Quantitative comparison of the cross-protection induced by tick-borne encephalitis virus vaccines based on European and Far Eastern virus subtypes

Abstract Tick-borne encephalitis virus (TBEV) is a flavivirus of wide geographic distribution and the causative agent of tick-borne encephalitis (TBE), an infection of the central nervous system. TBE has the highest incidence rate in Russia, where locally produced as well as Western European vaccines for the prevention of TBE are available. The Western European vaccines are based on TBE viruses that belong to the European subtype, while the Russian vaccines are based on Far Eastern subtype viruses. The question of to which extent vaccination with a vaccine based on the European subtype is effective in protecting against the heterologous Far Eastern virus subtype – and vice versa – has not been answered conclusively. Here we immunized mice with TBE vaccines based on European and Far Eastern subtype viruses, and used an unbiased hybrid virus test system to determine cross-neutralizing antibody titers and cross-protective efficacy. All vaccines tested elicited cross-protective responses against the heterologous strains, similar to those induced against the respective homologous vaccine strains. These data, therefore, fully support the use of TBE vaccines in geographic regions where virus subtypes heterologous to the vaccine strains are prevalent.