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NPJ Vaccines. 2019 Sep 6;4:38. doi: 10.1038/s41541-019-0133-5. eCollection 2019.

Pre-existing yellow fever immunity impairs and modulates the antibody response to tick-borne encephalitis vaccination.

Author information

1Center for Virology, Medical University of Vienna, Vienna, Austria.
2Division of Infectious Diseases, Department of Medicine, University Hospital of Zurich, Zurich, Switzerland.
3Present Address: Department of Medicine, University Hospital of Leipzig, Leipzig, Germany.
4Present Address: Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.
Present Address: Hookipa Pharma, Vienna, Austria.
6Present Address: Novartis, Rotkreuz, Switzerland.
7Present Address: Department of Medicine, Cantonal Hospital of Winterthur, Winterthur, Switzerland.


Flaviviruses have an increasing global impact as arthropod-transmitted human pathogens, exemplified by Zika, dengue, yellow fever (YF), West Nile, Japanese encephalitis, and tick-borne encephalitis (TBE) viruses. Since all flaviviruses are antigenically related, they are prone to phenomena of immunological memory ('original antigenic sin'), which can modulate immune responses in the course of sequential infections and/or vaccinations. In our study, we analyzed the influence of pre-existing YF vaccine-derived immunity on the antibody response to TBE vaccination. By comparing samples from YF pre-vaccinated and flavivirus-naive individuals, we show that YF immunity not only caused a significant impairment of the neutralizing antibody response to TBE vaccination but also a reduction of the specific TBE virus neutralizing activities (NT/ELISA-titer ratios). Our results point to a possible negative effect of pre-existing cross-reactive immunity on the outcome of flavivirus vaccination that may also pertain to other combinations of sequential flavivirus infections and/or vaccinations.


Viral infection; Virology

Conflict of interest statement

Competing interestsV.B., S.M., A.v.B., J.J., G.T., I.M., K.W., K.S. and F.X.H. declare no competing interests. U.K. declares to have the following competing interest: He has received travel grants and an unrestricted educational grants from Baxter Healthcare Inc. (Austria), which was the manufacturer of the TBE-vaccine used. He also declares that Baxter and its representatives had no influence on the planning, protocol and conduction of the study nor on the analysis and interpretation of the data.

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