Reverse Vaccinology and Immunoinformatics Strategy to Screen Oncogenic Proteins and Development of a Multiepitope Peptide Vaccine Targeting Protein Kinases against Oral Cancer: An in-silico Study.

BACKGROUND

Despite standard therapies and immunotherapies, the mortality rate of patients with oral cancer remains high. Therefore, there is a need for more effective and targeted treatments. Multi-epitope vaccines have been developed for various cancers owing to their easy protection and delivery. However, no multi-epitope vaccine has been designed to prevent oral cancer.

METHODS

In this study, a reverse vaccinology approach, along with various machine-learning integrated immunoinformatics tools, was used to design a multi-epitope peptide vaccine.

RESULTS

Using an integrated computational method, LYN Proto-Oncogene and AKT1 were identified as good candidates. Both LYN and AKT1 are protein kinases and plays a central role in regulating various outputs, such as proliferation, differentiation, apoptosis, and migration in cancer. These proteins were selected because of their favorable physicochemical properties, non-allergic, non-toxic, and antigenic nature. Suitable B and T cell epitopes were identified based on their physicochemical characteristics, toxicity, allergenicity, antigenicity, and immunogenicity. A vaccine was constructed using these immune epitopes and TLR4 agonist as an adjuvant. Molecular dynamics simulation suggests strong binding affinity for Toll-like receptor 4. Furthermore, immune simulation studies suggest the activation of immune cells and a strong IgG/IgM response for approximately one year.

CONCLUSION

We propose that the vaccine developed has high immunogenic potential and able to induce both cell mediated and humoral immunity against oral cancer.