Computational Approaches To Design Multi Epitope-Based Vaccine Designing of Dengue virus -2 Enveloped Protein For Dengue Virus

Abstract

Dengue Fever (DF) is a viral disease transmitted by mosquitoes and is a global concern. A successful vaccine for dengue should induce both neutralizing antibodies and cell-mediated immunity. However, no vaccine currently exists for DF. A multi-epitope vaccine offers a promising strategy for preventing such infections. Objective: To create a dengue virus-2 strain multi-epitope vaccine that is safe, non-allergic, and stimulates a strong immune response. Methods: Leveraging in silico tools, we retrieved and analyzed Dengue virus-2 protein sequences, determining antigenicity using VaxiJen version 2.0 and assessing allergenicity using AllerTop. T-cell epitopes were identified via Immune Epitope Database (IEBD) server for Major Histocompatibility Complex -I (MHC-I) and Major Histocompatibility Complex -II (MHC-II) binding and B-cell epitopes were anticipated through IEBD Linear Epitope Prediction Tool v2.0. Analysis of population coverage estimated the prevalence of MHC alleles interacting with the identified epitopes. A multi-epitope vaccine construct integrated adjuvants, universal linkers, and epitopes, evaluated for physicochemical properties, toxicity, secondary, and tertiary structures. Results: Antigenicity analysis identified highly antigenic Dengue virus-2 protein sequences with low allergenicity. T-cell epitopes revealed multiple epitopes with diverse MHC-I and MHC-II affinity, encompassing conserved regions for potential universal vaccine development. Nine non-toxic, non-allergenic B-cell epitopes were identified. Population coverage analysis demonstrated over 71% prevalence of MHCs binding to identified epitopes across diverse populations. Physicochemical assessments revealed favorable characteristics, including immunogenicity and stability. Tertiary structure prediction illustrated the vaccine's 3D arrangement, validated through Ramachandran plots, exhibiting high-quality protein structure. Conclusions: This multieiptope based vaccine is more immunogenic but further in-vitro and in-vivo study is required for its clinical use