In silico analysis of VEGFR2 and c-MET in consideration with immunologic facts: Implications for mRNA vaccine design against breast cancer.

Abstract

Active immunization in cancer therapy can induce tumor-specific immune responses without harming the normal cells. Among these approaches, especially after the success of FDA-approved mRNA vaccines, this platform has gained much more attention as a promising strategy. This study focused on designing an mRNA-based vaccine against breast cancer by selecting two angiogenic elements that are overexpressed in breast cancer cells, in an immunoinformatic approach. Epitopes were filtered based on antigenicity, toxicity, and allergenicity to ensure that they could elicit both T and B-cell-mediated immune responses. Molecular docking simulations analyzed their interactions with Major Histocompatibility Complex (MHC) molecules. The final vaccine construct included 10 selected epitopes linked with appropriate linkers and optimized for codon usage, ensuring ideal GC content and codon adaptation index. Protein docking analyses showed strong interactions with appropriate binding energies, while molecular dynamics simulations confirmed the docked complex stability. Immune simulations revealed high antibody titers, cytokine response, and an increase in immune cells such as B Cells, Cytotoxic T Lymphocyte (CTL) cells, and Helper T Lymphocyte (HTL) cells. Based on these findings, this vaccine design presents a strong candidate for an mRNA-based breast cancer vaccine, with further development currently underway.