Abstract
ABSTRACTPRAME, a cancer/testis antigen, is often expressed abnormally in various cancers, making it a hopeful candidate for cancer immunotherapy. This study aimed to create a vaccine targeting PRAME using immunoinformatics methods. The PRAME protein sequence was obtained from UniProtKB, and a TLR4 agonist sequence from Mycobacterium tuberculosis was included as an adjuvant. Potential T‐cell epitopes were forecasted using the IEDB server and assessed for their antigenicity, lack of allergenicity, and binding affinities to human and murine MHC molecules. Selected epitopes were then combined into a multi‐epitope structure using suitable linkers. The vaccine's physical and chemical properties, 3D structure, and interaction with TLR4 were examined through computational analyses. Five promising MHC‐I and five MHC‐II epitopes from PRAME were pinpointed and incorporated into the multi‐epitope vaccine and the TLR4 agonist adjuvant. The vaccine displayed advantageous biochemical traits, including high stability, solubility, and antigenicity. Molecular docking simulations showcased a steady interaction between the vaccine and TLR4, with a binding energy of −250.5 kcal/mol. Molecular dynamics analyses confirmed the structural stability and minimal distortion of the vaccine‐TLR4 complex. This study introduces a fresh approach to vaccine design targeting PRAME, a cancer‐related antigen. The vaccine structure exhibits promising physical, chemical, and immunological characteristics, suggesting its potential to trigger robust cellular and humoral immune responses against PRAME‐positive cancers.
Published Version
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