T Cell Responses Induced by Attenuated Flavivirus Vaccination Are Specific and Show Limited Cross-Reactivity with Other Flavivirus Species

Journal of Virology
Alba GrifoniAlessandro Sette

Abstract

Members of the flavivirus genus share a high level of sequence similarity and often circulate in the same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. In this study, we tested pools of epitopes derived from dengue (DENV), Zika (ZIKV), Japanese encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses by intracellular cytokine staining (ICS) using peripheral blood mononuclear cells (PBMCs) of individuals naturally exposed to DENV or immunized with DENV (TV005) or YF17D vaccine. CD8 T cell responses recognized epitopes from multiple flaviviruses; however, the magnitude of cross-reactive responses was consistently severalfold lower than those to the autologous epitope pools and was associated with lower expression of activation markers such as CD40L, CD69, and CD137. Next, we characterized the antigen sensitivity of short-term T cell lines (TCL) representing 29 different individual epitope/donor combinations. TCL derived from DENV monovalent vaccinees induced CD8 and CD4 T cells that cross-reacted within the DENV serocomplex but were consistently associated with >100-fold-lower antigen sensitivity for most other fl...Continue Reading

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Citations

Oct 6, 2020·Frontiers in Immunology·Maria TrovatoPiergiuseppe De Berardinis
Aug 19, 2020·Vaccines·Mareike KubinskiGuus F Rimmelzwaan
Oct 8, 2020·Nature Reviews. Immunology·Marc LipsitchShane Crotty
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Mar 9, 2021·Frontiers in Immunology·Jessica Badolato-CorrêaLuzia Maria de-Oliveira-Pinto
Apr 2, 2021·Journal of Virology·Blake SchouestDaniela Weiskopf
Apr 7, 2021·The Journal of Infectious Diseases·Ricardo da Silva AntunesAlessandro Sette
Aug 11, 2021·Viruses·Thomas LangerakStephen Vreden

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