Immunoinformatics approach to design chimeric CD70-Peptide Vaccines against Renal cell carcinoma

Renal cell carcinoma (RCC) serves as the cause of majority of cancer-related deaths globally. CD70 is excessively expressed and linked to the advancement of RCC. Hence, the aim of the current investigation is to create a multi-epitope vaccine targeting overexpressed CD70 using an immunoinformatics technique. Herein, multi-epitope vaccines were constructed in silico by linking specific epitopes of CD70 protein for helper T lymphocytes and CD8+ T lymphocytes. In order to boost its immunogenicity, sequences of cell penetrating peptide (CPP), penetratin (pAntp), as well as TNF-α whole sequence were bound to the N-terminal and C-terminal of the CD70 epitopes. Chimeric vaccines were assessed computationally in terms of antigenicity, allergenicity, peptide toxicity, population coverage and physicochemical properties. Moreover, various analyses were additionally conducted on refined 3D constructs, comprising of structural B–cell epitope prediction, molecular docking, molecular dynamics simulation, immune simulation analysis and in silico cloning of the vaccine constructs. All vaccines contain antigenic, non-toxic, non-allergenic, and accessible B cell epitopes and can provide extensive population coverage globally. Vaccine constructs exhibit favorable physicochemical characteristics. Binding affinity of the chimeric vaccines with the TLR 2, 3, 4, 5 and TNF receptor were relatively stable and were affected by the alignment of vaccine components. Furthermore, the designed candidate vaccines entail the ability to regulate both the humoral and cellular immune reactions. In-silico codon optimization and cloning of the vaccine nucleic acid sequence have also been accomplished using the pET28a plasmid. Overall, results showed that chimeric CD70 vaccines are potential vaccine against RCC.