Cross-serotypically conserved epitope recommendations for a universal T cell-based dengue vaccine

PLoS Negl Trop Dis. 2020 Sep 21;14(9):e0008676. doi: 10.1371/journal.pntd.0008676. eCollection 2020 Sep.

Abstract

Dengue virus (DENV)-associated disease is a growing threat to public health across the globe. 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. Recent experimental studies suggest that an effective vaccine against DENV should elicit a strong T cell response against all serotypes, 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 reveal a distinct near-binary pattern of epitope conservation across serotypes for a large number of DENV epitopes. Based on the conservation profile, we 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross Reactions / immunology*
  • Dengue / prevention & control
  • Dengue Vaccines / genetics
  • Dengue Vaccines / immunology*
  • Dengue Virus / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans
  • Models, Molecular
  • Protein Structure, Tertiary
  • Proteome
  • Sequence Analysis, Protein
  • Serogroup
  • T-Lymphocytes / immunology*

Substances

  • Dengue Vaccines
  • Epitopes, T-Lymphocyte
  • HLA Antigens
  • Proteome

Grants and funding

This work was supported by the General Research Fund of the Hong Kong Research Grants Council (RGC) (grant numbers 16204519 and 16201620). SFA was also supported by the Hong Kong Ph.D. Fellowship Scheme (HKPFS) (number PF15-10255). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.