Virology journalJan 4, 2026

Improving untranslated regions increases protein production and immune response of the FMDV P12A3C mRNA vaccine

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Updated Jan 5, 2026

Abstract

P12A3C-UTR8 achieved higher antigen expression in multiple cell models and elicited robust immune responses in mice.

Eight UTR sequences were designed and evaluated for their impact on mRNA stability and protein expression.
EGFP-UTR3 and EGFP-UTR8 showed the best performance in protein expression from the tested sequences.
Integration of UTR3 and UTR8 into FMDV P12A3C mRNA resulted in consistently higher antigen expression.
P12A3C-UTR8 elicited strong humoral and cellular immune responses in mice.
In guinea pigs, P12A3C-UTR8 provided protection comparable to traditional inactivated vaccines.
The GC content of the 3' UTR is strongly associated with mRNA translation efficiency.

Simplified

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.

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Improving untranslated regions increases protein production and immune response of the FMDV P12A3C mRNA vaccine

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