Design of a Novel Multi-Epitope Vaccine Against Echinococcus granulosus in Immunoinformatics.
Ontology highlight
ABSTRACT:
SUBMITTER: Yu M
PROVIDER: S-EPMC8388843 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Marburg virus (MARV) is a highly contagious and virulent agent belonging to Filoviridae family. MARV causes severe hemorrhagic fever in humans and non-human primates. Owing to its highly virulent nature, preventive approaches are promising for its control. There is currently no approved drug or vaccine against MARV, and management mainly involves supportive care to treat symptoms and prevent complications. Our aim was to design a novel multi-epitope vaccine (MEV) against MARV using immunoinformatics studies. In this study, various proteins (VP35, VP40 and glycoprotein precursor) were used and potential epitopes were selected. CTL and HTL epitopes covered 79.44% and 70.55% of the global population, respectively. The designed MEV construct was stable and expressed in Escherichia coli (E. coli) host. The physicochemical properties were also acceptable. MARV MEV candidate could predict comprehensive immune responses such as those of humoral and cellular in silico. Additionally, efficient interaction to toll-like receptor 3 (TLR3) and its agonist (β-defensin) was predicted. There is a need for validation of these results using further in vitro and in vivo studies.
| S-EPMC11227231 | biostudies-literature
Project description:Helicobacter pylori (H. pylori) is a gram-negative spiral bacterium that caused infections in half of the world's population and had been identified as type I carcinogen by the World Health Organization. Compared with antibiotic treatment which could result in drug resistance, the vaccine therapy is becoming a promising immunotherapy option against H. pylori. Further, the multi-epitope vaccine could provoke a wider immune protection to control H. pylori infection. In this study, the in-silico immunogenicity calculations on 381 protein sequences of H. pylori were performed, and the immunogenicity of selected proteins with top-ranked score were tested. The B cell epitopes and T cell epitopes from three well performed proteins UreB, PLA1, and Omp6 were assembled into six constructs of multi-epitope vaccines with random orders. In order to select the optimal constructs, the stability of the vaccine structure and the exposure of B cell epitopes on the vaccine surface were evaluated based on structure prediction and solvent accessible surface area analysis. Finally Construct S1 was selected and molecular docking showed that it had the potential of binding TLR2, TLR4, and TLR9 to stimulate strong immune response. In particular, this study provides good suggestions for epitope assembly in the construction of multi-epitope vaccines and it may be helpful to control H. pylori infection in the future.Supplementary informationThe online version of this article (10.1007/s10989-020-10148-x) contains supplementary material, which is available to authorized users.
| S-EPMC7778422 | biostudies-literature
Project description:Cervical cancer, caused by human papillomavirus (HPV), is the fourth most common type of cancer among women worldwide. While HPV prophylactic vaccines are available, they have no therapeutic effects and do not clear up existing infections. This study aims to design a therapeutic vaccine against cervical cancer using reverse vaccinology. In this study, the E6 and E7 oncoproteins from HPV16 were chosen as the target antigens for epitope prediction. Cytotoxic T lymphocytes (CTL) and helper T lymphocytes (HTL) epitopes were predicted, and the best epitopes were selected based on antigenicity, allergenicity, and toxicity. The final vaccine construct was composed of the selected epitopes, along with the appropriate adjuvant and linkers. The multi-epitope vaccine was evaluated in terms of physicochemical properties, antigenicity, and allergenicity. The tertiary structure of the vaccine construct was predicted. Furthermore, several analyses were also carried out, including molecular docking, molecular dynamics (MD) simulation, and in silico cloning of the vaccine construct. The results showed that the final proposed vaccine could be considered an effective therapeutic vaccine for HPV; however, in vitro and in vivo experiments are required to validate the efficacy of this vaccine candidate.
| S-EPMC8196015 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 disease in China. So far, no vaccine has licensed to protect against infection with COVID-19, therefore an effective COVID-19 vaccine needed. The aim of this study was to predict antigenic peptides of SARS-CoV-2 for designing the COVID-19 vaccine using immunoinformatic analysis. In this study, T and B-cell epitopes of S protein were predicted and screened based on the antigenicity, toxicity, allergenicity, and cross-reactivity with human proteomes. The epitopes were joined by the appropriate linker. LT-IIc as an adjuvant was attached to the end of the structure. The secondary and 3D structure of the vaccine was predicted. The refinement process was performed to improve the quality of the 3D model structure; the validation process is performed using the Ramachandran plot and ProSA z-score. The proposed vaccine's binding affinity to the HLA-A11:01 and HLA-DRB1_01:01 molecule was evaluated by molecular docking. Using molecular dynamics, the stability of vaccine-HLA complexes was also evaluated. Finally, in silico gene cloning was performed in the pET30a (+) vector. The findings suggest that the current vaccine may be a promising vaccine to prevent SARS-CoV-2 infection.
