Dataset Information

Identification of Ixodid Tick-Specific Aquaporin-1 Potential Anti-tick Vaccine Epitopes: An in-silico Analysis.

ABSTRACT: Ticks are arthropod vectors of pathogens of both Veterinary and Public health importance. Acaricide application, which is currently the mainstay of tick control, is hampered by high cost, the need for regular application and a selection of multi-acaricide resistant tick populations. In light of this, future tick control approaches are poised to rely on the integration of rational acaricide application and other methods, such as vaccination. To contribute to systematic research-guided efforts to produce anti-tick vaccines, we carried out an in-silico analysis of tick aquaporin-1 (AQP1) protein in order to identify tick-specific AQP1 peptide motifs that can be used in future peptide anti-tick vaccine development. We carried out multiple sequence alignment (MSA), motif analysis, homology modeling, and structural analysis to identify tick-specific AQP1 peptide motifs. BepiPred, Chou and Fasman-Turn, Karplus and Schulz Flexibility, and Parker-Hydrophilicity prediction models were used to predict these motifs' potential to induce B cell mediated immune responses. The tick AQP1 (GenBankID: QDO67142.1) protein was largely similar to the bovine AQP1 (PDB:1J4N) (23 % sequence similarity; Structural superimposition of the homology model and 14JN homotetramers gave an RMSD = 3.269 while superimposition of a single chain gave an RMSD = 1.475). Tick and bovine AQP1 transmembrane domains were largely similar while their extracellular and cytoplasmic domain loops showed variation. Two tick-specific AQP1 peptide motifs; M7 (residues 106-125, p = 5.4e-25), and M8 (residues 85-104, p = 3.3e-24) were identified. These two motifs are located on the extra-cellular AQP1 domain. Motifs; M7 and M8 showed the highest Parker-Hydrophilicity prediction immunogenicity scores of 1.784 and 1.536, respectively. These two motifs can be a good starting point for the development of potential tick AQP1 peptide-based anti-tick vaccines. Further analyses such as molecular dynamics, in vitro assays, and in vivo immunization assays are required to validate these findings.

SUBMITTER: Ndekezi C

PROVIDER: S-EPMC6775757 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Identification of Ixodid Tick-Specific Aquaporin-1 Potential Anti-tick Vaccine Epitopes: An <i>in-silico</i> Analysis.

Ndekezi Christian C Nkamwesiga Joseph J Ochwo Sylvester S Kimuda Magambo Phillip MP Mwiine Frank Norbert FN Tweyongyere Robert R Amanyire Wilson W Muhanguzi Dennis D

Frontiers in bioengineering and biotechnology 20190926

Ticks are arthropod vectors of pathogens of both Veterinary and Public health importance. Acaricide application, which is currently the mainstay of tick control, is hampered by high cost, the need for regular application and a selection of multi-acaricide resistant tick populations. In light of this, future tick control approaches are poised to rely on the integration of rational acaricide application and other methods, such as vaccination. To contribute to systematic research-guided efforts to ...[more]

PMID: 31612130

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Project description:Reverse vaccinology is an outstanding strategy to identify antigens with high potential for vaccine development. Different parameters of five prediction programs were used to assess their sensitivity and specificity to identify B-cell epitopes of Chikungunya virus (CHIKV) strains reported in the IEDB database. The results, based on the use of 15 to 20 mer epitopes and the polyproteins to which they belong, were compared to establish the best parameters to optimize the prediction of antigenic peptides of the Mexican strain CHIKV AJV21562.1. LBtope showed the highest specificity when we used the reported epitopes and polyproteins but the worst sensitivity with polyproteins; ABCpred had similar specificity to LBtope only with the epitopes reported and showed moderate specificity when we used polyproteins for the predictions. Because LBtope was more reliable in predicting true epitopes, it was used as a reference program to predict and select six novel epitopes of the Mexican strain of CHIKV according to prediction frequency, viral genome localization, and non-homology with the human proteome. On the other hand, six bioinformatics programs were used with default parameters to predict T-cell epitopes in the CHIKV strains AJV21562.1 and AJV21561.1. The sequences of the polyproteins were analyzed to predict epitopes present in the more frequent HLA alleles of the Mexican population: DQA1*03011, DQA1*0401, DQA1*0501, DQB1*0201, DQB1*0301, DQB1*0302, and DQB1*0402. Fifteen predicted epitopes in the non-structural and 15 predicted epitopes in the structural polyprotein (9- to 16-mers) with the highest scores of each allele were compared to select epitopes with at least 80% identity. Next, the epitopes predicted with at least two programs were aligned to the human proteome, and 12 sequences without identity with the human proteome were identified as potential antigenic candidates. This strategy would be useful to evaluate vaccine candidates against other viral diseases affecting the countries of the Americas and to increase knowledge about these diseases.

Project description:In the wake of the 'omics' explosion of data, reverse vaccinology approaches are being applied more readily as an alternative for the discovery of candidates for next generation diagnostics and vaccines. Promising protective antigens for the control of ticks and tick-borne diseases can be discovered by mining available omics data for immunogenic epitopes. The present study aims to explore the previously obtained Rhipicephalus bursa sialotranscriptome during both feeding and Babesia infection, to select antigenic targets that are either membrane-associated or a secreted protein, as well as unique to the ectoparasite and not present in the mammalian host. Further, they should be capable of stimulating T and B cells for a potential robust immune response, and be non-allergenic or toxic to the host. From the R. bursa transcriptome, 5706 and 3025 proteins were identified as belonging to the surfaceome and secretome, respectively. Following a reverse genetics immunoinformatics pipeline, nine preferred candidates, consisting of one transmembrane-related and eight secreted proteins, were identified. These candidates showed a higher predicted antigenicity than the Bm86 antigen, with no homology to mammalian hosts and exposed regions. Only four were functionally annotated and selected for further in silico analysis, which examined their protein structure, surface accessibility, flexibility, hydrophobicity, and putative linear B and T-cell epitopes. Regions with overlapping coincident epitopes groups (CEGs) were evaluated to select peptides that were further analyzed for their physicochemical characteristics, potential allergenicity, toxicity, solubility, and potential propensity for crystallization. Following these procedures, a set of three peptides from the three R. bursa proteins were selected. In silico results indicate that the designed epitopes could stimulate a protective and long-lasting immune response against those tick proteins, reflecting its potential as anti-tick vaccines. The immunogenicity of these peptides was evaluated in a pilot immunization study followed by tick feeding to evaluate its impact on tick behavior and pathogen transmission. Combining in silico methods with in vivo immunogenicity evaluation enabled the screening of vaccine candidates prior to expensive infestation studies on the definitive ovine host animals.

Dataset Information

Identification of Ixodid Tick-Specific Aquaporin-1 Potential Anti-tick Vaccine Epitopes: An in-silico Analysis.

Publications

Identification of Ixodid Tick-Specific Aquaporin-1 Potential Anti-tick Vaccine Epitopes: An <i>in-silico</i> Analysis.

Similar Datasets

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