mRNA Vaccines: Design Principles, Mechanisms, and Manufacturing—Insights From COVID-19 as a Model for Combating Infectious Diseases

The full approval of two SARS-CoV-2 mRNA vaccines, Comirnaty and Spikevax, has greatly accelerated the development of numerous mRNA vaccine candidates targeting infectious diseases and cancer. mRNA vaccines provide a rapid, safe, and versatile manufacturing process while eliciting strong humoral and cellular immune responses, making them particularly beneficial for addressing emerging pandemics. Recent advancements in modified nucleotides and lipid nanoparticle delivery systems have further emphasized the potential of this vaccine platform. Despite these transformative opportunities, significant improvements are needed to enhance vaccine efficacy, stability, and immunogenicity.

This review outlines the fundamentals of mRNA vaccine design, the manufacturing process, and administration strategies, along with various optimization approaches. It also offers a comprehensive overview of the mRNA vaccine candidates developed since the onset of the COVID-19 pandemic, the challenges posed by emerging SARS-CoV-2 variants, and current strategies to address these variants. Finally, we discuss the potential of broad-spectrum and combined mRNA vaccines and examine the challenges and future prospects of the mRNA vaccine platform.