Dobler et al.
Tick-borne encephalitis virus vaccination breakthrough infections in Germany – a retrospective analysis from 2001-2018
Clin. Microbiol. Infect. 2020, in press, doi.org/10.1016/j.cmi.2019.12.001

Currently licensed TBE vaccines are highly effective. However, breakthrough infections occur, and it is debated if these infections may be associated with a more severe course of infection compared to disease in non-immunized patients. The underlying mechanism for this phenomenon may be explained by antibody dependent enhancement (ADE), which is known from other flaviviral infections, especially by dengue virus.

During the period 2001 to 2018, a total of 6,073 TBE cases have been notified in Germany, for which the vaccination status was available for 5,777 patients (95.1%). TBE disease severity was analyzed for four vaccination categories. These were i) „unvaccinated“, ii) „ever vaccinated“: individuals had received at least one vaccine dose, iii) „vaccinated, protected“: individuals who had received more than one vaccine dose (primary immunization and possibly booster doses) and assumed to be protected, and iv) „vaccinated, no protection assumed at symptom onset“: a subset of „ever vaccinated“-group, which was assumed not to be protected due to non-regular vaccination course.

Comparing unvaccinated patients to those „ever vaccinated“ with at least one dose (n=334) an OR 2.73 was found for fatal outcome, but this result did not reach statistical significance. Patients never having received a TBE vaccine dose were more likely hospitalized that patients who had received at least one vaccine dose (OR 0.72). Analyses for the symptoms „CNS symptoms“, and „myelitis“ revealed no differences between the groups „without any vaccination“ and „patients with at least one vaccination“ (OR 0.86 and 1.30, respectively). In comparison, vaccinated patients with no assumed protection at onset of symptoms had no significantly higher risk for a fatal outcome or myelitis, and there was a significantly decreased risk of hospitalization and for development of CNS symptoms compared to unvaccinated patients. More comparisons between the four groups are described and led the authors to the conclusion that their findings could neither verify that vaccination breakthrough infections might cause a more severe disease than infections in non-vaccinated individuals nor prove a clear ADE phenomenon. Patients without any vaccination were more often hospitalized showing the efficacy of TBE vaccine, even with one single dose.

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