Stiasny et al.
Dynamics and extent of non-structural protein 1-antibody responses in tick-borne encephalitis vaccination breakthroughs and unvaccinated patients.
Viruses. 2021; 13:1007. doi: 10.3390/v13061007.

Two vaccines are offered in the EU which confer high protection rates against TBE. However, vaccination breakthroughs (VBTs) sporadically occur – even in individuals who have received several injections. TBE vaccines contain glycoprotein E as main immunogenic structural antigen, while non-structural proteins like NS1 were thought not to be a component of TBE vaccines until recently, small amounts of NS1 have been detected in TBE vaccines (see Newsletter February 2020). Patients who have been infected with the TBE virus develop antibodies to NS1 (see Snapshot week 9/2020 and Newsletter April 2020). So far, quantitative data of the levels and kinetics of NS1 IgG antibodies produced during VBTs compared to infections in unvaccinated individuals are missing.

A study has been carried out using sera obtained i) from 10 patients with VBT, ii) a control group of 18 TBE patients without flavivirus vaccinations, iii) a group of 48 individuals with complete TBE vaccination, iv) a group of six individuals with threefold vaccination against TBE, JE, and YF and v) a group of 27 individuals with flavivirus-negative sera.

Unvaccinated TBE patients were all NS1-positive. No NS1-antibodies were found in individuals immunized with TBE vaccine. All patients developed NS1-antibodies independent, whether they had been vaccinated or not prior to infection. The kinetics in patients with VBTs was not significantly different from those patients who had not been vaccinated, and there was also no difference in quantity of NS1-antibodies indicating that there was no booster against NS1 and that the vaccines used did not contain NS1 which may have primed the individuals. Since the extent of produced antibodies may be related to the disease severity of patients, these results show no indication for a vaccine/antibody induced enhancement which has been discussed for flavivirus infections including TBE.

The detection of NS1-antibodies in sera of patients is a reliable indicator of TBE virus infection.

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