Designing a multi-epitope based vaccine to combat Kaposi Sarcoma utilizing immunoinformatics approach.
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ABSTRACT:
SUBMITTER: Chauhan V
PROVIDER: S-EPMC6385272 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Currently, no approved vaccine is available against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes severe respiratory disease. The spike glycoprotein is typically considered a suitable target for MERS-CoV vaccine candidates. A computational strategy can be used to design an antigenic vaccine against a pathogen. Therefore, we used immunoinformatics and computational approaches to design a multi-epitope vaccine that targets the spike glycoprotein of MERS-CoV. After using numerous immunoinformatics tools and applying several immune filters, a poly-epitope vaccine was constructed comprising cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon-gamma (IFN-γ)-inducing epitopes. In addition, various physicochemical, allergenic, and antigenic profiles were evaluated to confirm the immunogenicity and safety of the vaccine. Molecular interactions, binding affinities, and the thermodynamic stability of the vaccine were examined through molecular docking and dynamic simulation approaches, during which we identified a stable and strong interaction with Toll-like receptors (TLRs). In silico immune simulations were performed to assess the immune-response triggering capabilities of the vaccine. This computational analysis suggested that the proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat viral infections; however, experimental evaluations remain necessary to verify the exact safety and immunogenicity profile of this vaccine.
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Project description:BackgroundMonkeypox virus is an enveloped DNA virus that belongs to Poxviridae family. The virus is transmitted from rodents to primates via infected body fluids, skin lesions, and respiratory droplets. After being infected with virus, the patients experience fever, myalgia, maculopapular rash, and fluid-filled blisters. It is necessary to differentiate monkeypox virus from other poxviruses during diagnosis which can be appropriately envisioned via DNA analysis from swab samples. During small outbreaks, the virus is treated with therapies administered in other orthopoxviruses infections and does not have its own specific therapy and vaccine. Consequently, in this article, two potential peptides have been designed.MethodsFor the purpose of designing a vaccine, protein sequences were retrieved followed by the prediction of B- and T-cell epitopes. Afterward, vaccine structures were predicted which were docked with toll-like receptors. The docked complexes were analyzed with iMODS. Moreover, vaccine constructs nucleotide sequences were optimized and expressed in silico.ResultsCOP-B7R vaccine construct (V1) has antigenicity score of 0.5400, instability index of 29.33, z-score of - 2.11-, and 42.11% GC content whereas COP-A44L vaccine construct (V2) has an antigenicity score of 0.7784, instability index of 23.33, z-score of - 0.61, and 48.63% GC content. It was also observed that COP-A44L can be expressed as a soluble protein in Escherichia coli as compared to COP-B7R which requires a different expression system.ConclusionThe obtained results revealed that both vaccine constructs show satisfactory outcomes after in silico investigation and have significant potential to prevent the monkeypox virus. However, COP-A44L gave better results.
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Project description: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.
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Project description:Streptococcus pneumoniae is one of the major precarious pathogens accountable for over 1.2 million fatalities annually. The key drivers for pneumococcal vaccine development involve high morbidity and mortality in over one million cases, especially in very young children and the elderly. In this study, immunoinformatics was integrated with subtractive proteomics to find antigenic proteins for designing a multi-epitope vaccine against S. pneumoniae. As prospective vaccine targets, the developed pipeline identified two antigenic proteins, i.e., penicillin-binding protein and ATP synthase subunit. Several immunoinformatics and bioinformatics resources were used to forecast T- and B-cell epitopes from specific proteins. By employing a mixture of five cytotoxic T-cell lymphocytes, six helper T-cell lymphocytes, and seven linear B-cell lymphocyte epitopes, a 392 amino acid-long vaccine was designed. To enhance immune responses, the designed vaccine was coupled with a cholera enterotoxin subunit B adjuvant. The designed vaccine was highly antigenic, non-allergenic, and stable for human usage. The stability of the vaccine with toll-like receptor-4 was evaluated by molecular docking and molecular dynamic simulation. In addition, immunological simulation was performed to test its real-world potency. The vaccine codon was then cloned in silico. Overall, this study paves the way for the development of a multi-epitope S. pneumoniae vaccine under laboratory conditions. Furthermore, the current findings warrant for the experimental validation of the final multi-epitope vaccine construct to demonstrate its immunological reinforcing capability and clinical applicability.
