The invention relates to the technical field of vaccine preparation, and discloses a method for preparing a BVDV-1 vaccine by a non-cap-dependent mRNA (
messenger ribonucleic acid) technology, which is characterized in that an IRES sequence of CVB3 is inserted into the upstream of a BVDV-1E2
gene to replace a 5'end cap structure of the traditional mRNA, so that the production process is obviously simplified, the dependence on expensive enzymatic reaction is reduced, the
vaccine production cost is reduced, and the production efficiency is improved. The method is especially suitable for large-scale economic sensitive scenes such as
animal husbandry. According to the present invention, the non-capped mRNA is encapsulated by using the lipid
nanoparticle (LNP) with the specific
molar ratio, such that the stability of the mRNA and the target
cell delivery efficiency are effectively improved, the
immunogenicity limitation caused by insufficient translation efficiency of the non-capped mRNA is overcome, and the immune response equivalent to the commercial vaccine is achieved in the
large animal. The safety
advantage is particularly prominent,
inflammatory response or abnormal hemogram is not observed in all animal models, a novel solution with high efficiency, safety and economical efficiency is provided for prevention and control of
livestock epidemic diseases, and the method is particularly suitable for animal infectious diseases such as bovine
viral diarrhea needing long-term and extensive immunization.