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Tick-borne encephalitis (TBE) has a substantial impact on human public health in many parts of Europe and Asia. Effective inactivated purified whole-virus vaccines are in widespread use in TBE-endemic countries. Nevertheless, vaccination breakthroughs (VBTs) with manifest clinical disease do occur, and their specific serodiagnosis was shown to be facilitated by the detection of antibodies to a non-structural protein (NS1) that is produced during virus replication. However, recent data have shown that NS1 is also present in the current inactivated vaccines, with the potential of inducing corresponding antibodies and obscuring a proper interpretation of NS1-antibody assays for diagnosing VBTs. In our study, we quantified anti-virion and anti-NS1 antibody responses after vaccination as well as after natural infection in TBE patients, both without and with a history of previous TBE vaccination (VBTs). We did not find significant levels of NS1-specific antibodies in serum samples from 48 vaccinees with a completed vaccination schedule. In contrast, all TBE patients mounted an anti-NS1 antibody response, irrespective of whether they were vaccinated or not. Neither the dynamics nor the extent of NS1-antibody formation differed significantly between the two cohorts, arguing against substantial NS1-specific priming and an anamnestic NS1-antibody response in VBTs.

Dynamics and Extent of Non-Structural Protein 1-Antibody Responses in Tick-Borne Encephalitis Vaccination Breakthroughs and Unvaccinated Patients