Vacceed: a high-throughput in silico vaccine candidate discovery pipeline for eukaryotic pathogens based on reverse vaccinology.
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ABSTRACT:
SUBMITTER: Goodswen SJ
PROVIDER: S-EPMC4207429 | biostudies-other | 2014 Aug
REPOSITORIES: biostudies-other
Publications
Vacceed: a high-throughput in silico vaccine candidate discovery pipeline for eukaryotic pathogens based on reverse vaccinology.
Goodswen Stephen J SJ Kennedy Paul J PJ Ellis John T JT
Bioinformatics (Oxford, England) 20140429 16
<h4>Unlabelled</h4>We present Vacceed, a highly configurable and scalable framework designed to automate the process of high-throughput in silico vaccine candidate discovery for eukaryotic pathogens. Given thousands of protein sequences from the target pathogen as input, the main output is a ranked list of protein candidates determined by a set of machine learning algorithms. Vacceed has the potential to save time and money by reducing the number of false candidates allocated for laboratory vali ...[more]
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Project description:Background: The novel severe acute respiratory syndrome related corona virus-2 (SARS-CoV-2) belongs to the "Coronaviridae" family and order "Nidovirales", which has caused the pandemic coronavirus disease 2019 (COVID-19). SARS-CoV-2 has been spread in more than a 100 countries, and more than a million have lost their lives. Vaccination and immunization could be an effective strategy to combat fatal COVID-19. Methods: For identification of effective vaccine candidate against COVID-19, various immunoinformatics online tools and softwares were used to predict epitopes. Cytotoxic T cell epitopes, helper T cell epitopes, and B cell epitopes from three structural polyproteins (Spike, Membrane, and Nucleocapsid (SMN) based on the binding affinity towards MHC, antigenicity, non-allergenicity, and non-toxicity) were identified for vaccine development. The multiepitope based vaccine was constructed linking two additional adjuvants human beta-defensin-3 and human beta-defensin-2 at N and C terminal, respectively. Results: The constructed vaccine sequence was found to be a good antigen and non-allergen for the human body. The constructed vaccine was docked with the TLR-3 receptor. The docked complex was further taken for molecular dynamics simulations and RMSD was calculated, which showed stable binding of the complex. The codon adaptation index (CAI) of 0.92 and GC content of 55.5% for E. coli (K12 strain) suggested efficient expression of the predicted vaccine. Conclusion: The current study can be helpful in the reduction of time and cost for further experimental validations and could give a valuable contribution against this pandemic.
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Project description:BackgroundBurkholderia pseudomallei is an infectious agent causing severe disease melioidosis resulting in pneumonia, fever, and acute septicemia in humans. B. pseudomallei show resistance to drugs. No such FDA-approved vaccine is available against B. pseudomallei, and treatment is limited to therapy. Therefore, the scientific study was designed to develop a vaccine for B. pseudomallei. The protein sequence of B. pseudomallei was retrieved from NCBI. B-cell and T-cell epitopes were identified and further screened for allergenicity, antigenicity docking, and simulation.ResultsHere, in this study, in silico approach was applied to design a multi-epitope subunit vaccine peptide consisting of linear B-cell and T-cell epitopes of proteins considered to be potential novel vaccine candidates. Peptide epitopes were joined by adjuvant and EAAAK, CPGPG, and AAY linkers. This constructed vaccine was subjected to in silico immune simulations by C-ImmSim. The protein construct was cloned into PET28a (+) vector for expression study in Escherichia coli using SnapGene.ConclusionThe designed multi-epitope vaccine was analyzed for its physicochemical, structural, and immunological characteristics, and it was found to be antigenic, soluble, stable, nonallergenic, and have a high affinity to its target receptor. The immune simulation studies were carried out on the C-ImmSim showing increased production of cellular and humoral responses indicating that the constructed vaccine proved effective and able to provoke humoral and cell-mediated response immune responses. In silico study could be a breakthrough in designing effective vaccines to eradicate B. pseudomallei globally.
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