Title : Development of a polyepitope-based immunogen for inducing cellular immunity against all dengue virus serotypes
Abstract:
Dengue, a significant global health challenge, is caused by four co-circulating serotypes (DENV 1-4) of the virus. Viral infections not only result in health complications and fatalities among infected individuals, but it also depletes limited resources intended for preventing infections. The only licensed vaccine against dengue exhibit variable efficacy based on host factors and primary stimulate humoral response. It also has low efficacy in children and dengue-naive individuals. The development of an effective vaccine is critical to minimize the spread and impact of this infection.
In our study, we address this challenge by developing a polyepitope-based immunogen that induces active cellular immunity against DENV all serotypes. Our preclinical investigation explored the potential of priming CB6F1 mice with CD8+ T cell epitopes from all four DENV serotypes simultaneously to induce protective cellular immunity against all serotypes. A chimeric peptide, comprised of T-cell epitopes from conserved domains of the DENV envelope protein, was designed and validated using advanced immunoinformatics tools.
Subsequently, the cellular immune response was demonstrated by the development of IFNγ and TNFα producing CD8+ T cells in immunized mice. These specific CD8+ T cell responses were elicited against a pool of DENV peptide epitopes from all serotypes, evident in both ex-vivo and in-vitro experiments. These results provides a robust basis for conducting in-vivo evaluations, representing a substantial advancement towards comprehensive and effective dengue vaccine.
