Exploring the cancer-testis antigen BORIS to design a novel multi-epitope vaccine against breast cancer based on immunoinformatics approaches

Mahdevar, Elham; Safavi, Ashkan; Abiri, Ardavan; Kefayat, Amirhosein; Hejazi‬, ‪Seyed Hossein; Miresmaeili, Seyed Mohsen; Mobarakeh, Vahid Iranpur

doi:10.1080/07391102.2021.1883111

“…In our study, we used tissue-specific antigenic proteins that are highly expressive in liver cancer compared to the BORIS cancer-testis antigen and hydatid cyst wall antigens that are not expressive in liver cells and may not have a role in the treatment and designing of liver cancer vaccines [ 61 , 62 ]. Although these parasite antigens showed substantial immunogenicity and high epitope homology with cancer antigens, however, these proteins are not expressed in the liver [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Experimental Study of Potential CD8+ Trivalent Synthetic Peptides for Liver Cancer Vaccine Development Using Sprague Dawley Rat Models

Zafar

¹

,

Bai

²

,

Guo

³

et al. 2022

BioMed Research International

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Background. Liver cancer (LC) is the most devastating disease affecting a large set of populations in the world. The mortality due to LC is escalating, indicating the lack of effective therapeutic options. Immunotherapeutic agents may play an important role against cancer cells. As immune cells, especially T lymphocytes, which are part of cancer immunology, the design of vaccine candidates for cytotoxic T lymphocytes may be an effective strategy for curing liver cancer. Results. In our study, based on an immunoinformatics approach, we predicted potential T cell epitopes of MHC class I molecules using integrated steps of data retrieval, screening of antigenic proteins, functional analysis, peptide synthesis, and experimental in vivo investigations. We predicted the binding affinity of epitopes LLECADDRADLAKY, VSEHRIQDKDGLFY, and EYILSLEELVNGMY of LC membrane-bounded extracellular proteins including butyrophilin-like protein-2 (BTNL2), glypican-3 (GPC3), and serum albumin (ALB), respectively, with MHC class I molecules (allele: HLA-A ∗ 01:01). These T cell epitopes rely on the level of their binding energy and antigenic properties. We designed and constructed a trivalent immunogenic model by conjugating these epitopes with linkers to activate cytotoxic T cells. For validation, the nonspecific hematological assays showed a significant rise in the count of white blood cells ( 5 × 10 9 / l ), lymphocytes ( 13 × 10 9 / l ), and granulocytes ( 5 × 10 9 / l ) compared to the control after administration of trivalent peptides. Specific immunoassays including granzyme B and IgG ELISA exhibited the significant concentration of these effector molecules in blood serum, indicating the activity of cytotoxic T cells. Granzyme concentration increased to 1050 pg/ml at the second booster dose compared to the control (95 pg/ml), while the concentration of IgG raised to 6 g/l compared to the control (2 g/l). Conclusion. We concluded that a potential therapeutic trivalent vaccine can activate and modulate the immune system to cure liver cancer on the basis of significant outcomes of specific and nonspecific assays.

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“…Altogether, these findings highlight the importance of NcSRS2 as a promising vaccine candidate. “From a biochemical standpoint, a protein is represented in four structural levels, comprising: (i) amino acid sequences as primary structure, (ii) a native spatial form due to main chain atoms ( α -helix and β -fold) as secondary structure, (iii) potential spatial model as a 3D model or tertiary structure, and (iv) number and position of multi-fold subunits in a multi-subunit collection of a protein as quaternary structure” [ 62 – 64 ]. In the first step of this study, we characterized general biochemical features of the protein.…”

Section: Discussionmentioning

confidence: 99%

Neospora caninum SRS2 Protein: Essential Vaccination Targets and Biochemical Features for Next-Generation Vaccine Design

