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Designing of Peptide Based Multi-Epitope Vaccine Construct against Gallbladder Cancer Using Immunoinformatics and Computational Approaches.

ABSTRACT: Gallbladder cancer (GBC) is an aggressive and difficult to treat biliary tract carcinoma with a poor survival rate. The aim of this study was to design a peptide-based multi-epitope vaccine construct against GBC using immunoinformatics approaches. Three proteins implicated in the progression of GBC were selected for B and T cell epitope prediction and the designing of the potential vaccine construct. Seven CTL, four HTL and six Bcell epitopes along with a suitable adjuvant were selected and connected using linkers for designing the vaccine construct. The secondary and tertiary models of the designed vaccine were generated and satisfactorily validated. A Ramachandran plot of the final 3D model showed more than 90% of the residues in allowed regions and only 0.4% in disallowed regions. The binding affinity of a vaccine construct with TLR 2, 3 and 4 receptors was assessed through molecular docking and simulation. The average numbers of hydrogen bonds for vaccine-TLR 2, 3 and 4 complexes in the simulation were 15.36, 16.45, and 11.98, respectively, and remained consistent over a 100 ns simulation period, which is critical for their function. The results of this study provide a strong basis for further evaluation through in vitro/in vivo experimental validation of the safety and efficacy of the designed vaccine construct.

SUBMITTER: Dar MA

PROVIDER: S-EPMC9696659 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Designing of Peptide Based Multi-Epitope Vaccine Construct against Gallbladder Cancer Using Immunoinformatics and Computational Approaches.

Dar Mukhtar Ahmad MA Kumar Pawan P Kumar Prakash P Shrivastava Ashish A Dar Muneer Ahmad MA Chauhan Richa R Trivedi Vinita V Singh Ashutosh A Khan Eshan E Velayutham Ravichandiran R Dhingra Sameer S

Vaccines 20221031 11

Gallbladder cancer (GBC) is an aggressive and difficult to treat biliary tract carcinoma with a poor survival rate. The aim of this study was to design a peptide-based multi-epitope vaccine construct against GBC using immunoinformatics approaches. Three proteins implicated in the progression of GBC were selected for B and T cell epitope prediction and the designing of the potential vaccine construct. Seven CTL, four HTL and six Bcell epitopes along with a suitable adjuvant were selected and conn ...[more]

PMID: 36366359

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Project description:Introduction: The current incidence of the novel coronavirus disease has shown only small reductions of cases and has become a major public health challenge. Development of effective vaccines against the virus is still being encouraged such as multi-epitope vaccines designed from the components of SARS-CoV-2 including its spike, nucleocapsid and ORF1a proteins. Since the addition of adjuvants including HABA protein and L7/L12 ribosomal are considered helpful to increase the effectiveness of the designed vaccine, we proposed to design multiepitope vaccines by two different adjuvants. Methods: We used the IEDB server to predict BCL and TCL epitopes that were characterized using online tools including VaxiJen, AllPred and IL-10 Prediction. The selected epitopes were further constructed into multiepitope vaccines. We also added two different adjuvants to the vaccine components in order to increase the effectiveness of the vaccines. The 3D-structured vaccines were built using trRosetta. They were further docked with different Toll-like-receptors (TLR 3, 4 and 8) and the entry receptor of SARS-CoV-2, ACE2 using ClusPro, PatchDock and refined by FireDock. All structures were visualized by USCF Chimera and PyMOL. Results: In this study, we succeeded in designing two different candidate vaccines by the addition of HABA protein and L7/L12 ribosomal as adjuvants. The two vaccines were almost equally good in terms of their physicochemical properties and characteristics. Likewise, their strong interactions with TLR3 4, 8 and ACE2 show the lowest energy level of both was estimated at more than -1,000. Interactions of vaccines with ACE2 and TLRs are essential for activation of immune responses and production of antibodies. Conclusion: The two designed and constructed multiepitope vaccine have good characteristics and may have the potential to activate humoral and cellular immune responses against SARS-CoV-2. Further research is worth considering to confirm the findings of this study.

