A Computational Reverse Vaccinology Approach for the Design and Development of Multi-Epitopic Vaccine Against Avian Pathogen Mycoplasma gallisepticum
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ABSTRACT:
SUBMITTER: Mugunthan S
PROVIDER: S-EPMC8577832 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundReverse vaccinology accelerates the discovery of potential vaccine candidates (PVCs) prior to experimental validation. Current programs typically use one bacterial proteome to identify PVCs through a filtering architecture using feature prediction programs or a machine learning approach. Filtering approaches may eliminate potential antigens based on limitations in the accuracy of prediction tools used. Machine learning approaches are heavily dependent on the selection of training datasets with experimentally validated antigens (positive control) and non-protective-antigens (negative control). The use of one or few bacterial proteomes does not assess PVC conservation among strains, an important feature of vaccine antigens.ResultsWe present ReVac, which implements both a panoply of feature prediction programs without filtering out proteins, and scoring of candidates based on predictions made on curated positive and negative control PVCs datasets. ReVac surveys several genomes assessing protein conservation, as well as DNA and protein repeats, which may result in variable expression of PVCs. ReVac's orthologous clustering of conserved genes, identifies core and dispensable genome components. This is useful for determining the degree of conservation of PVCs among the population of isolates for a given pathogen. Potential vaccine candidates are then prioritized based on conservation and overall feature-based scoring. We present the application of ReVac, applied to 69 Moraxella catarrhalis and 270 non-typeable Haemophilus influenzae genomes, prioritizing 64 and 29 proteins as PVCs, respectively.ConclusionReVac's use of a scoring scheme ranks PVCs for subsequent experimental testing. It employs a redundancy-based approach in its predictions of features using several prediction tools. The protein's features are collated, and each protein is ranked based on the scoring scheme. Multi-genome analyses performed in ReVac allow for a comprehensive overview of PVCs from a pan-genome perspective, as an essential pre-requisite for any bacterial subunit vaccine design. ReVac prioritized PVCs of two human respiratory pathogens, identifying both novel and previously validated PVCs.
| S-EPMC6916091 | biostudies-literature
Project description:Mycobacteroides abscessus (Previously Mycobacterium abscessus) is an emerging microorganism of the newly defined genera Mycobacteroides that causes mainly skin and tissue diseases in humans. The recent availability of total 34 fully sequenced genomes of different strains belonging to this species has provided an opportunity to utilize this genomics data to gain novel insights and guide the development of specific antimicrobial therapies. In the present study, we collected collectively 34 complete genome sequences of M. abscessus from the NCBI GenBank database. Pangenome analysis was conducted on these genomes to understand the genetic diversity and to obtain proteins associated with its core genome. These core proteins were then subjected to various subtractive filters to identify potential antigenic targets that were subjected to multi-epitope vaccine design. Our analysis projected the open pangenome of M. abscessus containing 3443 core genes. After applying various stepwise filtration steps on the core proteins, a total of four potential antigenic targets were identified. Utilizing their constituent CD4 and CD8 T-cell epitopes, a multi-epitope based subunit vaccine was computationally designed. Sequence-based analysis as well as structural characterization revealed the immunological effectiveness of this designed vaccine. Further molecular docking, molecular dynamics simulation and binding free energy estimation with Toll-like receptor 2 indicated strong structural associations of the vaccine with the immune receptor. The promising results are encouraging and need to be validated by additional wet laboratory studies for confirmation.
| S-EPMC8159972 | biostudies-literature
Project description:Outbreaks of monkeypox virus infections have imposed major health concerns worldwide, with high morbidity threats to children and immunocompromised adults. Although repurposed drugs and vaccines are being used to curb the disease, the evolving traits of the virus, exhibiting considerable genetic dynamicity, challenge the limits of a targeted treatment. A pan-genome-based reverse vaccinology approach can provide fast and efficient solutions to resolve persistent inconveniences in experimental vaccine design during an outbreak-exigency. The approach encompassed screening of available monkeypox whole genomes (n = 910) to identify viral targets. From 102 screened viral targets, viral proteins L5L, A28, and L5 were finalized based on their location, solubility, and antigenicity. The potential T-cell and B-cell epitopes were extracted from the proteins using immunoinformatics tools and algorithms. Multiple vaccine constructs were designed by combining the epitopes. Based on immunological properties, chemical stability, and structural quality, a novel multi-epitopic vaccine construct, V4, was finalized. Flexible-docking and coarse-dynamics simulation portrayed that the V4 had high binding affinity towards human HLA-proteins (binding energy < -15.0 kcal/mol) with low conformational fluctuations (<1 Å). Thus, the vaccine construct (V4) may act as an efficient vaccine to induce immunity against monkeypox, which encourages experimental validation and similar approaches against emerging viral infections.
