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However, cross\u2010reactivity between orthoflaviviruses complicates the diagnosis. Specificity issues may be mitigated by serum neutralization assays (SNT), although the handling of clinically relevant orthoflaviviruses requires biosafety level (BSL) 3 conditions and they have highly divergent viral kinetics and cell tropisms. In the present study, we established a reporter virus particle (RVP)\u2010based SNT in which the infectivity is measured by luminescence and that can be performed under BSL\u20102 conditions. The RVP\u2010based SNT for TBEV exhibited a highly significant correlation with the traditional virus\u2010based SNT (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.8637, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). The RVP\u2010based assay demonstrated a sensitivity of 92.3% (95% CI: 79.7%\u201397.4%) and specificity of 100% (95% CI: 81.6%\u2013100%). We also tested the cross\u2010reactivity of serum samples in RVP\u2010based assays against other orthoflaviviruses (yellow fever virus, dengue virus type 2, Zika virus, West Nile virus and Japanese encephalitis virus). Interestingly, all serum samples which had tested TBEV\u2010positive by ELISA but negative by RVP\u2010based SNT were reactive for antibodies against other orthoflaviviruses. Thus, the RVP\u2010based seroneutralization assay provides an added value in clinical diagnostics as well as in epidemiological studies.<\/jats:p>","DOI":"10.1002\/jmv.29843","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T11:48:22Z","timestamp":1722599302000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A reporter virus particle seroneutralization assay for tick\u2010borne encephalitis virus overcomes ELISA limitations"],"prefix":"10.1002","volume":"96","author":[{"given":"Rahel","family":"Ackermann\u2010G\u00e4umann","sequence":"first","affiliation":[{"name":"Swiss National Reference Centre for Tick\u2010Transmitted Diseases Lausanne Switzerland"},{"name":"ADMED Microbiologie La Chaux\u2010de\u2010Fonds Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis","family":"Dentand","sequence":"additional","affiliation":[{"name":"Institute of Microbiology Lausanne University Hospital, University of Lausanne Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reto","family":"Lienhard","sequence":"additional","affiliation":[{"name":"Swiss National Reference Centre for Tick\u2010Transmitted Diseases Lausanne Switzerland"},{"name":"ADMED Microbiologie La Chaux\u2010de\u2010Fonds Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohsan","family":"Saeed","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Cell Biology Boston University Chobanian and Avedisian School of Medicine, Boston University Boston Massachusetts USA"},{"name":"National Emerging Infectious Diseases Laboratories Boston University Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel E.","family":"Speiser","sequence":"additional","affiliation":[{"name":"Institute of Microbiology Lausanne University Hospital, University of Lausanne Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret R.","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Laboratory of Virology and Infectious Disease The Rockefeller University New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alix T.","family":"Coste","sequence":"additional","affiliation":[{"name":"Swiss National Reference Centre for Tick\u2010Transmitted Diseases Lausanne Switzerland"},{"name":"Institute of Microbiology Lausanne University Hospital, University of Lausanne Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5597-334X","authenticated-orcid":false,"given":"Valeria","family":"Cagno","sequence":"additional","affiliation":[{"name":"Swiss National Reference Centre for Tick\u2010Transmitted Diseases Lausanne Switzerland"},{"name":"Institute of Microbiology Lausanne University Hospital, University of Lausanne Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2019.01.014"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ttbdis.2022.102028"},{"key":"e_1_2_10_4_1","first-page":"531","volume-title":"Handbook of Clinical NEurology","author":"Lindquist L","year":"2014"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60800-4"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-02882-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(02)00819-8"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2017.1389363"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2023.28.2.2200344"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40138-023-00265-4"},{"issue":"1","key":"e_1_2_10_11_1","first-page":"E99","article-title":"Overview of Japanese encephalitis disease and its prevention. 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