Abstract
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.
Highlights
Samples were derived from groups of flavivirus-naive and yellow fever (YF)-prevaccinated individuals who had received tick-borne encephalitis (TBE) vaccination according to a basic vaccination schedule at time points 0, 4, and 24 weeks (Table 1 and Fig. 1c)
In the pools of the flavivirus-naive group, TBE ELISA and neutralization tests (NT) both showed a substantial increase of antibody titers after the 2nd dose, followed by a decline and a further strong boost
Our analyses show that the immune response to TBE vaccination can be substantially altered by pre-existing YF vaccine-induced immunity
Summary
Explosive outbreaks and dramatic expansions of endemic regions have been documented in the recent past for Zika, West Nile (WN), and dengue viruses (Den), underlining the impact of flaviviruses as emerging pathogens.[1,2,3,4] All flaviviruses are antigenically related and can induce broadly flavivirus cross-reactive antibodies; crossprotection, is not observed among distantly related flaviviruses.[5,6,7] In contrast, cross-reactive antibodies may even have a disease-enhancing effect during a subsequent exposure with a different flavivirus.[6,8] In general, the immunological memory to cross-reactive antigenic sites and the formation of immune-complexes can modulate the antibody response in sequential infections or immunizations with antigenically related viruses or immunogens, respectively. This phenomenon has been referred to as ‘original antigenic sin’ (OAS)[9,10,11] and is especially relevant in the context of annual infections and vaccinations with drifting and shifting influenza viruses.[12,13] in the case of flaviviruses, OAS phenomena can play an important role,[14,15] as a result of sequential exposures to flaviviruses that co-circulate in the same geographical regions, global travel-related exposures, and/or immunization with different flavivirus vaccines, which is the topic of the present work
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