| S-EPMC10407660 | biostudies-literature
Project description:Ongoing COVID-19 outbreak has raised a drastic challenge to global public health security. Most of the patients with COVID-19 suffer from mild flu-like illnesses such as cold and fever; however, few percentages of the patients progress from severe illness to death, mostly in an immunocompromised individual. The causative agent of COVID-19 is an RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite these debilitating conditions, no medication to stop the disease progression or vaccination is available till now. Therefore, we aimed to formulate a multi-epitope vaccine against SARS-CoV-2 by utilizing an immunoinformatics approach. For this purpose, we used the SARS-CoV-2 spike glycoprotein to determine the immunodominant T- and B-cell epitopes. After rigorous assessment, we designed a vaccine construct using four potential epitopes from each of the three epitope classes such as cytotoxic T-lymphocytes, helper T-lymphocyte, and linear B-lymphocyte epitopes. The designed vaccine was antigenic, immunogenic, and non-allergenic with suitable physicochemical properties and has higher solubility. More importantly, the predicted vaccine structure was similar to the native protein. Further investigations indicated a strong and stable binding interaction between the vaccine and the toll-like receptor (TLR4). Strong binding stability and structural compactness were also evident in molecular dynamics simulation. Furthermore, the computer-generated immune simulation showed that the vaccine could trigger real-life-like immune responses upon administration into humans. Finally, codon optimization based on Escherichia coli K12 resulted in optimal GC content and higher CAI value followed by incorporating it into the cloning vector pET28+(a). Overall, these results suggest that the designed peptide vaccine can serve as an excellent prophylactic candidate against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.
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Project description:BackgroundIt seems that several members of intestinal gut microbiota like Streptococcus bovis, Bacteroides fragilis, Helicobacter pylori, Fusobacterium nucleatum, Enterococcus faecalis, Escherichia coli, Peptostreptococcus anaerobius may be considered as the causative agents of Colorectal Cancer (CRC). The present study used bioinformatics and immunoinformatics approaches to design a potential epitope-based multi-epitope vaccine to prevent CRC with optimal population coverage.MethodsIn this study, ten amino acid sequences of CRC-related pathogens were retrieved from the NCBI database. Three ABCpred, BCPREDS and LBtope online servers were considered for B cells prediction and the IEDB server for T cells (CD4+ and CD8+) prediction. Then, validation, allergenicity, toxicity and physicochemical analysis of all sequences were performed using web servers. A total of three linkers, AAY, GPGPG, and KK were used to bind CTL, HTL and BCL epitopes, respectively. In addition, the final construct was subjected to disulfide engineering, molecular docking, immune simulation and codon adaptation to design an effective vaccine production strategy.ResultsA total of 19 sequences of different lengths for linear B-cell epitopes, 19 and 18 sequences were considered as epitopes of CD4+ T and CD8+ cells, respectively. The predicted epitopes were joined by appropriate linkers because they play an important role in producing an extended conformation and protein folding. The final multi-epitope construct and Toll-like receptor 4 (TLR4) were evaluated by molecular docking, which revealed stable and strong binding interactions. Immunity simulation of the vaccine showed significantly high levels of immunoglobulins, helper T cells, cytotoxic T cells and INF-γ.ConclusionFinally, the results showed that the designed multi-epitope vaccine could serve as an excellent prophylactic candidate against CRC-associated pathogens, but in vitro and animal studies are needed to justify our findings for its use as a possible preventive measure.
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Project description:Peptostreptococcus anaerobius is an anaerobic bacterium, which has been found selectively en-riched in the fecal and mucosal microbiota of colorectal cancer (CRC) patients. Emerging evidence suggest P. anaerobius may contribute to the development of CRC in human. In this study, we designed a multi-epitope chimeric vaccine against P. anaerobius PCWBR2, a recently identified adhesin that interacts directly with colon cell lines by binding α2/β1 integrin frequently overexpressed in human CRC tumors and cell lines. Immunoinformatics tools predicted six cytotoxic T lymphocyte epitopes, five helper T lymphocyte epitopes, and six linear B lymphocyte epitopes. The predicted epitopes were joined with AAY or GPGPG linkers and a previously reported TLR4 agonist was added to the vaccine construct's N terminal as an adjuvant using EAAAK linkers and the order of epitopes was optimized. Further in silico analysis revealed that the vaccine construct possesses satisfactory antigenicity, allergenicity, solubility, physicochemical properties, adjuvant-TLR4 molecular docking, and immune profile characteristics. Our study provided a promising design for vaccines against P. anaerobius.
