The invention provides a novel
adjuvant subunit rabies virus vaccine as well as a preparation method and application thereof, the vaccine takes a
rabies virus (RABV)
glycoprotein extracellular domain prepared by a
gene recombination technology as an
antigen, and takes a combination of
CpG oligodeoxynucleotide and QS21 as an
adjuvant. A contrast experiment is carried out on the vaccine, an LNP-mRNA-G-H270P vaccine, a commercial
inactivated vaccine and an aluminum
adjuvant subunit vaccine, and the result shows that the vaccine can induce a remarkably higher RABV-G
specific IgG antibody and
virus neutralizing antibody titer, and the humoral immune response is superior to that of other vaccines; meanwhile, moderate and effective Th1 type
cell immune response can be induced, so that
protective immunity can be supported; 100% protection is achieved in a lethal RABV
attack experiment, and the protection effect is equivalent to that of an mRNA vaccine and is remarkably superior to that of an aluminum adjuvant vaccine and a commercial
inactivated vaccine. The vaccine provided by the invention has a controllable
immune activation mechanism and relatively high safety, avoids the storage risk and excessive
inflammatory response of a
nucleic acid technology, and is a more reliable and universal choice in the current vaccine technology.