Respiratory virus mRNA vaccines: mRNA Design, clinical studies, and future challenges

Respiratory infectious diseases frequently erupt on a global scale, with RNA viruses, such as SARS-CoV-2, RSV, and influenza viruses, posing challenges to vaccine development due to their high mutation rates. Traditional vaccine development cycles are lengthy and struggle to keep pace with rapidly evolving viruses, whereas messenger RNA (mRNA) vaccines have demonstrated significant advantages due to their short development periods, straightforward production, and low costs. After the outbreak of the COVID-19 pandemic, multiple mRNA vaccines, including Pfizer-BioNTech and Moderna, rapidly received emergency use authorization, validating their feasibility. The Nobel Prize in Physiology or Medicine in 2023 was awarded to Katalin Karikó and Drew Weissman, underscoring the efficacy of mRNA vaccine technology. In 2024, the U.S. Food and Drug Administration (FDA) approval of Moderna's respiratory syncytial virus (RSV) mRNA vaccine marked the immense potential of mRNA technology in vaccine innovation. This review article summarizes the design, clinical research, and future challenges of mRNA vaccines for respiratory viruses, delving into antigen design, mRNA delivery systems, and advancements in vaccines for multiple respiratory viruses, including innovations in self-amplifying mRNA and circular mRNA vaccines. Additionally, the development of combination vaccines is underway, aiming to provide protection against multiple viruses through a single administration. Despite the significant progress in mRNA vaccine development, challenges remain regarding raw material costs, stability, and delivery efficiency. In the future, with technological advancements and the accumulation of clinical experience, the design strategies and delivery systems of mRNA vaccines are expected to be continuously optimized, thereby enhancing their safety and efficacy.