Currently available vaccines against tick-borne encephalitis (TBE) are highly effective; however, they do not ensure 100% protection. Laboratory diagnostics of TBE in vaccinated patients remains poorly developed. Objective. To compare the dynamics of humoral immunity in unvaccinated and vaccinated patients and to develop an algorithm of specific laboratory diagnostics of TBE. Patients and methods. We have tested 276 unvaccinated and 59 vaccinated patients using enzyme-linked immunosorbent assay for the detection of IgG and IgM against antigens of tick-borne encephalitis virus (TBEV). In hemagglutination inhibition assay, we used dry TBEV reagent. TBEV RNA was detected using reverse transcription polymerase chain reaction (RT-PCR). Results. We have identified three types of humoral immunity dynamics in vaccinated and unvaccinated patients: seroconversion, stable antibody titers, and negative (reverse) antibody dynamics with an at least 4-fold decrease in antibody levels. Among 39 vaccinated individuals, 18 patients demonstrated seroconversion, while 16 patients had stable antibody titers and 4 patients had negative dynamics. Patients with chronic TBE demonstrated different variants of humoral immunity dynamics. Discussion. We discuss the variants of antibody dynamics described above and diagnostic methods on the example of vaccinated patients. In individuals with stable antibody titers, we used an original method for detecting the dynamics of antibodies against Siberian strain of TBEV. Conclusion. In case of seroconversion, the level of specific immunity in vaccinated patients was higher than that in unvaccinated patients and healthy individuals vaccinated against TBE. Negative antibody dynamics is the rarest variant of humoral immunity development. The diagnosis of TBE in patients with stable antibody titers is confirmed by the detection of TBEV antigen, increasing serum levels of IgM, detection of TBEV RNA in the cerebrospinal fluid, and isolation of the virus. Keywords: vaccinated patients, humoral immunity, diagnosis, tick-borne encephalitis