| S-EPMC7362859 | biostudies-literature
Project description:Bovine ephemeral fever virus (BEFV) is an overlooked pathogen, recently gaining widespread attention owing to its associated enormous economic impacts affecting the global livestock industries. High endemicity with rapid spread and morbidity greatly impacts bovine species, demanding adequate attention towards BEFV prophylaxis. Currently, a few suboptimum vaccines are prevailing, but were confined to local strains with limited protection. Therefore, we designed a highly efficacious multi-epitope vaccine candidate targeted against the geographically distributed BEFV population. By utilizing immunoinformatics technology, all structural proteins were targeted for B- and T-cell epitope prediction against the entire allele population of BoLA molecules. Prioritized epitopes were adjoined by linkers and adjuvants to effectively induce both cellular and humoral immune responses in bovine. Subsequently, the in silico construct was characterized for its physicochemical parameters, high immunogenicity, least allergenicity, and non-toxicity. The 3D modeling, refinement, and validation of ligand (vaccine construct) and receptor (bovine TLR7) then followed molecular docking and molecular dynamic simulation to validate their stable interactions. Moreover, in silico cloning of codon-optimized vaccine construct in the prokaryotic expression vector (pET28a) was explored. This is the first time HTL epitopes have been predicted using bovine datasets. We anticipate that the designed construct could be an effective prophylactic remedy for the BEF disease that may pave the way for future laboratory experiments.
| S-EPMC8402647 | biostudies-literature
Project description:BackgroundVisceral Leishmaniasis (VL) is a fatal vector-borne parasitic disorder occurring mainly in tropical and subtropical regions. VL falls under the category of neglected tropical diseases with growing drug resistance and lacking a licensed vaccine. Conventional vaccine synthesis techniques are often very laborious and challenging. With the advancement of bioinformatics and its application in immunology, it is now more convenient to design multi-epitope vaccines comprising predicted immuno-dominant epitopes of multiple antigenic proteins. We have chosen four antigenic proteins of Leishmania donovani and identified their T-cell and B-cell epitopes, utilizing those for in-silico chimeric vaccine designing. The various physicochemical characteristics of the vaccine have been explored and the tertiary structure of the chimeric construct is predicted to perform docking studies and molecular dynamics simulations.ResultsThe vaccine construct is generated by joining the epitopes with specific linkers. The predicted tertiary structure of the vaccine has been found to be valid and docking studies reveal the construct shows a high affinity towards the TLR-4 receptor. Population coverage analysis shows the vaccine can be effective on the majority of the world population. In-silico immune simulation studies confirms the vaccine to raise a pro-inflammatory response with the proliferation of activated T and B cells. In-silico codon optimization and cloning of the vaccine nucleic acid sequence have also been achieved in the pET28a vector.ConclusionThe above bioinformatics data support that the construct may act as a potential vaccine. Further wet lab synthesis of the vaccine and in vivo works has to be undertaken in animal model to confirm vaccine potency.
| S-EPMC9354309 | biostudies-literature
Project description:In the current era, our experience is full of pandemic infectious agents that no longer threaten the major local source but the whole globe. One such infectious agent is HPV, a sexually transmitted disease that can cause various clinical disorders, including benign lesions and cervical cancer. Since available vaccines still need further improvements in order to enhance efficacy, our goal was to design a chimeric vaccine against HPV using an immunoinformatics approach. For designing the vaccine, the sequence of HPV was retrieved, and then phylogenetic analysis was performed. Several CTL epitopes, HTL epitopes, and LBL epitopes were all predicted using bioinformatics tools. After checking the antigenicity, allergenicity, and toxicity scores, the best epitopes were selected for vaccine construction, and then physicochemical and immunological properties were analyzed. Subsequently, vaccine 3D structure prediction, refinement, and validation were performed. Molecular docking and dynamics simulation techniques were used to explore the interactions between the Toll-like receptor 2 and the modeled vaccine construct. To ensure the vaccine protein was expressed at a higher level, the construct was computationally cloned into the pET28a (+) plasmid. The molecular docking and simulation results showed that our designed vaccine is stable, of immunogenic quality, and has considerable solubility. Through in silico immune simulation, it was predicted that the designed polypeptide vaccine construct would trigger both humoral and cellular immune responses. The developed vaccine showed significant affinity for the TLR2 receptor molecule. However, additional laboratory research is required to evaluate its safety and efficacy.
