Peptide MegaPools Approach to Evaluate the Dengue-Specific CD4 and CD8 T-Cell Response

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BACKGROUND: Being central players in the adaptive immunity, the study of T-cell responses is crucial in both natural infections and vaccine-induced immunity. In this study, we assessed the antigen-specific T-cell responses to dengue virus (DENV) to identify the most immunogenic antigen for evaluating dengue-specific T-cell responses. METHODS: Patients with dengue disease and subjects vaccinated with the QDENGA (TAK-003) vaccine (before and three months after vaccination) were enrolled. The T-cell-specific response was measured by ELISPOT and Activation Induced Markers (AIM) assay following PBMC stimulation either with DENV1-4 CD4 and CD8 MegaPools (MP) or serotype-specific DENV peptide pools at different concentrations. RESULTS: We found that both DENV1-4 CD4 MP (at 1 µg/mL) and CD8 MP (at 5 µg/mL), which encompass all four DENV serotypes, elicited specific T-cell responses in patients with dengue infection independent of the infecting serotype. In contrast, selected serotype-specific DENV peptide pools have a lower ability to induce a measurable T-cell response. Moreover, DENV1-4 CD4 and CD8 MPs, at the highest concentrations, are suitable candidates to evaluate the dengue-specific T-cell response in vaccinated subjects. CONCLUSIONS: These findings support the use of the MP approach to investigate dengue-specific T-cell response to monitor the response during the infection and after vaccine administration.