Engineered VP1 mRNA Vaccine Induces Immunity and Complete Protection Against Feline Calicivirus in Cats

Feline calicivirus (FCV) is a major pathogen of upper respiratory tract diseases in cats, posing a significant threat to feline health. While current FCV preventive measures rely primarily on traditional vaccines, messenger RNA (mRNA) vaccines have emerged as a promising alternative, offering high efficacy, safety, rapid clinical development, and potential for fast, cost‐efficient production. In this study, we designed a modified nucleotide sequence with a 124‐amino acid deletion at a position in the region of the FCV‐VP1 protein as an immunogen. The plasmid encoding the codon‐optimized VP1 sequence was constructed, and VP1‐mRNA was generated by in vitro transcription (IVT) and capping. After transfection into BHK‐21 cells, immunofluorescence assay (IFA) and WB confirmed successful FCV‐VP1 expression. Subsequently, the mRNA was encapsulated into lipid nanoparticles (LNPs) to prepare the LNP‐VP1‐mRNA vaccine. Characterization analysis revealed a uniform particle size distribution (polydispersity index PDI = 0.169) and a stable surface charge (zeta potential = −1.67 mV). A prime‐boost immunization strategy was employed, which involved two intramuscular injections to immunize BALB/c mice or cats with the LNP‐VP1‐mRNA vaccine. ELISA analysis demonstrated that the vaccine elicited elevated levels of anti‐FCV IgG and neutralizing antibodies in a dose‐dependent manner, accompanied by the secretion of cytokines including IFN‐β, IFN‐γ, IL‐4, and IL‐6. Importantly, the VP1 mRNA vaccine provided complete protection against FCV challenge in cats, without the typical clinical signs and with a 100% survival rate. Our results indicate that the LNP‐VP1‐mRNA vaccine is a promising candidate for combating FCV infection.