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

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 experimentallydetermined 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 cellbased vaccine against DENV while covering~99% of the global population.

Exploring the therapeutic potential of Hibiscus rosa sinensis synthesized cobalt oxide (Co3O4-NPs) and magnesium oxide nanoparticles (MgO-NPs)

“…The dengue virus (DENV) is transferred into the bodies of mammals (humans) through the bite of female mosquitos known as Aedes Aegypti ( Simo et al 2019 ). The lifespan of the mosquito is brief but after the larvae has the potential of spreading the virus from 4 to 10 days ( Ahmed et al 2020 ). Our study concludes promising potential of biosynthesized NPs as an effective and affordable approach to control the Aedes Aegypti and thus of the dengue fever.…”

In silico T cell epitope identification for SARS-CoV-2: Progress and perspectives

“…Studies that used SARS-CoV immunological data for prediction [ [1] , [2] , [3] , [4] ] are shown in bold font, while all other studies that used peptide-HLA binding prediction methods are in regular font. In silico studies [ [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] ] were obtained from PubMed, while the remaining studies [ [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , ...…”

“…Motivated by the high genetic similarity of SARS-CoV with SARS-CoV-2, multiple in silico studies [ [20] , [21] , [22] , [23] ] used the information of T cell epitopes available from previous SARS-CoV immunological studies to predict likely targets of SARS-CoV-2 T cell responses ( Table 1 ). This approach is well motivated, with cross-reactive T cell epitopes being reported previously for genetically similar viruses [ 27 ], including zika virus, dengue virus, and other flaviviruses [ [28] , [29] , [30] , [31] ]. Interestingly, this was also the basic idea behind the first successful vaccine against an infectious disease, developed by Jenner in 1796, which induced protective immunity against the smallpox virus through inoculation with a related cowpox virus.…”

HLA-dependent variation in SARS-CoV-2 CD8+ T cell cross-reactivity with human coronaviruses

“…Starting with each SARS-CoV-2 peptide and predicted HLAs individually, we find considerable coverage of 55.32% for "LLLD*", while "VQID*" exhibits the lowest predicted coverage of 7.09% (Fig 6D). Similarly to a previous approach by Ahmedid et al 42 , we set out to predict the accumulated global population coverage of the set. We found that 8 peptides collectively produce >90% global coverage, while the entire set is predicted to elicit T cell responses in 92.93% of the global population (Fig 6E).…”