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Within a prospective healthcare worker (HCW) cohort, we assessed the potentially protective role of anti-TBEV antibodies against SARS-CoV-2 infection. Among 3352 HCW, those with\u2009\u2265\u20091 previous TBEV vaccination (n\u2009=\u20092018, 60%) showed a reduced risk of SARS-CoV-2 seroconversion (adjusted odds ratio: 0.8, 95% CI: 0.7\u20131.0, P\u2009=\u20090.02). However, laboratory testing of a subgroup of 26 baseline and follow-up samples did not demonstrate any neutralizing effect of anti-TBEV antibodies against SARS-CoV-2 in live-virus neutralization assay. However, we observed significantly higher anti-TBEV antibody titers in follow-up samples of participants with previous TBEV vaccination compared to baseline, both TBEV neutralizing (p\u2009=\u20090.001) and total IgG (P\u2009&lt;\u20090.0001), irrespective of SARS-CoV-2 serostatus. Based on these data, we conclude that the observed association of previous TBEV vaccination and reduced risk of SARS-CoV-2 infection is likely due to residual confounding factors. The increase in TBEV follow-up antibody titers can be explained by natural TBEV exposure or potential non-specific immune activation upon exposure to various pathogens, including SARS-CoV-2. We believe that these findings, although negative, contribute to the current knowledge on potential cross-immunity against SARS-CoV-2 from previous immunizations.<\/jats:p>","DOI":"10.1038\/s41598-021-03685-y","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T11:14:56Z","timestamp":1639739696000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["No neutralizing effect of pre-existing tick-borne encephalitis virus antibodies against severe acute respiratory syndrome coronavirus-2: a prospective healthcare worker study"],"prefix":"10.1038","volume":"11","author":[{"given":"Philipp","family":"Kohler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hulda R.","family":"Jonsdottir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenz","family":"Risch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Vernazza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahel","family":"Ackermann-G\u00e4umann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian R.","family":"Kahlert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"3685_CR1","unstructured":"https:\/\/coronavirus.jhu.edu\/map.html Last Accessed: 28 June 2021 [cited 2021 28 June]."},{"key":"3685_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmni.2020.100760","volume":"38","author":"R Lalaoui","year":"2020","unstructured":"Lalaoui, R. et al. 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