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. Supplementary Information The online version contains supplementary material available at 10.1007/s10989-022-10380-7.

Design and In Silico Validation of a Novel MZF-1-Based Multi-Epitope Vaccine to Combat Metastatic Triple Negative Breast Cancer

“…Helper T lymphocytes (HTL) and cytotoxic T lymphocytes (CTL), which bind to MHC class I and class II molecules, are required for the activation of dendritic cells, production of IFN-γ, and triggering apoptosis in tumor cells [ 17 ]. Therefore, an ideal vaccine should trigger both HTL and CTL responses to achieve maximum potency.…”

“…In another study, Akbari et al (2021) utilized a similar kind of pipeline to design two multi-epitope fusion constructs based on HIV-1 and Hsp70 [ 16 ]. Similarly, Jahangirian et al (2022) used immunoinformatics tools to identify potential CTL and HTL epitopes from PRAM, BAGE4, and BLCAP antigens to construct a novel multi-epitope vaccine against bladder cancer [ 17 ]. In another study, Kumar et al (2022) incorporated the epitopes from L1, E5, E6, and E7 oncoproteins of HPV 16 and HPV 18 to formulate a chimeric peptide-based vaccine to combat cervical cancer [ 18 ].…”