| S-EPMC9695528 | biostudies-literature
Project description:Mycoplasma gallisepticum causes chronic respiratory disease in chickens leading to large economic losses in the poultry industry, and the impacts remain to be a great challenge for a longer period. Among the other approaches, a vaccine targeting the adhesion proteins of M. gallisepticum would be a promising candidate in controlling the infection. Thus, the present study is aimed to design a multi-epitope vaccine candidate using cytoadhesion proteins of M. gallisepticum through an advanced immunoinformatics approach. As a result, the multi-epitope vaccine was constructed, which comprised potential T-cell and B-cell binding epitopes with appropriate adjuvants. The designed multi-epitope vaccine represented high antigenicity with viable physiochemical properties. The prospective three-dimensional structure of the epitope was predicted, refined, and validated. The molecular docking analysis of multi-epitope vaccine candidates with the chicken Toll-like receptor-5 predicted effective binding. Furthermore, codon optimization and in silico cloning ensured high expression. Thus, the present finding indicates that the engineered multi-epitope vaccine is structurally stable and can induce a strong immune response. Furthermore, the multi-epitope vaccine is suggested to be a suitable vaccine candidate for the M. gallisepticum infection due to its effective binding capacity and precise specificity.
| S-EPMC8173551 | biostudies-literature
Project description:Ebola virus (EBOV) is a dangerous zoonotic infectious disease. To date, more than 25 EBOV outbreaks have been documented, the majority of which have occurred in Central Africa. The rVSVG-ZEBOV-GP vaccine (ERVEBO), a live attenuated vaccine, has been approved by the US Food and Drug Administration (FDA) to combat EBOV. Because of the several drawbacks of live attenuated vaccines, multi-epitope vaccines probably appear to be safer than live attenuated vaccines. In this work, we employed immunoinformatics tools to design a multi-epitope vaccine against EBOV. We collected sequences of VP35, VP24, VP30, VP40, GP, and NP proteins from the NCBI database. T-cell and linear B-cell epitopes from target proteins were identified and tested for antigenicity, toxicity, allergenicity, and conservancy. The selected epitopes were then linked together in the vaccine's primary structure using appropriate linkers, and the 50S ribosomal L7/L12 (Locus RL7 MYCTU) sequence was added as an adjuvant to the vaccine construct's N-terminal. The physicochemical, antigenicity, and allergenicity parameters of the vaccine were all found to be satisfactory. The 3D model of the vaccine was predicted, refined, and validated. The vaccine construct had a stable and strong interaction with toll-like receptor 4 (TLR4) based on molecular docking and molecular dynamic simulation (MD) analysis. The results of codon optimization and in silico cloning revealed that the proposed vaccine was highly expressed in Escherichia coli (E. coli). The findings of this study are promising; however, experimental validations should be carried out to confirm these findings.
| S-EPMC9094136 | biostudies-literature
Project description:Japanese encephalitis (JE) is a serious leading health complication emerging expansively that has severely affected the survival rate of human beings. This fatal disease is caused by JE Virus (JEV). The current study was carried out for designing a multi-epitope loaded peptide vaccine to prevent JEV. Based on reverse vaccinology and in silico approaches, octapeptide B-cell and hexapeptide T-cell epitopes belonging to five proteins, viz. E, prM, NS1, NS3 and NS5 of JEV were determined. Hydrophilicity, antigenicity, immunogenicity and aliphatic amino acids of the epitopes were estimated. Further, the epitopes were analyzed for different physicochemical parameters, e.g. total net charges, amino acid composition and Boman index. Out of all the epitopes, a total of four T-cell epitopes namely KRADSS, KRSRRS, SKRSRR and KECPDE and one B-cell epitope i.e. PKPCSKGD were found to have potential for raising immunity in human against the pathogen. Taking into account the outcome of this study, the pharmaceutical industries could initiate efforts to combine the identified epitopes together with adjuvant or carrier protein to develop a multi-epitope-loaded peptide vaccine against JEV. The peptide vaccine, being cost effective, could be administered as a prophylactic measure and in JEV infected individuals to combat the spread of this virus in human population. However, prior to administration into human beings, the vaccine must pass through several clinical trials.
