Evaluating the Protective Immunity of 5'-Cap Altered Rabies mRNA Vaccines in a Mouse Model.

Introduction: Rabies Virus (RV or RABV) is a neurophilic pathogen predominantly transmitted to humans through bites, scratches, or wounds. Upon entering the central nervous system, the virus can cause severe symptoms, including acute encephalitis and paralysis, ultimately leading to death with an almost 100% mortality rate. Hence, it is essential to develop an effective oral rabies vaccine.

Methods: We designed and synthesized three modified 5'-cap mRNA vaccines (RV-01(CAP- 01), RV-01(CAP-02) and RV-01(CAP-03)) encoding rabies virus glycoproteins in vitro and evaluated their immunogenicity and protective effect in mice.

Results: The modified 5'-cap vaccine was successfully constructed and could be effectively expressed in HEK293 cells. The antibody detection results revealed the abundance of RABV-G in RV-01(CAP-01), RV-01(CAP-02) and RV-01(CAP-03). ELISPOT assays indicated that these variants promoted the production of immune-related cytokines. Furthermore, the modified 5'-cap vaccines could reduce the rabies viral load of mice and effectively prolong their survival.

Discussion: The rabies mRNA vaccine had high efficacy and safety in preventing rabies, suggesting the great potential of mRNA as a promising candidate for RABV vaccines. However, the potential causes of the differences in the performance of the three modified 5'-cap rabies mRNA vaccines and the clinical application of 5'-Cap altered rabies mRNA vaccines need to be explored.

Conclusion: Hence, these results demonstrated that the modified 5'-cap mRNA vaccine was effective in inducing immune responses, which might be considered a promising prophylactic strategy for rabies.