Poster Presentation 12th Australasian Virology Society Meeting 2024

Cross-serotypically conserved epitope recommendations for a universal T cell-based dengue vaccine   (#118)

Syed Faraz Ahmed 1
  1. University of Melbourne, Melbourne, Australia, VICTORIA, Australia

Dengue virus (DENV)-associated disease is a growing threat to public health across the globe. In recent year, the geographical footprint of DENV is increasing and becoming endemic in more countries. Co-circulating as four different serotypes, DENV poses a unique challenge for vaccine design as immunity to one serotype predisposes a person to severe and potentially lethal disease upon infection from other serotypes. Emerging evidence suggests that an effective vaccine should elicit a strong T cell response against all serotypes of DENV., which could be achieved by directing T cell responses toward cross-serotypically conserved epitopes while avoiding serotype-specific ones. Here, we used experimentally determined DENV T cell epitopes and patient-derived DENV sequences to assess the cross-serotypic variability of the epitopes. We define the conservation profile of these epitopes and identify a set of 55 epitopes that are highly conserved in at least 3 serotypes. Most of the highly conserved epitopes lie in functionally important regions of DENV non-structural proteins. By considering the global distribution of human leukocyte antigen (HLA) alleles associated with these DENV epitopes, we identify a potentially robust subset of HLA class I and class II restricted epitopes that can serve as targets for a universal T cell-based vaccine against DENV while covering ~99% of the global population. In addition, we assess the temporal conservation profile of all known DENV T cell epitopes and assess their potential towards T cell escape. We also present an easy-to-use dashboard accompanying our analysis to facilitate the research community in understanding the emerging landscape of DENV T cell epitopes.

  1. Ahmed SF, Quadeer AA, Barton JP, McKay MR. Cross-serotypically conserved epitope recommendations for a universal T cell-based dengue vaccine. Weiskopf D, editor. PLOS Neglected Tropical Diseases. 2020 Sep;14(9):e0008676.