Exploring the cancer-testis antigen BORIS to design a novel multi-epitope vaccine against breast cancer based on immunoinformatics approaches

Abstract

Recently, cancer immunotherapy has gained lots of attention to replace the current chemoradiation approaches and multi-epitope cancer vaccines are manifesting as the next generation of cancer immunotherapy. Therefore, in this study, we used multiple immunoinformatics approaches along with other computational approaches to design a novel multi-epitope vaccine against breast cancer. The most immunogenic regions of the BORIS cancer-testis antigen were selected according to the binding affinity to MHC-I and II molecules as well as containing multiple cytotoxic T lymphocyte (CTL) epitopes by multiple immunoinformatics servers. The selected regions were linked together by GPGPG linker. Also, a T helper epitope (PADRE) and the TLR-4/MD-2 agonist (L7/L12 ribosomal protein from mycobacterium) were incorporated by A(EAAAK)3A linker to form the final vaccine construct. Then, its physicochemical properties, cleavage sites, TAP transport efficiency, B cell epitopes, IFN-γ inducing epitopes and population coverage were predicted. The final vaccine construct was reverse translated, codon-optimized and inserted into pcDNA3.1 to form the DNA vaccine. The final vaccine construct was a stable, immunogenic and non-allergenic protein that contained numerous CTL epitopes, IFN-γ inducing epitopes and several linear and conformational B cell epitopes. Also, the final vaccine construct formed stable and significant interactions with TLR-4/MD-2 complex according to molecular docking and dynamics simulations. Moreover, its world population coverage for HLA-I and HLA-II were about 93% and 96%, respectively. Taking together, these preliminary results can be used as an appropriate platform for further experimental investigations. Communicated by Ramaswamy H. Sarma