Asghari

¹

,

Kordi

²

,

Maleki

³

et al. 2022

BioMed Research International

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Vaccination is a standout preventive measure to combat neosporosis among cattle herds. The present in silico study was done to evaluate the physicochemical properties and potent immunogenic epitopes of N. caninum SRS2 protein as a possible vaccine candidate. Web-based tools were used to predict physicochemical properties, antigenicity, allergenicity, solubility, posttranslational modification (PTM) sites, transmembrane domains and signal peptide, and secondary and tertiary structures as well as intrinsically disordered regions, followed by identification and screening of potential linear and conformational B-cell epitopes and those peptides having affinity to bind mouse major histocompatibility complex (MHC) and cytotoxic T lymphocyte (CTL). The protein had 401 residues with a molecular weight of 42 kDa, representing aliphatic index of 69.35 (thermotolerant) and GRAVY score of -0.294 (hydrophilic). There were 53 PTM sites without a signal peptide in the sequence. Secondary structure comprised mostly by extended strand, followed by helices and coils. The Ramachandran plot of the refined model showed 90.2%, 8.8%, 0.5%, and 0.5% residues in the favored, additional allowed, generously allowed, and disallowed regions, correspondingly. Additionally, various potential B-cell (linear and conformational), CTL, and MHC-binding epitopes were predicted for N. caninum SRS2. These epitopes could be further utilized in the multiepitope vaccine constructs directed against neosporosis.

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“…The efficacy of epitope selection and screening procedures could be further improved in future studies in order to achieve more accurate, overlapping, and immune-dominant epitopic regions in examined proteins. For instance, ([ 47 , 48 ] provided several steps for the prediction of candidate epitopes. Although, no screening was done in comparison with our study, they utilized a multimethod approach for the prediction of MHC-I and MHC-II binding epitopes.…”

Section: Discussionmentioning

confidence: 99%

Determination of B and T Cell Epitopes in Neospora caninum Immune Mapped Protein-1 (IMP-1): Implications in Vaccine Design against Neosporosis

Nazari

¹

,

Kordi

²

,

Maleki

³

et al. 2022

BioMed Research International

0

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Prevention of neosporosis is advantageous for cattle health and productivity. Previously, several vaccine candidates were nominated for vaccination against Neospora caninum. This study was premised on in silico evaluation of N. caninum IMP-1 in order to determine its physicochemical features and immunogenic epitopes. We employed a wide array of network-based tools for the prediction of antigenicity, allergenicity, solubility, posttranslational modification (PTM) sites, physicochemical properties, transmembrane domains and signal peptide, secondary and tertiary structures, and intrinsically disordered regions. Also, prediction and screening of potential continuous B cell peptides and those epitopes having stringent affinity to couple with mouse major histocompatibility complex (MHC) and cytotoxic T lymphocyte (CTL) receptors were accomplished. The protein had 393 residues with a molecular weight of 42.71 kDa, representing aliphatic index of 85.83 (thermotolerant) and GRAVY score of -0.447 (hydrophilic). There were 47 PTM sites without a signal peptide in the sequence. Secondary structure comprised mostly of extended strand and helices, followed by coils. The Ramachandran plot of the refined model showed 90.1%, 9.9%, 0.0%, and 0.0% residues in the favored, additional allowed, generously allowed, and disallowed regions, correspondingly. Additionally, various potential B cell (linear and conformational), CTL, and MHC binding epitopes were predicted for N. caninum IMP-1. The findings of the present study could be further directed for next-generation vaccine design against neosporosis.

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Exploring the cancer-testis antigen BORIS to design a novel multi-epitope vaccine against breast cancer based on immunoinformatics approaches

Cited by 49 publications

References 136 publications

Experimental Study of Potential CD8+ Trivalent Synthetic Peptides for Liver Cancer Vaccine Development Using Sprague Dawley Rat Models

Experimental Study of Potential CD8+ Trivalent Synthetic Peptides for Liver Cancer Vaccine Development Using Sprague Dawley Rat Models

Neospora caninum SRS2 Protein: Essential Vaccination Targets and Biochemical Features for Next-Generation Vaccine Design

Determination of B and T Cell Epitopes in Neospora caninum Immune Mapped Protein-1 (IMP-1): Implications in Vaccine Design against Neosporosis

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