The application provides a PDCoV
virus mRNA vaccine which can be self-cleaved and expresses multiple
virus structure proteins and a preparation method thereof, the vaccine comprises mRNA for expressing PDCoV
virus S, M and N proteins, and LNP for encapsulating the mRNA, denoted as SMN-mRNA-LNP. The application firstly proposes a PDCoV mRNA vaccine strategy based on S, M and N combination, connects three structure proteins of PDCoV S, M and N by using a self-cleaving
peptide P2A, mutates the S
protein with double
proline, enables a single mRNA to express multiple PDCoV antigens, and utilizes the
neutralizing antibody induction ability of the S
protein, the
immune regulation function of the M
protein and the
cell immune activation characteristics of the N protein to construct a multi-level defense
system. Through evaluation of
immunogenicity,
antibody level and challenge protection effect of the vaccine in mice, suckling piglets and pregnant sows, a new idea for developing a broad-spectrum and high-efficiency PDCoV vaccine is provided, and practical basis for research and development of a
coronavirus multi-
antigen mRNA vaccine is provided.