The application discloses a vaccine heat-resistant protective agent, a preparation method and application thereof, and belongs to the technical field of vaccines. The vaccine heat-resistant protective agent comprises the following raw materials: polycarboxybetaine,
taurine, a
sugar substance, polysarcosine,
erythritol,
gelatin enzymatic
hydrolysate, a
metal ion chelating agent and a buffer. The application also provides a preparation method. Compared with the prior art, the synergistic effect of polycarboxybetaine,
taurine, a
sugar substance, polysarcosine,
gelatin enzymatic
hydrolysate,
erythritol and EDTA-Na2 can significantly improve the freeze-dried cake forming and reconstitution performance, shorten the reconstitution time, reduce the
turbidity and insoluble particles. After 2-8 DEG C, 25 DEG C and 37 DEG C storage and multiple freeze-thaw cycle investigations, the
antigen content residual rate and
glass transition temperature are obviously superior to those of a traditional
sucrose and
mannitol system, and the inactivation risk caused by
cold chain fluctuation can be effectively buffered.