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Lethal cases of tick-borne encephalitis in previously vaccinated patients have not been described. Modern inactivated vaccines against Tick-borne encephalitis (TBE) are high effective. The TBE cases, preference unfocal forms, are developed in persons with incomplete irregular vaccination. First case of lethal TBE after plural vaccination was described in the Kurgan region, the second case - in the Chelyabinsk region. These very rare unusual cases were studied. Being dominant the Siberian subtype of TBE virus is related with lethal TBE cases in the Chelyabinsk region. Unusual TBE case was developed in patient who had been vaccinated 8 limes with vaccines produced from strains of Far-Eastern TBE subtype («Virion», Tomsk, Chumakov institute, Moscow) and European TBE subtype (Encepur; FSME-Immun). Two years after the last vaccination a focal form of TBE was developed with lethal outcome at 9 th day. Specific antibodies IgM and IgG seroconversion were detected. The TBE virus antigen was detected in brain neurons by immunofluorescent test. Destructed neurons and gliocyles were shown by hystological study in cerebral hemispheres and cerebellum. The Purkinje cells were destructed. Possible reasons of surmounting vaccinal immunity including a genetic difference of vaccine and infection virus strains are discussed.