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Immuno-informatics analyses of important esophageal cancer associated viruses for multi-epitope vaccine design
1Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Dawadmi, Saudi Arabia.
Introduction:
Esophageal cancer (EC) is a highly lethal malignancy characterized by the uncontrolled proliferation of cancerous cells within the esophagus. Despite recent advancements in therapeutic strategies, the prognosis remains poor, underscoring the urgent need for novel preventive and therapeutic approaches. Notably, several oncogenic viruses have been implicated in EC pathogenesis, prompting the exploration of epitope-based vaccines through immunoinformatics.
Methods:
Using immunoinformatics and bioinformatics approaches, we designed a novel multi-epitope vaccine targeting viral agents associated with EC. Protein sequences of ten viral candidates were retrieved from the UniProt database and evaluated for antigenicity using the VaxiJen server. Five highly antigenic proteins derived from Human Cytomegalovirus (HCMV), Human Papillomavirus (HPV), Human Herpesvirus 8 (HHV-8), Human Immunodeficiency Virus (HIV), and Epstein-Barr Virus (EBV) were selected. T cell (CTL and HTL) and B cell (LBL) epitopes were predicted and screened for immunogenicity, allergenicity, and toxicity. The final vaccine construct incorporated β-defensin as an adjuvant and included 3 HTL, 8 CTL, and 8 LBL epitopes. Molecular docking and molecular dynamics (MD) simulations were conducted to assess the binding affinity of the vaccine with Toll-like receptor 3 (TLR3). In silico cloning was also performed using the pET-28a(+) vector in Escherichia coli strain K12.
Results:
The designed vaccine was found to be antigenic, non-allergenic, and non-toxic. Molecular docking revealed strong binding affinity between the vaccine construct and TLR3, which was further supported by MD simulation results indicating stable complex formation. Codon optimization and in silico cloning confirmed the high expression potential of the vaccine in the E. coli expression system.
Discussion:
The in silico analyses suggest that the developed multi-epitope vaccine construct is a promising candidate for preventing EC associated with viral infections. While these findings are encouraging, further experimental validation through in vitro and in vivo studies is essential to confirm the vaccine's safety, immunogenicity, and protective efficacy.
Insights
This study designed a novel multi-epitope vaccine for esophageal cancer (EC) using immunoinformatics. The vaccine targets viral agents and shows promise for preventing virus-associated EC, pending further experimental validation.
Area of Science:
- Oncology
- Immunology
- Bioinformatics
Background:
- Esophageal cancer (EC) is a lethal malignancy with a poor prognosis, necessitating novel preventive and therapeutic strategies.
- Oncogenic viruses are implicated in EC pathogenesis, driving research into epitope-based vaccines.
- Immunoinformatics offers a powerful approach for designing targeted vaccines against complex diseases.
Purpose of the Study:
- To design a novel multi-epitope vaccine targeting viral agents associated with esophageal cancer (EC) using immunoinformatics.
- To predict and screen T cell and B cell epitopes for immunogenicity, allergenicity, and toxicity.
- To evaluate the vaccine construct's binding affinity to Toll-like receptor 3 (TLR3) and its expression potential.
Main Methods:
- Retrieved viral protein sequences from UniProt and evaluated antigenicity using VaxiJen.
- Selected highly antigenic proteins from Human Cytomegalovirus (HCMV), Human Papillomavirus (HPV), Human Herpesvirus 8 (HHV-8), Human Immunodeficiency Virus (HIV), and Epstein-Barr Virus (EBV).
- Predicted and screened T cell (CTL, HTL) and B cell (LBL) epitopes, incorporated β-defensin as an adjuvant, and performed molecular docking, MD simulations, and in silico cloning.
Main Results:
- The designed multi-epitope vaccine construct was found to be antigenic, non-allergenic, and non-toxic.
- Molecular docking and MD simulations demonstrated strong binding affinity and stable complex formation with Toll-like receptor 3 (TLR3).
- In silico cloning confirmed high expression potential in an *Escherichia coli* expression system.
Conclusions:
- The in silico developed multi-epitope vaccine is a promising candidate for preventing virus-associated esophageal cancer (EC).
- Further in vitro and in vivo experimental validation is crucial to confirm the vaccine's safety, immunogenicity, and efficacy.
- This study highlights the potential of immunoinformatics in designing novel therapeutic strategies for EC.
