44 research outputs found
Bioinformatics analysis of calcium-dependent protein kinase 4 (CDPK4) as Toxoplasma gondii vaccine target
Objectives Toxoplasma gondii (T. gondii), an obligate intracellular apicomplexan parasite, could affect numerous warm-blooded animals, such as humans. Calcium-dependent protein kinases (CDPKs) are essential Ca2+ signaling mediators and participate in parasite host cell egress, outer membrane motility, invasion, and cell division. Results Several bioinformatics online servers were employed to analyze and predict the important properties of CDPK4 protein. The findings revealed that CDPK4 peptide has 1158 amino acid residues with average molecular weight (MW) of 126.331 KDa. The aliphatic index and GRAVY for this protein were estimated at 66.82 and - 0.650, respectively. The findings revealed that the CDPK4 protein comprised 30.14 and 34.97 alpha-helix, 59.84 and 53.54 random coils, and 10.02 and 11.49 extended strand with SOPMA and GOR4 tools, respectively. Ramachandran plot output showed 87.87, 8.40, and 3.73 of amino acid residues in the favored, allowed, and outlier regions, respectively. Also, several potential B and T-cell epitopes were predicted for CDPK4 protein through different bioinformatics tools. Also, antigenicity and allergenicity evaluation demonstrated that this protein has immunogenic and non-allergenic nature. This paper presents a basis for further studies, thereby provides a fundamental basis for the development of an effective vaccine against T. gondii infection
Environmental risk factors for Toxoplasma gondii infections and the impact of latent infections on allostatic load in residents of Central North Carolina
Abstract
Background
Toxoplasma gondii infection can be acquired through ingestion of infectious tissue cysts in undercooked meat or environmental oocysts excreted by cats. This cross-sectional study assessed environmental risk factors for T. gondii infections and an association between latent infections and a measure of physiologic dysregulation known as allostatic load.
Methods
Serum samples from 206 adults in the Durham-Chapel Hill, North Carolina area were tested for immunoglobulin (IgG) responses to T. gondii using commercial ELISA kits. Allostatic load was estimated as a sum of 15 serum biomarkers of metabolic, neuroendocrine and immune functions dichotomized at distribution-based cutoffs. Vegetated land cover within 500 m of residences was estimated using 1 m resolution data from US EPA’s EnviroAtlas.
Results
Handling soil with bare hands at least weekly and currently owning a cat were associated with 5.3 (95% confidence limits 1.4; 20.7) and 10.0 (2.0; 50.6) adjusted odds ratios (aOR) of T. gondii seropositivity, respectively. There was also a significant positive interaction effect of handling soil and owning cats on seropositivity. An interquartile range increase in weighted mean vegetated land cover within 500 m of residence was associated with 3.7 (1.5; 9.1) aOR of T. gondii seropositivity. Greater age and consumption of undercooked pork were other significant predictors of seropositivity. In turn, T. gondii seropositivity was associated with 61% (13%; 130%) greater adjusted mean allostatic load compared to seronegative individuals. In contrast, greater vegetated land cover around residence was associated with significantly reduced allostatic load in both seronegative (p < 0.0001) and seropositive (p = 0.004) individuals.
Conclusions
Residents of greener areas may be at a higher risk of acquiring T. gondii infections through inadvertent ingestion of soil contaminated with cat feces. T. gondii infections may partially offset health benefits of exposure to the natural living environment
In silico analysis and prediction of immunogenic epitopes for pre-erythrocytic proteins of the deadly Plasmodium falciparum
Malaria is the deadliest parasitic disease in tropical and subtropical areas around the world, with considerable morbidity and mortality, particularly due to the life-threatening Plasmodium falciparum. The present in silico investigation was performed to reveal the biophysical characteristics and immunogenic epitopes of the six pre-erythrocytic proteins of the P. falciparum using comprehensive immunoinformatics approaches. For this aim, different web servers were employed to predict subcellular localization, antigenicity, allergenicity, solubility, physico-chemical properties, post-translational modification sites (PTMs), the presence of signal peptide and transmembrane domains. Moreover, the secondary and tertiary structures of the proteins were revealed followed by refinement and validations. Finally, NetCTL server was used to predict cytotoxic T-lymphocyte (CTL) epitopes, followed by subsequent screening in terms of antigenicity and immunogenicity. Also, IEDB server was utilized to predict helper T-lymphocyte (HTL) epitopes, followed by screening regarding interferon gamma induction and population coverage. These proteins showed appropriate antigenicity, abundant PTMs as well as many CTL and HTL epitopes, which could be directed for future vaccination studies in the context of multi-epitope vaccine design
Multi-epitope vaccine against cystic echinococcosis using immunodominant epitopes from EgA31 and EgG1Y162 antigens
