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Designing a novel SOX9 based multi-epitope vaccine to combat metastatic triple-negative breast cancer using
HemaNandini Rajendran Krishnamoorthy1, Ramanathan Karuppasamy2
1Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Abstract:
Immunotherapies are a promising treatment option especially for the management of TNBC owing to its higher levels of tumour-associated antigens together with higher mutational load. Of note, the administration of preventive vaccines in the early stage of the cancer holds promise for effective disease management. Therefore, the present study aimed to develop a novel multi-epitope peptide-based vaccination against TNBC employing SOX9, which has recently been recognized as a key regulator of TNBC metastasis. The immunodominant regions from the SOX9 protein were computed and assessed based on their ability to elicit both T and B lymphocyte mediated responses. The resultant epitopes were fused using appropriate linkers (EAAAK, KK, AAY and GPGPG) and adjuvant (50S ribosomal protein L7/L12) to enhance the vaccine's immunogenicity. The physicochemical properties and population coverage were also anticipated for the constructed vaccine. Adding together, docking and dynamics simulation studies were performed on the modelled vaccine against TLR-4 to provide insight into the stability. Finally, the designed vaccine was cloned into the pET28 (+) vector and immunological simulation studies were carried out. These results demonstrate that our designed vaccine had the potency to trigger humoral and cellular immune responses. Based on these collective evidences, the final proposed vaccine could be an interesting therapeutics for the management of TNBC in the near future. Schematic representation of an efficient vaccine design framework by combining the range of immunoinformatics strategies.
Insights
A novel multi-epitope peptide vaccine targeting SOX9 shows promise for triple-negative breast cancer (TNBC) management. This computational study designed a vaccine with potential to elicit strong humoral and cellular immune responses against TNBC.
Area of Science:
- Immunology
- Computational Biology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) presents a significant therapeutic challenge.
- Immunotherapy, particularly vaccines, offers a promising avenue for TNBC management due to high tumor antigen levels.
- SOX9 is identified as a key regulator of TNBC metastasis, making it a potential vaccine target.
Purpose of the Study:
- To design a novel multi-epitope peptide-based vaccine against TNBC utilizing the SOX9 protein.
- To computationally assess the immunogenicity and stability of the designed vaccine.
Main Methods:
- Identification and selection of immunodominant regions from SOX9 for T and B cell responses.
- Fusion of selected epitopes with linkers and an adjuvant (50S ribosomal protein L7/L12).
- In silico analysis including physicochemical properties, population coverage, docking, molecular dynamics simulations, and immunological simulations.
Main Results:
- The designed vaccine construct demonstrated favorable physicochemical properties and population coverage.
- Molecular simulations indicated stability and potential interaction with TLR-4.
- Immunological simulations predicted the vaccine's capacity to induce both humoral and cellular immune responses.
Conclusions:
- The in silico designed multi-epitope peptide vaccine targeting SOX9 is a potential candidate for TNBC therapeutics.
- This vaccine design framework, integrating immunoinformatics strategies, shows promise for future cancer vaccine development.
- Further experimental validation is warranted to confirm the efficacy of this novel TNBC vaccine.
