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All flaviviruses are antigenically related and anamnestic responses due to prior immunity can modulate antibody specificities in subsequent infections or vaccinations. In our study, we analyzed the induction of broadly flavivirus cross\u2010reactive antibodies in tick\u2010borne encephalitis (TBE) and DEN patients without or with prior flavivirus exposure through TBE and\/or YF vaccination, and determined the contribution of these antibodies to TBE and dengue virus (DENV) neutralization. In addition, we investigated the formation of cross\u2010reactive antibodies in TBE\u2010vaccination breakthroughs (VBTs). A TBEV infection without prior YF or TBE vaccination induced predominantly type\u2010specific antibodies. In contrast, high levels of broadly cross\u2010reactive antibodies were found in samples from TBE patients prevaccinated against YF as well as in DEN patients prevaccinated against TBE and\/or YF. While these cross\u2010reactive antibodies did not neutralize TBEV, they were effective in neutralizing DENV. This discrepancy points to structural differences between the two viruses and indicates that broadly cross\u2010reactive epitopes are less accessible in TBEV than in DENV. In TBE VBT infections, type\u2010specific antibodies dominated the antibody response, thus revealing no difference from that of unvaccinated TBE patients. Our results emphasize significant differences in the structural properties of different flaviviruses that have an impact on the induction of broadly cross\u2010reactive antibodies and their functional activities in virus neutralization.<\/jats:p>","DOI":"10.1002\/jmv.29245","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T23:57:40Z","timestamp":1701129460000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effect of previous heterologous flavivirus vaccinations on human antibody responses in tick\u2010borne encephalitis and dengue virus infections"],"prefix":"10.1002","volume":"95","author":[{"given":"Lena","family":"Ro\u00dfbacher","sequence":"first","affiliation":[{"name":"Center for Virology Medical University of Vienna Vienna 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