| S-EPMC7106040 | biostudies-literature
Project description:Respiratory pathogens are a health threat for poultry. Co-infections lead to the exacerbation of clinical symptoms and lesions. Mycoplasma gallisepticum (M. gallispeticum) and Avian Metapneumovirus (AMPV) are two avian respiratory pathogens that co-circulate worldwide. The knowledge about the host-pathogen interaction of M. gallispeticum and AMPV in the chicken respiratory tract is limited. We aimed to investigate how co-infections affect the pathogenesis of the respiratory disease and whether the order of invading pathogens leads to changes in host-pathogen interaction. We used chicken tracheal organ cultures (TOC) to investigate pathogen invasion and replication, lesion development, and selected innate immune responses, such as interferon (IFN) α, inducible nitric oxide synthase (iNOS) and IFNλ mRNA expression levels. We performed mono-inoculations (AMPV or M. gallispeticum) or dual-inoculations in two orders with a 24-h interval between the first and second pathogen. Dual-inoculations compared to mono-inoculations resulted in more severe host reactions. Pre-infection with AMPV followed by M. gallispeticum resulted in prolonged viral replication, more significant innate immune responses, and lesions (p < 0.05). AMPV as the secondary pathogen impaired the bacterial attachment process. Consequently, the M. gallispeticum replication was delayed, the innate immune response was less pronounced, and lesions appeared later. Our results suggest a competing process in co-infections and offer new insights in disease processes.
| S-EPMC8618481 | biostudies-literature
Project description:Genomic content of Vaccine strains were probed against the known sequence of the virulent strain Rlow of M. gallisepticum to identify divergent or absent genes in the attenuated strains.
2009-12-24 | GSE19629 | GEO
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.
| S-EPMC9275536 | biostudies-literature
Project description:Antibiotic resistance is a major public health concern that has resulted in high healthcare costs, increased mortality, and the emergence of novel bacterial diseases. Cardiobacterium valvarum, an antibiotic-resistant bacterium, is one of the leading causes of heart disease. Currently, there is no licensed vaccination against C. valvarum. In this research, an in silico-based vaccine was designed against C. valvarum using reverse vaccinology, bioinformatics, and immunoinformatics techniques. 4206 core proteins, 2027 nonredundant proteins, and 2179 redundant proteins were predicted. Among nonredundant proteins, 23 proteins were predicted in an extracellular membrane, 30 in the outer membrane, and 62 in the periplasmic membrane region. After applying several subtractive proteomics filters, two proteins, TonB-dependent siderophore receptor and hypothetical protein, were chosen for epitope prediction. In the epitope selection phase, B and T-cellepitopes were analyzed and shortlisted for vaccine design. The vaccine model was designed by linking selected epitopes with GPGPG linkers to avoid flexibility. Furthermore, the vaccine model was linked to cholera toxin B adjuvant to induce a proper immune response. The docking approach was utilized to analyze binding affinity to immune cell receptors. Molecular docking results predicted 12.75 kcal/mol for a Vaccine with MHC-I, 6.89 for a vaccine with MHC-II, and 19.51 vaccine with TLR-4. The MMGBSA estimated -94, -78, and -76 kcal/mol for TLR-4 and vaccine, MHC-I and vaccine, and MHC-II and vaccine, while the MMPBSA analysis estimated -97, -61, and -72 kcal/mol for TLR-4 with the vaccine, MHC-I with vaccine, and MHC-II with a vaccine. Molecular dynamic simulation analysis revealed that the designed vaccine construct has proper stability with immune cell receptors as it is essential for inducing an immune response. In conclusion, we observed that the model vaccine candidate has the potency to induce an immune response in the host. However, the study is designed purely on a computational basis; hence, experimental validation is strongly recommended.
| S-EPMC10322295 | biostudies-literature