Abstract
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.
Highlights
There was no significant difference between vaccinated and unvaccinated patients, neither with respect to the quantity nor with respect to the time course of Nonstructural protein 1 (NS1) antibodies produced, providing no evidence for enhanced virus replication in vaccination breakthroughs (VBTs)
Serum samples of confirmed Tick-borne encephalitis (TBE) cases with previous TBE vaccinations (VBT) were available from 18 patients: the first samples were obtained upon hospitalization, and one to two follow-up samples were collected within six weeks after the first sample
A matched control group consisted of 18 TBE patients without flavivirus vaccinations, of which a similar number of archived primary and follow-up samples was available in a comparable period
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. TBE NS1 antibody assays and analyses have been published [13,14,15,16,17], quantitative data of the levels and kinetics of NS1 IgG antibodies produced in the course of VBTs compared to infections in unvaccinated individuals are not available so far. Such quantitative analyses could provide clues as to enhancement phenomena and potential differences of the extent of virus replication in these patient groups. There was no significant difference between vaccinated and unvaccinated patients, neither with respect to the quantity nor with respect to the time course of NS1 antibodies produced, providing no evidence for enhanced virus replication in VBTs
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