Comparison of candidate vaccines against Tick-borne encephalitis based on mRNA, simian adenovirus serotype 25 and a chimeric replication-competent yellow fever vaccine strain

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Abstract
Introduction. The spread of tick-borne encephalitis virus (Orthoflavivirus encephalitidis) continues. Existing vaccines have several limitations. Research new vaccine platforms will enable the development of more effective strategies of disease prevention. Materials and methods. The constructs for producing vaccine preparations were obtained using the methods described earlier. Study of the effectiveness of candidate vaccines based on chimeric yellow fever virus, adenovirus serotype 25 and mRNA encoding a fragment of the tick-borne encephalitis viral polyprotein corresponding to the PrM and E regions, immunogenicity and protective efficacy was performed using BALB/c mice. The neutralizing activity assessment of animal sera and mice challenge were performed using the tick-borne encephalitis virus strain Sofjin-Chumakov. Results. It was established that immunization of animals with mRNA encoding the PrM and E regions of the viral polyprotein of tick-borne encephalitis virus resulted in the induction of a higher level of neutralizing antibodies compared to the other vaccine platforms studied in the immunization schedule used. In addition, this platform provided 100% protection of animals from the lethal infection caused by the tick-borne encephalitis virus. Conclusion. The study demonstrated that delivery of the nucleotide sequence encoding the PrM and E regions of the tick-borne encephalitis virus polyprotein within mRNA elicits a pronounced humoral immune response during animal immunization. These results demonstrate the fundamental feasibility of effectively expressing the same tick-borne encephalitis virus antigen in various vaccine platforms, each with its own advantages and limitations.

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