Feature Papers represent the most advanced research with significant potential for high impact in the field. Feature
Papers are submitted upon individual invitation or recommendation by the scientific editors and undergo peer review
prior to publication.

The Feature Paper can be either an original research article, a substantial novel research study that often involves
several techniques or approaches, or a comprehensive review paper with concise and precise updates on the latest
progress in the field that systematically reviews the most exciting advances in scientific literature. This type of
paper provides an outlook on future directions of research or possible applications.

Dengue virus belonging to the family Flaviviridae and its four serotypes are responsible for dengue infections, which extend over 60 countries in tropical and subtropical areas of the world including Pakistan. During the ongoing dengue outbreak in Pakistan (2022), over 30,000 cases have been reported, and over 70 lives have been lost. The only commercialized vaccine against DENV, Dengvaxia, cannot be administered as a prophylactic measure to cure this infection due to various complications. Using machine learning and reverse vaccinology approaches, this study was designed to develop a tetravalent modified nucleotide mRNA vaccine using NS1, prM, and EIII sequences of dengue virus from Pakistani isolates. Based on high antigenicity, non-allergenicity, and toxicity profiling, B-cell epitope, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) putative vaccine targets were predicted. Molecular docking confirmed favorable interactions between T-cell epitopes and their respective HLA alleles, while normal mode analysis validated high-affinity interactions of vaccine proteins with immune receptors. In silico immune simulations confirmed adequate immune responses to eliminate the antigen and generate memory. Codon optimization, physicochemical features, nucleotide modifications, and suitable vector availability further ensured better antigen expression and adaptive immune responses. We predict that this vaccine construct may prove to be a good vaccinal candidate against dengue virus in vitro as well.
dengue virus; mRNA vaccines; reverse vaccinology; molecular docking; normal mode analysis; immune simulations
dengue virus; mRNA vaccines; reverse vaccinology; molecular docking; normal mode analysis; immune simulations

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