The FMDV P12A3C-UTR8 mRNA vaccine elicited robust immune responses and provided 100% protection against FMDV challenge in guinea pigs, comparable to a commercial inactivated vaccine.
Does UTR optimization (specifically UTR8) enhance antigen expression and immunogenicity of the FMDV P12A3C mRNA vaccine in preclinical models?
Optimization of untranslated regions, specifically UTR8, significantly enhances the translation efficiency and immunogenicity of the FMDV P12A3C mRNA vaccine in preclinical models.
Absolute Event Rate: 100% vs 0%
Foot-and-Mouth Disease (FMD) causes substantial economic losses to the global livestock industry annually. Current vaccines inadequately prevent infection and transmission of Foot-and-Mouth Disease Virus (FMDV), highlighting the urgent need for FMDV mRNA vaccines with enhanced immunogenicity and safety. The immunogenicity of mRNA vaccines is largely determined by sequence design, particularly the optimization of untranslated regions (UTRs), which significantly enhance mRNA stability and promote efficient antigen expression. In this study, eight UTR sequences were designed and evaluated using the enhanced green fluorescent protein (EGFP) reporter gene. Results showed that EGFP-UTR3 and EGFP-UTR8 performed best in protein expression. Subsequent integration of UTR3 and UTR8 into FMDV P12A3C mRNA revealed that P12A3C-UTR8 consistently achieved higher antigen expression across multiple cell models, elicited robust humoral and cellular immune responses in mice, and provided protection comparable to conventional inactivated vaccines in guinea pigs, indicating that UTR8 is a highly promising regulatory element for vaccine applications. Sequence analysis revealed that beyond the previously reported influence of the 5' UTR secondary structure, the GC content of the 3' UTR is strongly associated with mRNA translation efficiency. These findings elucidate the intrinsic link between UTR structure and function and provide critical theoretical support for optimizing FMDV mRNA vaccine and advancing novel vaccine development.
liu et al. (Sun,) conducted a other in Foot-and-Mouth Disease (FMD) (n=35). P12A3C-UTR8 mRNA vaccine vs. P12A3C-UTR3 mRNA vaccine, PBS, or inactivated FMDV vaccine was evaluated on Protection rate against FMDV challenge in guinea pigs. The FMDV P12A3C-UTR8 mRNA vaccine elicited robust immune responses and provided 100% protection against FMDV challenge in guinea pigs, comparable to a commercial inactivated vaccine.