| S-EPMC10216030 | biostudies-literature
Project description:Dengue poses a global health threat, which will persist without therapeutic intervention. Immunity induced by exposure to one serotype does not confer long-term protection against secondary infection with other serotypes and is potentially capable of enhancing this infection. Although vaccination is believed to induce durable and protective responses against all the dengue virus (DENV) serotypes in order to reduce the burden posed by this virus, the development of a safe and efficacious vaccine remains a challenge. Immunoinformatics and computational vaccinology have been utilized in studies of infectious diseases to provide insight into the host-pathogen interactions thus justifying their use in vaccine development. Since vaccination is the best bet to reduce the burden posed by DENV, this study is aimed at developing a multi-epitope based vaccines for dengue control. Combined approaches of reverse vaccinology and immunoinformatics were utilized to design multi-epitope based vaccine from the sequence of DENV. Specifically, BCPreds and IEDB servers were used to predict the B-cell and T-cell epitopes, respectively. Molecular docking was carried out using Schrödinger, PATCHDOCK and FIREDOCK. Codon optimization and in silico cloning were done using JCAT and SnapGene respectively. Finally, the efficiency and stability of the designed vaccines were assessed by an in silico immune simulation and molecular dynamic simulation, respectively. The predicted epitopes were prioritized using in-house criteria. Four candidate vaccines (DV-1-4) were designed using suitable adjuvant and linkers in addition to the shortlisted epitopes. The binding interactions of these vaccines against the receptors TLR-2, TLR-4, MHC-1 and MHC-2 show that these candidate vaccines perfectly fit into the binding domains of the receptors. In addition, DV-1 has a better binding energies of - 60.07, - 63.40, - 69.89 kcal/mol against MHC-1, TLR-2, and TLR-4, with respect to the other vaccines. All the designed vaccines were highly antigenic, soluble, non-allergenic, non-toxic, flexible, and topologically assessable. The immune simulation analysis showed that DV-1 may elicit specific immune response against dengue virus. Moreover, codon optimization and in silico cloning validated the expressions of all the designed vaccines in E. coli. Finally, the molecular dynamic study shows that DV-1 is stable with minimum RMSF against TLR4. Immunoinformatics tools are now applied to screen genomes of interest for possible vaccine target. The designed vaccine candidates may be further experimentally investigated as potential vaccines capable of providing definitive preventive measure against dengue virus infection.
| S-EPMC8492693 | biostudies-literature
Project description:Acinetobacter baumannii is one of the most successful pathogens causing nosocomial infections and has significantly multidrug-resistant. So far, there are no certain treatments to protect against infection with A. baumannii, therefore an effective A. baumannii vaccine needed. The purpose of this study was to predict antigenic epitopes of CarO protein for designing the A. baumannii vaccine using immunoinformatics analysis. CarO protein is one of the most important factors in the resistance against the antibiotic Carbapenem. In this study, T and B-cell epitopes of CarO protein were predicted and screened based on the antigenicity, toxicity, allergenicity features. The epitopes were linked by suitable linkers. Four different adjuvants were attached to the vaccine constructs which among them, vaccine construct 3 was chosen to predict the secondary and the 3D structure of the vaccine. The refinement process was performed to improve the quality of the 3D model structure; the validation process is performed using the Ramachandran plot and ProSA z-score. The designed vaccine's binding affinity to six various HLA molecules and TLR 2 and TLR4 were evaluated by molecular docking. Finally, in silico gene cloning was performed in the pET28a (+) vector. The findings suggest that the vaccine may be a promising vaccine to prevent A. baumannii infection.
| S-EPMC8397861 | biostudies-literature
Project description:Klebsiella pneumoniae is an opportunistic gram-negative bacterium that causes nosocomial infection in healthcare settings. Despite the high morbidity and mortality rate associated with these bacterial infections, no effective vaccine is available to counter the pathogen. In this study, the pangenome of a total of 222 available complete genomes of K. pneumoniae was explored to obtain the core proteome. A reverse vaccinology strategy was applied to the core proteins to identify four antigenic proteins. These proteins were then subjected to epitope mapping and prioritization steps to shortlist nine B-cell derived T-cell epitopes which were linked together using GPGPG linkers. An adjuvant (Cholera Toxin B) was also added at the N-terminal of the vaccine construct to improve its immunogenicity and a stabilized multi-epitope protein structure was obtained using molecular dynamics simulation. The designed vaccine exhibited sustainable and strong bonding interactions with Toll-like receptor 2 and Toll-like receptor 4. In silico reverse translation and codon optimization also confirmed its high expression in E. coli K12 strain. The computer-aided analyses performed in this study imply that the designed multi-epitope vaccine can elicit specific immune responses against K. pneumoniae. However, wet lab validation is necessary to further verify the effectiveness of this proposed vaccine candidate.
| S-EPMC6789656 | biostudies-literature