Design and in silico analysis of a novel peptide-based multiepitope vaccine against glioblastoma multiforme by targeting tumor-associated macrophage

Abstract

CD204 is a distinct indicator for tumor-associated macrophages (TAMs) in glioma. Evidence indicates that CD204-positive TAMs are involved in the aggressive behavior of various types of cancers. This study was conducted to develop a new and effective peptide-based vaccine for GBM, specifically targeting CD204. Epitopes of the target protein were identified using NetMHCpan 4.1a, NetMHCIIpan-4.0, and ABCpred tools. Subsequently, the predicted epitopes were evaluated using bioinformatics tools to assess their antigenicity, non-allergenicity, immunogenicity, non-toxicity, and potential to stimulate the production of IL-4 and IFN-γ in HTL epitopes. Selected T-cell epitopes demonstrated a robust binding affinity with the particular HLA alleles. Finally, four HTL epitopes, three CTL epitopes, and two B-cell epitopes, jointed via linkers and adjuvant, were used for the final vaccine construct design. Analysis disclosed that the developed vaccine demonstrated robust antigenic properties while proving soluble, stable, non-toxic, and non-allergenic. Additionally, molecular docking studies and molecular dynamics simulations confirmed a robust correlation between the designed vaccine and TLR-2 and TLR-4 immune receptors. The molecular docking results demonstrated a strong interaction between the newly developed vaccine and TLR2 (−895.1 kcal/mol) and TLR4 (−881.0 kcal/mol) receptors. During the simulation, the vaccine-TLR2 and vaccine-TLR4 complexes exhibited binding energies of −113.41 and −106.61 kcal/mol, respectively. Analysis by different bioinformatic tools indicated the potential of the designed vaccine in immune stimulation and a significant elevation in IgG and IgM antibodies, T-helper cells, T-cytotoxic cells, INF-γ, IL-2, and IL-4. Research findings show that the newly designed multi-epitope vaccine is promising in providing long-term immunity against GBM and offers a promising therapeutic alternative.

Keywords

• Glioblastoma cancer
• Tumor-associated macrophages
• CD204
• Immunotherapy
• Molecular docking
• Molecular dynamics (MD) simulation