T-cell Responses in Individuals Infected with Zika Virus and in Those Vaccinated Against Dengue Virus

Abstract

Background The outbreak of Zika virus (ZIKV) infection in Brazil has raised concerns that infection during pregnancy could cause microcephaly and other severe neurodevelopmental malformations in the fetus. The mechanisms by which ZIKV causes fetal abnormalities are largely unknown. The importance of pre-infection with dengue virus (DENV), or other flaviviruses endemic to Brazil, remains to be investigated. It has been reported that antibodies directed against DENV can increase ZIKV infectivity by antibody dependent enhancement (ADE), suggesting that a history of prior DENV infection might worsen the outcome of ZIKV infection. Methods We used bioinformatics tools to design 18 peptides from the ZIKV envelope containing predicted HLA-I T-cell epitopes and investigated T-cell cross-reactivity between ZIKV-infected individuals and DENV-vaccinated subjects by IFNγ ELISPOT. Results Three peptides induced IFNγ production in both ZIKV-infected subjects and in DENV-vaccinated individuals. Flow cytometry indicated that 1 ZIKV peptide induced a CD4+ T-cell response in DENV-vaccinated subjects. Conclusions We demonstrated that vaccination against DENV induced a T-cell response against ZIKV and identified one such CD4+ T-cell epitope. The ZIKV-reactive CD4+ T cells induced by DENV vaccination and identified in this study could contribute to the appearance of cross-reactive antibodies mediating ADE.

A longitudinal systems immunologic investigation of acute Zika virus infection in an individual infected while traveling to Caracas, Venezuela

“…Collectively, these results detail the global and cell type-specific innate immune responses during an acute ZIKV infection and highlight the rapid development of neutralizing Ab and effector memory T cell responses in a DENV experienced host. These data supports accumulating evidence that prior exposure to DENV accelerates and alters adaptive immune responses likely via the presence of cross-reactive epitopes [16–19, 46]. Measuring time point- and cell type-specific transcriptional signatures of innate vs .…”

CD8 + T cells mediate protection against Zika virus induced by an NS3-based vaccine

“…In addition, our study using human leukocyte antigen (HLA) transgenic mice revealed that the immunodominance pattern of the CD8 + T cell response to ZIKV is altered by previous DENV infection ( 16 ). This is also consistent with human studies reporting that DENV-exposed individuals harbor T cells with cross-reactivity to ZIKV ( 8 – 10 , 34 ) and that DENV exposure before ZIKV infection influences the magnitude and kinetics of the CD8 + T cell response to subsequent ZIKV infection ( 8 ). Thus, both mouse and human studies demonstrate that DENV immunity affords cross-protection against ZIKV and shapes the anti-ZIKV CD8 + T cell response, and mouse studies provide direct evidence that CD8 + T cells protect against ZIKV infection, thereby providing the rationale to develop a protective CD8 + T cell–directed ZIKV vaccine.…”

Cross-reactive Dengue virus-specific CD8+ T cells protect against Zika virus during pregnancy

“…Thus, at early stage of ZIKV infection, prior DENV exposure elicited cross-reactive CD8 + T cells with greater functional activity compared to those expanded during primary ZIKV infection. Recent studies using blood samples from non-pregnant individuals have identified cross-reactive CD8 + T cells in humans 47 , 48 . One of these studies showed that DENV exposure prior to ZIKV infection influenced the magnitude and quality of the CD8 + T cell response 47 , suggesting that prior DENV immunity may shape the anti-ZIKV CD8 + T cell response.…”