Project description:IntroductionLeptospirosis, caused by Leptospira interrogans, is a neglected zoonotic disease that poses a significant global health risk to both humans and animals. The rise of antimicrobial resistance and the inefficacy of existing vaccines highlight the urgent need for new preventive strategies.MethodsAn immunoinformatics approach was employed to design a multi-epitope subunit vaccine (MESV) against leptospirosis. B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes were selected from five key Leptospira proteins. These epitopes were fused with a heparin-binding hemagglutinin (HBHA) adjuvant and appropriate linkers to construct the broad-spectrum vaccine. The physicochemical properties of the vaccine were assessed, including antigenicity, immunogenicity, allergenicity, and conservation. The vaccine's 3D structure was modeled, optimized, and validated. Molecular docking, molecular dynamics simulations, and MM-GBSA analysis were performed to assess the vaccine's binding interactions with Toll-like receptors (TLR2 and TLR4). Immune simulations and in silico cloning were also conducted to evaluate the vaccine's immune response and expression potential.ResultsThe MESV demonstrated high antigenicity, immunogenicity, non-allergenicity, and conservation across different Leptospira strains. Population coverage analysis revealed that T-cell epitopes significantly interacted with HLA molecules, covering 95.7% of the global population. Molecular docking showed strong and stable binding with TLR2 and TLR4, with binding energies of -1,357.1 kJ/mol and -1,163.7 kJ/mol, respectively. Molecular dynamics simulations and MM-GBSA analysis confirmed the stability of these interactions and accurately calculated the intermolecular binding free energies. Immune simulations indicated robust B and T cell responses, and in silico cloning demonstrated that the vaccine could be successfully expressed in E. coli.DiscussionThese findings suggest that MESV is a promising candidate for leptospirosis prevention, providing robust immune responses and broad population coverage. However, further in vivo studies are necessary to validate its efficacy and safety.

Project description:COVID-19 caused by SARS-CoV-2 was declared a global pandemic by WHO (World Health Organization) in March, 2020. Within 6 months, nearly 750,000 deaths are claimed by COVID-19 across the globe. This called for immediate social, scientific, technological, public and community interventions. Considering the severity of infection and the associated mortalities, global efforts are underway to develop preventive measures against SARS-CoV-2. Among the SARS-CoV-2 target proteins, Spike (S) glycoprotein (a.k.a S Protein) is the most studied target known to trigger strong host immune response. A detailed analysis of S protein-based epitopes enabled us to design a novel B-cell-derived T-cell Multi-epitope-based peptide (MEBP) vaccine candidate. This involved a systematic and comprehensive computational protocol consisting of prediction of dual-purpose epitopes and designing an MEBP vaccine construct. This was followed by 3D structure validation, MEBP complex interaction studies, in silico cloning and vaccine dose-based immune response simulation to evaluate the immunogenic potency of the vaccine construct. The dual-purpose epitope prediction protocol was designed such that the same epitope elicits both humoral and cellular immune response unlike the earlier designs. Further, the epitopes predicted were screened against stringent criteria to ensure selection of a potent candidate with maximum antigen coverage and best immune response. The vaccine dose-based immune response simulation studies revealed a rapid antigen clearance through antibody generation and elevated levels of cell-mediated immunity during repeated exposure of the vaccine. The favourable results of the analysis strongly indicate that the vaccine construct is indeed a potent vaccine candidate and ready to proceed to the next steps of experimental validation and efficacy studies.Supplementary informationThe online version contains supplementary material available at 10.1007/s13205-020-02574-x.

Dataset Information

Designing of Peptide Based Multi-Epitope Vaccine Construct against Gallbladder Cancer Using Immunoinformatics and Computational Approaches.

Publications

Designing of Peptide Based Multi-Epitope Vaccine Construct against Gallbladder Cancer Using Immunoinformatics and Computational Approaches.

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