and outlines a roadmap for the next decade of mRNA vaccinology.