Tick-borne encephalitis virus (TBEV) infection can manifest as disease of variable severity, ranging from subclinical infection to severe disease with neurological involvement and potentially fatal outcome. Although TBE is recognized as a major public health problem in Europe, the true burden of disease is potentially underestimated. Here, we investigated TBEV-specific antibody prevalence, infection incidence, and seroreversion and antibody decline rates in a prospective Swiss healthcare worker (HCW) cohort. We screened serum samples from 1444 HCWs between June and October 2020, and from a subset again between August and September 2021, using a TBEV envelope (E) protein IgG ELISA. Positive samples underwent further analysis with a TBEV non-structural protein 1 (NS1) IgG ELISA, and seroconversions in unvaccinated individuals were confirmed by seroneutralization testing. Questionnaire data were used to determine vaccination status and risk factors. TBEV E protein-specific IgG prevalence was 72.1% (95% CI 68.2-75.7%) in TBEV-vaccinated and 6% (95% CI 4.4-7.8%) in unvaccinated individuals. The estimated annual incidence of infection was 735/100,000. Age was the only factor significantly associated with seroprevalence. The seroreversion rate in unvaccinated individuals was 30.3% within one year, which is almost ten times higher than in vaccinated individuals (3.4%, annual decline rate 8.0%). NS1-specific IgG antibodies were six times more common in vaccinated than unvaccinated HCWs. In conclusion, undetected TBEV infections are common, and infection incidence is much higher than reported clinical cases. Individuals with abortive infections have high antibody decline and seroreversion rates. Whether lifelong protection is conferred and by which immune subsets remain unclear.

Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic

Division of Infectious Diseases and Hospital Epidemiology Kantonsspital Baden Baden Switzerland

Division of Infectious Diseases Infection Prevention and Travel Medicine Cantonal Hospital of St Gallen St Gallen Switzerland

Institute of Mathematical Statistics and Actuarial Science University of Bern Bern Switzerland

Interregional Blood Transfusion SRC Bern Switzerland

Laboratory of Arbovirology Institute of Parasitology Biology Centre of the Czech Academy of Sciences Ceske Budejovice Czech Republic

Laboratory of Emerging Viral Infections Veterinary Research Institute Brno Czech Republic

Microbiologie ADMED Analyses et Diagnostics Médicaux La Chaux de Fonds Switzerland

Swiss National Reference Center for Tick Transmitted Diseases Lausanne Switzerland

Thurgau Hospital Group Division of Infectious Diseases and Hospital Epidemiology Muensterlingen Switzerland

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