A Novel Multiepitope Vaccine Against Bladder Cancer Based on CTL and HTL Epitopes for Induction of Strong Immune Using Immunoinformatics Approaches

Abstract

Bladder cancer is well-known cancer in two forms of muscle-invasive and non-muscle-invasive bladder cancer which is responsible for annual deaths worldwide. Common therapies methods are somewhat successful; however, these methods have the limitations such as the side effects of chemotherapy which necessitate the requirement for new preventive methods against bladder cancer. Hence, we explain a novel designed multi-epitope vaccine against bladder cancer using the immunoinformatics tool. Three well-known BLCAP, PRAM, and BAGE4 antigens were evaluated due to most repetitive CTL and HTL epitopes binding. IFNγ and IL10 inducer potential of selected epitopes were investigated, as well as liner and conformational B-cell epitopes. Human beta-defensin 3 and PADRE sequence were added to construct as adjuvants, along with EAAAK, AAY, and GGGS linkers to fuse CTL and HTL epitopes. Results showed this construct encodes a soluble, non-toxic, and non-allergic protein with 70 kDa molecular weight. Modeled 3D structure of vaccine was docked whit Toll-Like Receptors (TLR) of 7/8. Docking, molecular dynamics simulation and MMBPSA analysis confirmed stability of vaccine-TLR complexes. The immunogenicity showed this construct could elicit humoral and cellular immune responses. In silico and immunoinformatics evaluations suggest that this construct is a recombinant candidate vaccine against bladder cancer.