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Project description:The COVID-19 disease is caused by SARS-CoV-2 and spreading rapidly worldwide with extremely high infection rate. Since effective and specific vaccine is not available to combat the deadly COVID-19, the objective of our study was to design a multi-epitope vaccine using immunoinformatics approach with translational implications. Nucleocapsid (N) protein of SARS-CoV-2 is stable, conserved and highly immunogenic along with being less prone to mutations during infection, which makes it a suitable candidate for designing vaccine. In our study, B- and T-cells epitopes were identified from N protein and screened based on crucial parameters to design the multi-epitope vaccine construct. Additionally, human beta-defensin-2 was incorporated into the vaccine construct as an adjuvant along with suitable linkers followed by its further evaluation based on crucial parameters including allergenicity, antigenicity, stability etc. Combined major histocompatibility complexes (MHC-I and MHC-II) binding epitopes presented broader population coverage of the vaccine throughout the world. The three-dimensional structure of vaccine candidate implied strong interaction with toll-like receptor 3 (TLR3) using molecular docking. The vaccine-TLR3 complex was observed to be highly stable during simulation and electrostatic free energy was foremost contributor for stabilization of the structure. Subsequently, in silico cloning of vaccine candidate was carried out to generate the construct into pET-28a(+) expression vector succeeded by its virtual confirmation. Altogether, our results advocate that the designed vaccine candidate could be an effective and promising weapon to fight with COVID-19 infection worldwide.
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Project description:Coxsackievirus B (CVB) is one of the major viral pathogens of human myocarditis and cardiomyopathy without any effective preventive measures; therefore, it is necessary to develop a safe and efficacious vaccine against CVB. Immunoinformatics methods are both economical and convenient as in-silico simulations can shorten the development time. Herein, we design a novel multi-epitope vaccine for the prevention of CVB by using immunoinformatics methods. With the help of advanced immunoinformatics approaches, we predicted different B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes, respectively. Subsequently, we constructed the multi-epitope vaccine by fusing all conserved epitopes with appropriate linkers and adjuvants. The final vaccine was found to be antigenic, non-allergenic, and stable. The 3D structure of the vaccine was then predicted, refined, and evaluated. Molecular docking and dynamics simulation were performed to reveal the interactions between the vaccine with the immune receptors MHC-I, MHC-II, TLR3, and TLR4. Finally, to ensure the complete expression of the vaccine protein, the sequence of the designed vaccine was optimized and further performed in-silico cloning. In conclusion, the molecule designed in this study could be considered a potential vaccine against CVB infection and needed further experiments to evaluate its safety and efficacy.
| S-EPMC9682020 | biostudies-literature
Project description:Marburg virus disease (MVD) caused by the Marburg virus (MARV) generally appears with flu-like symptoms and leads to severe hemorrhagic fever. It spreads via direct contact with infected individuals or animals. Despite being considered to be less threatening in terms of appearances and the number of infected patients, the high fatality rate of this pathogenic virus is a major concern. Until now, no vaccine has been developed to combat this deadly virus. Therefore, vaccination for this virus is necessary to reduce its mortality. Our current investigation focuses on the design and formulation of a multi-epitope vaccine based on the structural proteins of MARV employing immunoinformatics approaches. The screening of potential T-cell and B-cell epitopes from the seven structural proteins of MARV was carried out through specific selection parameters. Afterward, we compiled the shortlisted epitopes by attaching them to an appropriate adjuvant and linkers. Population coverage analysis, conservancy analysis, and MHC cluster analysis of the shortlisted epitopes were satisfactory. Importantly, physicochemical characteristics, human homology assessment, and structure validation of the vaccine construct delineated convenient outcomes. We implemented disulfide bond engineering to stabilize the tertiary or quaternary interactions. Furthermore, stability and physical movements of the vaccine protein were explored using normal-mode analysis. The immune simulation study of the vaccine complexes also exhibited significant results. Additionally, the protein-protein docking and molecular dynamics simulation of the final construct exhibited a higher affinity toward toll-like receptor-4 (TLR4). From simulation trajectories, multiple descriptors, namely, root mean square deviations (rmsd), radius of gyration (Rg), root mean square fluctuations (RMSF), solvent-accessible surface area (SASA), and hydrogen bonds, have been taken into account to demonstrate the inflexible and rigid nature of receptor molecules and the constructed vaccine. Inclusively, our findings suggested the vaccine constructs' ability to regulate promising immune responses against MARV pathogenesis.
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