In silico analysis of chimeric IL2-MUC1-IFNγ vaccine against breast cancer

Background:Breast cancer is an important cause of cancer-related deaths in Iranian women. Immunotherapy can be effective in treating the advanced breast cancer. We have designed an immunogen derived from, the extracellular domain of MUC1(7tandem repeats/VNTR)as major antigen breast cancer and nearly whole of IFNγ sequence(24 -161)andIL2sequence(21-153) as an vaccine for expression in plant. Methods: Related sequences of MUC1, IL2 and IFNγ were obtained from UniProtKB/Swiss-Prot. The physico-chemical properties were analyzed by the Expasy'sProtParam software. Segments were selected based on prediction of immunogenic epitopes. Linear B-cell epitopes of construct were estimated by bcepred.Discotope1.2 was employed to predictdiscontinuous B-cell epitopes. In general, epitopes having VaxiJen cutoff values of >0.5 was selected. For T-cellepitope prediction. MHC2Pred was employed to predict peptides from the protein binding with MHCII. The chimeric construct codons were optimized based on plant host by EMBOSS .The mRNA secondary structure of the gene was evaluated by the RNAfold software . The prediction of the secondary structure of the protein was performed using the GOR-IV. The 3DJIGSAW was employed for tertiary structure prediction. The tool AccelrysDiscoveryStudio2.5 was used to visualize the modeled3D structures.3Dstructural stability of the protein was evaluated by Swiss-Pdb Viewer software for energy minimization. SDAP allergen library and APPLE software were used to predict the allergenicity of the protein. Results: All of the gained results suggest that this vaccine can work against breast cancer correctly. Conclusion: Before working experimentally we should be confident about the validity of vaccine by in silico analyses

Keywords:

Breast Cancer , Chimeric vaccine , IFNγ , IL2 , MUC1