In silico design of a triple-negative breast cancer vaccine by targeting cancer testis antigens

Abstract

Introduction: Triple-negative breast cancer (TNBC) is an important subtype of breast cancer, which occurs in the absence of estrogen, progesterone and HER-2 receptors. According to the recent studies, TNBC may be a cancer testis antigen (CTA)-positive tumor, indicating that the CTA-based cancer vaccine can be a treatment option for the patients bearing such tumors. Of these antigens (Ags), the MAGE-A family and NY-ESO-1 as the most immunogenic CTAs are the potentially relevant targets for the development of an immunotherapeutic way of the breast cancer treatment. Methods: In the present study, immunoinformatics approach was used to design a multi-epitope peptide vaccine to combat the TNBC. The vaccine peptide was constructed by the fusion of three crucial components, including the CD8+ cytotoxic T lymphocytes (CTLs) epitopes, helper epitopes and adjuvant. The epitopes were predicted from the MAGE-A and NY-ESO-1 Ags. In addition, the granulocyte-macrophage-colony-stimulating factor (GM-CSF) was used as an adjuvant to promote the CD4+ T cells towards the T-helper for more strong induction of CTL responses. The components were conjugated by proper linkers. Results: The vaccine peptide was examined for different physiochemical characteristics to confirm the safety and immunogenic behavior. Furthermore, the 3D-structure of the vaccine peptide was predicted based on the homology modeling approach using the MODELLER v9.17 program. The vaccine structure was also subjected to the molecular dynamics simulation study for structure refinement. The results verified the immunogenicity and safety profile of the constructed vaccine as well as its capability for stimulating both the cellular and humoral immune responses. Conclusion: Based on our in-silico analyses, the proposed vaccine may be considered for the immunotherapy of TNBC.

A multi-method and structure-based in silico vaccine designing against Echinococcus granulosus through investigating enolase protein

“…Since the designed minigene vaccine construct consists of immunogenic BCEs and HTEs along with two immunogenic intramolecular adjuvant and suitable peptide spacers, it may have a high ability to induce the innate and adaptive anti-echinococcus immune responses within the host body. 13,72,73…”

“…81 Therefore, the helper T-cell receptor specific epitopes are the main components for vaccine designing against infectious diseases 13,61 as well as cancers. 73 The estimated physicochemical parameters of the final vaccine construct showed the vaccine protein contains aliphatic side chains and is hydrophobic, thermos-stable, and basic in nature. 82 The 3D structure of the EgEnolase, TLR-2, TLR-4, and DLA-DRB1*01101 was modeled with the minimum structural error (Fig.…”

A Candidate Multi-Epitope Vaccine Against Pathogenic Chandipura Vesiculovirus Identified using Immunoinformatics.

“…Several research groups have recently applied similar strategy to design a multiepitope vaccine against Klebsiella pneumoniae [88], Kaposi Sarcoma [20], Pseudomonas aeruaginosa [103], Epstein Barr virus [104], Malaria [105], Hendra virus [106] and Nipah virus [107]. Similar approaches have also been used for developing vaccine against cancer antigens [22,[108][109][110] The proposed mechanism of action was also predicted for the nal vaccine model (Fig. 13).…”

Prophylactic domain-based vaccine against SARS-CoV-2, causative agent of COVID-19 pandemic

“…The MD simulation procedure was carried out at 310 K by placing the model into a cubic box that had a suitable size and two Na+ ions to neutralize the environment. Subsequently, the RMSD graph was drawn for the analysis of the dynamic behavior of the constructed model 74 . The local and overall quality of the improved 3D model was checked using online web-servers, including PROCHECK 75 , verify3D 76 , ERRAT 77 .…”