Development of a Tick-Borne Encephalitis Virus Nanoparticle Vaccine Utilizing Envelope Dimer

ABSTRACT Tick-borne encephalitis virus (TBEV) is primarily transmitted to humans through tick bites, leading to symptoms of encephalitis with a fatality rate ranging from 1% to 30%, depending on the virus subtype. Currently, only inactivated virus vaccines are available for human use, though break-through infections can still occur. Therefore, developing new vaccines against TBEV is crucial. In this study, we designed and characterized a novel nanoparticle-based TBEV envelope (E) dimer vaccine. We successfully expressed and purified the TBEV E dimer by engineering disulfide bond mutants, and animal experiments demonstrated that the E dimer protein elicited a stronger immunogenic responses compared to the E monomer protein. Further, antibody depletion experiment confirmed that the E dimer protein effectively mimics the virion surface structure, inducing robust humoral immunity targeted at neutralizing epitopes. We also presented the TBEV E dimer on the surface of the nanoparticle Mi3 using the SpyCatcher-SpyTag system, with animal experiment showing that this TBEV E dimer nanoparticle vaccine elicited a potent humoral immune response. These findings offer new insights into the immunogenicity of the TBEV E dimer and suggest that the nanoparticle-based TBEV E dimer vaccine represents a promising and highly effective candidate for TBEV immunization.