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Reverse Vaccinology and Immunoinformatics Strategy to Screen Oncogenic Proteins and Development of a Multiepitope
Samir Shaikh1, Daksh Kunchala1, Mansi Patel2
1Parul Institute of Applied Sciences, Parul University, Vadodara, India.
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.
Insights
A novel multi-epitope peptide vaccine was computationally designed to target oral cancer, showing high immunogenic potential. This vaccine candidate effectively stimulates both cell-mediated and humoral immunity, offering a promising new avenue for oral cancer prevention.
Area of Science:
- Oncology
- Vaccinology
- Computational Biology
Background:
- Oral cancer presents a high mortality rate despite existing treatments.
- There is a critical need for more effective and targeted oral cancer therapies.
- Multi-epitope vaccines offer a promising strategy for cancer prevention and treatment.
Purpose of the Study:
- To design a novel multi-epitope peptide vaccine for oral cancer prevention using computational methods.
- To identify potential vaccine targets and immunogenic epitopes through immunoinformatics.
- To evaluate the vaccine construct's binding affinity and immune response potential.
Main Methods:
- Employed a reverse vaccinology approach integrated with machine learning and immunoinformatics tools.
- Identified LYN Proto-Oncogene and AKT1 as key targets based on their roles in cancer regulation.
- Selected B and T cell epitopes with favorable physicochemical properties, non-toxicity, and high antigenicity.
Main Results:
- LYN and AKT1, crucial protein kinases in cancer, were identified as suitable vaccine targets.
- A vaccine construct incorporating selected immune epitopes and a Toll-like receptor 4 (TLR4) agonist adjuvant demonstrated strong binding affinity to TLR4.
- Immune simulations predicted robust immune cell activation and a sustained IgG/IgM response for up to a year.
Conclusions:
- The designed multi-epitope peptide vaccine exhibits significant immunogenic potential against oral cancer.
- The vaccine is predicted to induce both cell-mediated and humoral immunity.
- This computational approach provides a foundation for developing a novel oral cancer vaccine.
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