Pre-existing T Cell Memory against Zika Virus.

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Zika virus (ZIKV) and dengue virus (DENV) are mosquito-borne flaviviruses co-endemic in many regions.
• Cross-reactive T cell responses between ZIKV and DENV are observed, but specific epitope targets are not well-defined.
• Understanding preexisting immunity is crucial for managing flavivirus infections and developing vaccines.

Purpose of the Study:

• To comprehensively map T cell epitopes targeted by cross-reactive immunity to ZIKV in individuals with prior DENV exposure.
• To investigate the immunodominance patterns and characteristics of these cross-reactive T cell responses.
• To assess the implications for flavivirus immunity, diagnostics, and vaccine strategies.

Main Methods:

• Analysis of human blood samples from DENV-endemic regions (Nicaragua, Sri Lanka) collected before the 2016 ZIKV spread.
• In vitro expansion of T cells from ZIKV-unexposed, DENV-seropositive donors.
• Epitope mapping, computational HLA binding analysis, and identification of cross-reactive peptide recognition.

Main Results:

• Identification of 93 ZIKV T cell epitopes, with immunodominance influenced by antigen size and DENV sequence similarity.
• Confirmation of epitope immunogenicity and demonstration that cross-reactive T cells recognize ZIKV peptides homologous to DENV sequences.
• Evidence that CD4+ T cell responses originated from the memory T cell compartment.

Conclusions:

• Preexisting immunity to DENV significantly shapes T cell responses to ZIKV in co-endemic areas.
• Defined ZIKV epitopes provide targets for understanding flavivirus cross-reactivity and developing immune interventions.
• Findings inform strategies for flavivirus vaccine development and diagnostic tool creation.