This invention relates to a fusion
antigen mRNA molecule, which encodes a
protein comprising at least two of the following:
hepatitis B surface
antigen protein sHBsAg,
hepatitis B core
antigen protein Core,
hepatitis B X antigen protein HBxAg, and
hepatitis B preS1 antigen protein PreS1, preferably comprising
hepatitis B surface antigen protein sHBsAg,
hepatitis B core antigen protein, and hepatitis B PreS1 antigen protein, denoted as sHBsAg-Core-PreS1, and its
amino acid sequence is shown in SEQ ID No. 17; the above-mentioned fusion antigen mRNA molecule can be prepared into an mRNA-LNP vaccine composition and used to treat
chronic hepatitis B
virus infection. The preferred sHBsAg-Core-PreS1 mRNA-LNP of this invention can normally express and present each encoded
target antigen in vivo, and achieve cross-presentation, cross-activation and enhanced expression, inducing
target antigen-specific humoral and cellular immune responses. It can also effectively overcome
immune tolerance in a mouse model of
chronic hepatitis B, and has excellent antiviral and immunotherapeutic effects. Compared with existing related therapeutic HBV mRNA-LNP vaccines, it effectively improves the
immune tolerance breakthrough threshold, providing a candidate vaccine and a new
immunotherapy strategy for the
immunotherapy of patients with chronic HBV infection.