Subtractive Proteomics Analysis Revealed Lipid A-4’phosphatase (lpxF) as a Potential Candidate for Epitope-based Vaccine Design Against Helicobacter pylori Infection (original) (raw)
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Scientific Reports, 2019
Helicobacter Pylori is a known causal agent of gastric malignancies and peptic ulcers. The extremophile nature of this bacterium is protecting it from designing a potent drug against it. Therefore, the use of computational approaches to design antigenic, stable and safe vaccine against this pathogen could help to control the infections associated with it. Therefore, in this study, we used multiple immunoinformatics approaches along with other computational approaches to design a multi-epitopes subunit vaccine against H. Pylori. A total of 7 CTL and 12 HTL antigenic epitopes based on c-terminal cleavage and MHC binding scores were predicted from the four selected proteins (CagA, OipA, GroEL and cagA). The predicted epitopes were joined by AYY and GPGPG linkers. Β-defensins adjuvant was added to the N-terminus of the vaccine. For validation, immunogenicity, allergenicity and physiochemical analysis were conducted. The designed vaccine is likely antigenic in nature and produced robust ...
Microbial Pathogenesis, 2018
Gastric cancer risk and adverse ramifications by augmented multi-drug resistance (MDR) of Helicobacter pylori are alarming serious health concern. Combating through available drugs is a difficult task due to lack of appropriate common targets against genetically diverse strains. To improve efficacy, the effective targets should be identified and critically assessed. In the present study, we aim to predict the potential novel targets against H. pylori strains by employing computer aided approach. The genomic dataset of 53 H. pylori strains was comparatively processed and eventually predicted 826 'conserved gene products'. Further, we performed subtractive genomic approach in search of promising crucial targets through the combination of in silico analyses. Codon adaptation index (CAI) value calculation and literature surveys were also done in order to find highly expressed gene products with novelty. Consequently, four enzymes and three membrane proteins were prioritized as new therapeutic and vaccine targets respectively which found to have more interactors in network with high-confidence score, druggability, antigenicity and molecular weight <110 kDa. Therefore, our results underpin the importance of new targets may counteract with false-positive / negatives and facilitate appropriate potential targets for a new insight of reliable therapeutic development.
Epitope-driven common subunit vaccine design against H. pylori strains
Journal of Biomolecular Structure and Dynamics, 2018
The developing potent vaccine is a pre-emptive strategy to tackle drug abuses and maladies of multidrug-resistant Helicobacter pylori strains. Ongoing vaccine studies are being conducted, however, development is in its infancy as ineffective vaccine targets might be. So, the linear perspective may indicate the need for potent subunit vaccine variants. Here, surface-exposed membrane proteins out of 826 common proteins of 53 H. pylori strains were chosen for analysis, as a follow-up to previous studies; these proteins are responsible for antigenicity to elicit the immune response. Antigenic determinant regions on prognostic targets were evaluated in the successive peptide screening using experimental T-cell epitope positive control and optimized with eminent immunoinformatics algorithms. In the milieu of docking, an ensemble of 2200 multiple conformers of complexes of modeled peptide and human leukocyte antigen-antigenD Related Beta-chain (HLA-DRB) was generated. Prioritized physics-based Molecular Mechanics-Generalized Born Surface Area approach coupled with bond length monitoring paved the improvement of prediction accuracy with binding potency estimations. DG bind free energy, interaction patterns, enrichment factor contributions and root-mean-square deviation predictions evidenced the existence of better binding affinities of four novel peptides hits with predominant allotype HLA-DR alleles than co-crystal controls. Moreover, conformational plasticity and stability assessments of the better ranked complex epitope-2 (86-FRRNPNINV-94)-HLA-DRB5 Ã 0101 formulated in dynamic simulations of 10,416 trajectories depicted stable interaction profile that correlated with docking endpoints. Thus, the proposed novel vaccine cocktails of the study would be ideal candidates and provide new insights for T-cell driven subunit vaccine design against H. pylori strains ARTICLE HISTORY
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2015
Helicobacter pylori (H. pylori) is an important pathogen associated with diverse gastric disorders ranging from peptic ulcer to malignancy. It has also been recognized by the World Health Organization (WHO) as class I carcinogen. Conventional treatment regimens for H. pylori seem to be ineffective, possibly due to antibiotic resistance mechanisms acquired by the pathogen. In this study we have successfully employed a reverse vaccinology approach to predict the potential vaccine candidates against H. pylori. The predicted potential vaccine candidates include vacA, babA, sabA, fecA and omp16. Host-pathogen interactions analysis elaborated their direct or indirect role in the specific signaling pathways including epithelial cell polarity, metabolism, secretion system and transport. Furthermore, surface-exposed antigenic epitopes were predicted and analyzed for conservation among 39 complete genomes of H. pylori (Genbank) for all the candidate proteins. These epitopes may serve as a bas...
Prediction of Epitopes in the Proteome of Helicobacter pylori
Global Journal of Health Science, 2018
Helicobacter pylori (H. pylori) is classified by the World Health Organization (WHO) as a group I carcinogen and is one of the most efficient human pathogens with over half of the world's population colonized by this gram-negative spiral bacterium. H. pylori can cause a chronic infection in the stomach during early childhood that persists throughout life due to diverse mechanisms of immune response evasion. H. pylori has several factors strongly associated with increased risk of disease such as toxins, adhesins, and chemoattractants, some of which are highly polymorphic, phase variable, and have different functions. Conventional treatments involve the use of antibiotics. However, treatment frequently fails due to the resistance H. pylori has progressively developed to antibiotics. This creates the need for different treatments made possible by identifying new therapeutic targets in the pathogen's genome. The purpose of this study was an in silico prediction of T-and B-epitopes in H. pylori proteins. Twenty-two external membrane proteins from H. pylori Strain 26695 (accession number NC_000915) were identified using the web tool Vaxign (http://www.violinet.org/vaxign/). A total of one-hundred epitopes (60 class I epitopes and 40 class II epitopes) that could be used to develop novel non-antibiotics drugs for an H. pylori infection were predicted.
