Prevalence of antibodies against Tick-Borne Encephalitis Virus in blood donors in the states of Saxony and Berlin/Brandenburg, eastern Germany.

OBJECTIVES: Tick-borne encephalitis virus (TBEV) is a major vector-borne pathogen in Europe, but its true infection burden remains unclear due to the high proportion of asymptomatic infections and the inability of conventional serology to distinguish vaccination- from infection-induced antibodies. We applied a non-structural protein 1 (NS1)-based serological approach to estimate TBEV seroprevalence, incidence, and manifestation index in eastern Germany (Saxony and Berlin/Brandenburg). METHODS: A total of 1,391 anonymized blood donor sera (18-72 years), collected between May and September 2021, were analyzed using commercial TBEV IgG ELISA, an in-house NS1 IgG ELISA, and micro-neutralization testing. RESULTS: Overall, 39.8% of samples were TBEV IgG-positive, indicating vaccination- and/or infection-induced immunity. NS1 antibodies, reflecting past or recent infection, were detected in 1.3% of donors. Estimated vaccination coverage was 38.5%, with higher coverage in Saxony than in Berlin-Brandenburg (45.4% vs. 32.0%). NS1-based analyses revealed a mean annual incidence of 64.7 cases per 100,000 inhabitants, approximately 294-fold higher than notification-based estimates, with a 1000-fold difference in Berlin/Brandenburg. The overall manifestation index was 0.34%, indicating that >99% of infections remain asymptomatic or undiagnosed. Despite higher reported incidence in Saxony, NS1-based estimates indicated substantial infection activity in Berlin/Brandenburg. CONCLUSION: NS1-based serology revealed a markedly underestimated TBEV infection burden and may improve surveillance, identification of emerging risk areas, and targeted vaccination strategies.