Design of Multi-Epitope Subunit Vaccine for Salivary Proteins of Aedes Aegypti: An Immuno-Informatics Approach

Vector borne diseases such as dengue cause significant morbidity in developing tropical regions including the Indian sub-continent. Dengue is caused by dengue virus (DENV) that is transmitted within the human race by its vector i.e. female Aedes aegypti mosquito. The salivary proteins of vectors help in blood feeding and have the ability to elicit an immune response in humans. Therefore, salivary proteins may be an effective target for design of vaccines to prevent the transmission of the disease causing pathogens into the human host. The present study was undertaken to identify candidate T-cell and B-cell epitopes for design of an effective multi–epitope subunit vaccine against salivary proteins of Aedes aegypti using an immuno-informatics based approach. The sequences of previously reported immunogenic salivary proteins of Aedes aegypti were retrieved from UniProtKB and analyzed using various in-silico tools such as NetCTL, IEDB resource server, AntigenPro and AllerTOP for identification of T-cell and B-cell epitopes. The identified 9-mer and 15-mer peptide sequences of TC and TH cell epitopes were combined with suitable TLR-4 agonist, linkers and adjuvant for design of the 714 aa multi-epitope subunit vaccine construct whose tertiary structure was predicted using I-TASSER server followed by refinement and validation using GalaxyRefine and RAMPAGE servers. Finally protein-protein docking of the vaccine construct and TLR-4, which is involved in anti-parasitic immune response, was performed using ClusPro. The binding pose and binding energy of the docked structure indicated significant interactions and that the multi-epitope subunit vaccine construct would be able to elicit an immune response.