2020
Helicobacter pylori infection and its treatment still remain a challenge for human health worldwide. A variety of antibiotics and combination therapies are currently used to treat H. pylori induced ulcers and carcinoma; however, no effective treatment is available to eliminate the pathogen from the body. Additionally, antibiotic resistance is also one of the main reasons for prolonged and persistent infection. Until new drugs are available for this infection, vaccinology seems the only alternative opportunity to exploit against H. pylori induced diseases. Multiple epitopes prioritized in our previous study have been tested for their possible antigenic combinations, resulting in 169-mer and 183-mer peptide vaccines containing the amino acid sequences of 3 and 4 epitopes respectively, along with adjuvant (Cholera Toxin Subunit B adjuvant at 5’ end) and linkers (GPGPG and EAAAK). Poly-epitope proteins proposed as potential vaccine candidates against H. pylori include SabA-HP0289-Omp16-...
An Integrated Genomic and Immunoinformatic Approach to H. pylori Vaccine Design
Immunome research, 2011
One useful application of pattern matching algorithms is identification of major histocompatability complex (MHC) ligands and T-cell epitopes. Peptides that bind to MHC molecules and interact with T cell receptors to stimulate the immune system are critical antigens for protection against infectious pathogens. We describe a genomes-to-vaccine approach to H. pylori vaccine design that takes advantage of immunoinformatics algorithms to rapidly identify T-cell epitope sequences from large genomic datasets. To design a globally relevant vaccine, we used computational methods to identify a core genome comprised of 676 open reading frames (ORFs) from amongst seven genetically and phenotypically diverse H. pylori strains from around the world. Of the 1,241,153 9-mer sequences encoded by these ORFs, 106,791 were identical amongst all seven genomes and 23,654 scored in the top 5% of predicted HLA ligands for at least one of eight archetypal Class II HLA alleles when evaluated by EpiMatrix. T...
Bioinformation, 2019
Helicobacter pylori, a unique gastric pathogen causing chronic inflammation in the gastric mucosa with a possibility to develop gastric cancer has one-third of its proteins still uncharacterized. In this study, a hypothetical protein (HP) namely HPAG1_0576 from H. pylori HPAG1 was chosen for detailed computational analysis of its structural, functional and epitopic properties. The primary, secondary and 3D structure/model of the selected HP was constructed. Then refinement and structure validation were done, which indicated a good quality of the newly constructed model. ProFunc and STRING suggested that HPAG1_0576 shares 98% identity with a carcinogenic factor, TNF-α inducing protein (Tip-α) of H. pylori. IEDB immunoinformatics tool predicted VLMLQACTCPNTSQRNS from position 19-35 as most potential B-cell linear epitope and SFLKSKQL from position 5-12 as most potent conformational epitope. Alternatively, FALVRARGF and FLCGLGVLM were predicted as most immunogenic CD8+ and CD4+ T-cell epitopes respectively. At the same time findings of IFN epitope tool suggests that, HPAG1_0576 had a great potential to evoke interferon-gamma (IFN-γ) mediated immune response. However, this experiment is a primary approach for in silico vaccine designing from a HP, findings of this study will provide significant insights in further investigations and will assist in identifying new drug targets/vaccine candidates.
International Journal of Peptide Research and Therapeutics
Helicobacter pylori is a highly potential pathogen to colonize in the human stomach. This bacterial strain is now alarming serious health concern all over the world. Combating through available drugs is a difficult task due to lack of appropriate common targets against genetically diverse strains. Therefore, the developments of effective targets vaccines require alternative strategies to eliminate the H. pylori infection. In this study, we developed a novel vaccine construct using B-cell derived T-cell epitopes from four target antigenic proteins (HpaA, FlaA, FlaB and Omp18), and found the induction of possible immune response using advanced immunoinformatics approaches. In order to boost immune system, we tagged adjuvant (50S ribosomal protein L7/L12) with a suitable linker at the N-terminus side of vaccine sequence. Protein-protein docking between human Toll like receptor 5 (TLR5) and vaccine construct help to predict the way of inductive signaling that leads to immune-response. The calculated negative score (− 151.4, + / − 8.7) of molecular docking complex signify the best binding interface. Molecular dynamics simulation studies confirmed the proper docking between TLR5 and vaccine candidate. Moreover, Normal mode analysis (NMA) calculates the molecular motion of the docking complex. The low eigenvalue (2.935e −05) indicates the stable and flexible molecular motion in the binding interaction side. Finally, in-silico cloning of vaccine candidate was performed using expression vector pET28b (+) with the optimized restriction sites.
In silico identification of potential therapeutic targets in the human pathogen Helicobacter pylori
In silico biology, 2006
Availability of genome sequences of pathogens has provided a tremendous amount of information that can be useful in drug target and vaccine target identification. One of the recently adopted strategies is based on a subtractive genomics approach, in which the subtraction dataset between the host and pathogen genome provides information for a set of genes that are likely to be essential to the pathogen but absent in the host. This approach has been used successfully in recent times to identify essential genes in Pseudomonas aeruginosa. We have used the same methodology to analyse the whole genome sequence of the human gastric pathogen Helicobacter pylori. Our analysis revealed that out of the 1590 coding sequences of the pathogen, 40 represent essential genes that have no human homolog. We have further analysed these 40 genes by the protein sequence databases to list some 10 genes whose products are possibly exposed on the pathogen surface. This preliminary work reported here identif...