2020

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Browsing 2020 by Author "Anila Ilyas"

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    In silico designing of a multi-epitope vaccine candidate against denguevirus specific to HLA alleles of the USA populations
    (UMT Lahore, 2020) Anila Ilyas
    Dengue is a single-stranded RNA virus, belonging to the genus Flavivirus, and causes systematic viral infection among humans. There are four different serotypes of this virus reported in the literature, including DENV1, DENV2, DENV3, and DENV4. Its outbreak started in Africa, Asia, and America then spread to the whole world. Currently, there is no authorized vaccine against dengue, and only one vaccine named dengvaxia was approved, in 2015, which was also proved to be less effective for the USA populations. Therefore, it is the need of the time to develop a tetravalent vaccine, which would be effective for all the serotypes of the dengue virus in this population. The present study involves the screening of highly immunogenic and non-allergenic B and T-cell epitopes, from the three proteins of the dengue virus, NS1, NS3, and E, through IEDB. The binding affinities of all selected T-cell epitopes with the USA-specific HLA alleles, retrieved via AFND, were further checked using IEDB binding affinity tools. Three epitopes, having the strongest binding affinities with the HLA alleles, immunogenic, and non-allergenic natures, were considered efficient for designing a multi-epitope construct, with the GSGSG linker among the adjacent epitopes. The structural modeling and validation of all possible multi-epitope constructs revealed that variant 1 was the most stable among all with the proper folding and structural integrity. Moreover, the population coverage of this construct was 67.67% for the USA populations, suggesting this construct as the favorable candidate for designing a tetravalent vaccine, against the four serotypes of dengue virus, against these populations. Still, additional experimental studies are required to confirm its soluble expression, non-allergenic nature, and immunogenic effects on diseased subjects.