Immunoinformatics-Guided Design and Molecular Dynamics Evaluation of a Multi-Epitope Vaccine Targeting High-Risk HPV-16 and HPV-18

Abstract

HPV types 16 and 18 are oncogenic genotypes responsible for a substantial proportion of cervical cancer cases. Although prophylactic HPV vaccines are available, they do not eliminate established infections. In this study, an immunoinformatics approach was used to design a multi-epitope vaccine derived from the E5 and E7 proteins of HPV-16 and HPV-18. CTL, HTL, and B-cell epitopes were selected according to predicted antigenicity, non-allergenicity, non-toxicity, HLA-binding potential, and population coverage. The selected epitopes were assembled with suitable linkers and an adjuvant to generate 405-amino-acid vaccine construct. The construct had a predicted molecular weight of 45.49 kDa, theoretical pI of 9.37, instability index of 29.00, aliphatic index of 71.65, and GRAVY score of −0.360. It was predicted to be antigenic and non-allergenic, while combined MHC class I and II epitope analysis indicated greater than 90% global population coverage. The three-dimensional structure was subsequently predicted, refined, and evaluated for structural quality.Molecular docking was used to examine interactions between the vaccine construct and the selected immune receptor, followed by 100-ns molecular dynamics simulation in Desmond. The simulation revealed conformational adjustments, region-specific flexibility, coordinated residue motions, and changes in structural compactness over the trajectory. Overall, the findings provide a computational basis for further experimental evaluation of HPV-16/18 E5/E7-derived multi-epitope vaccine. Experimental studies are required to confirm its expression, safety, immunogenicity, and potential therapeutic relevance.

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