Next-Generation mRNA Vaccines: Immunological Mechanisms and Challenges in Broad-Spectrum Viral Protection
Keywords:
mRNA vaccine, Broad-spectrum immunity, Viral variants, Antigen presentation, Self-amplifying mRNA (saRNA), Lipid nanoparticles (LNPs), Innate immunity, T cell response, B cell memory, Vaccine durability, Pandemic preparedness, Viral escape mechanismsAbstract
The mRNA vaccine platform has dramatically changed the domain of vaccinology by providing unparalleled speed, flexibility, and scale to respond to viral outbreaks. First generation mRNA vaccines were efficacious against SARS-CoV-2, however, next generation mRNA vaccines seek to confer broad spectrum protection against multiple,if not all, virus families, variants and zoonotic threats. In this study, the principles of mRNA vaccine−induced immunology are explored, including antigen presentation, innate immune activation, and B and T cell responses orchestration. In addition, it discusses important challenges encountered in antigenic variability, delivery system optimization, immunodominance, and durability of immune memory. Potential enhancements by means of improvements in self amplifying mRNA, thermostable formulations, and multivalent vaccine design are evaluated for enhancement of cross protection and global distribution. In this paper, we integrate recent preclinical and clinical data in a comprehensive overview of the next frontier in mRNA vaccine research and its ramifications for pandemic preparedness and universal vaccine strategies.