Cystic echinococcosis (CE) is a near-cosmopolitan public health concern, especially in developing countries. Parasite ova shed via definitive host feces are responsible for livestock and occasionally human infection, leading to hydatid cysts. Immunization using proper antigens is a good immunoprophylactic strategy. This study was aimed to design a multi-epitope vaccine using EgA31 and EgG1Y162 antigens. Top high-ranked B-cell epitopes and major histocompatibility complex (MHC)-binding epitopes were predicted and selected to construct the vaccine model. Then, physico-chemical features, secondary and tertiary structures, refinement and validations were all evaluated using web servers for the multi-epitope vaccine construct. Finally, non-linear B-cell epitopes were determined for vaccine-antibody interactions. Moreover, the vaccine construct was subjected to disulfide engineering, molecular docking with human MHC-I and MHC-II molecules as well as codon adaptation and in silico cloning processes. In conclusion, this multimeric CE vaccine needs experimental and clinical confirmations to be considered as an actually immunogenic vaccine model. © 202
Shedding light on biochemical features and potential immunogenic epitopes of Neospora caninum SAG1: In silico study
Vaccination is the only feasible way for appropriate prevention of Neospora caninum infection. The present in silico study was done to evaluate the physico-chemical properties and determine immunogenic epitopes of N. caninum SAG1 protein as a possible vaccine candidate. Web-based tools were used to predict physico-chemical properties, antigenicity, allergenicity, solubility, post-translational modification (PTM) sites, transmembrane domains and signal peptide, secondary and tertiary structures as well as intrinsically disordered regions, followed by identification and screening of potential linear and conformational B-cell epitopes and those peptides having affinity to bind mouse major histocompatibility complex (MHC) and cytotoxic T lymphocyte (CTL). The protein was stable in a test tube, had 319 residues with a molecular weight of 33.07 kDa, representing aliphatic index of 76.68 (thermotolerant) and GRAVY score of 0.031 (hydrophobic). There were 42 PTM sites and an N-terminally-located signal peptide in the sequence. Secondary structure comprised mostly by random coils, followed by strands and helices. Ramachandran plot of the refined model showed 71.7, 24.9, 3.0 and 0.4 residues in the favored, additional allowed, generously allowed and disallowed regions, correspondingly. Additionally, various potential B-cell (linear and conformational), CTL and MHC-binding epitopes were predicted for N. caninum SAG1. The findings of the present in silico study are a premise for vaccination strategies against neosporosis. © 202
Engineering a multi-epitope vaccine candidate against Leishmania infantum using comprehensive Immunoinformatics methods
Visceral leishmaniasis (VL) is a severe disease with particular endemicity in over 80 countries worldwide. There is no approved human vaccine against VL in the market. This study was aimed at designing and evaluation of a multimeric vaccine candidate against Leishmania infantum through utilization of helper T lymphocyte (HTL) and cytotoxic T lymphocyte (CTL) immunodominant proteins from histone H1, KMP11, LACK and LeIF antigens. Top-ranked mouse MHC-I, MHC-II binders and CTL epitopes were predicted and joined together via spacers. Also, a TLR-4 agonist (RS-09 synthetic protein) and His-tag were added to the N- and C-terminal of the vaccine sequence, respectively. The final chimeric vaccine had a length of 184 amino acids with a molecular weight of 18.99 kDa. Physico-chemical features showed a soluble, highly-antigenic and non-allergenic candidate. Secondary and tertiary structures were predicted, and subsequent analyses confirmed the construct stability that was capable to properly interact with TLR-4/MD2 receptor. Immunoinformatics simulation displayed potent stimulation of T cell immune responses, with particular rise in IFN-gamma, upon vaccination with the proposed multi-epitope candidate. In conclusion, immunoinformatics data demonstrated a highly antigenic vaccine candidate in mouse, which could develop considerable levels clearance mechanisms and other components of cellular immune profile, and can be directed for VL prophylactic purposes
Construction of a multi-epitope protein for human Toxocara canis detection: Immunoinformatics approach multi-epitope construct for T. canis serodiagnosis
Toxocariasis is a global public health concern, particularly in children. Serological diagnosis of the infection is routinely applied to detect specific anti-Toxocara antibodies. Current in silico study was contrived to design a multi-epitope protein using a wide array of immunoinformatics web servers for improved serodiagnosis. Top, high-ranked B-cell epitopes as well as IL-4 and IL-10 inducing epitopes were predicted, screened and selected to construct the chimeric protein. Then, prediction of antigenicity, solubility and physico-chemical features, secondary and tertiary structures, 3D model refinement and validations was done using various web servers. Finally, conformational B-cell epitopes were determined for possible protein-antibody interactions. Moreover, the final construct was subjected to disulfide engineering, codon adaptation, in silico cloning as well as molecular docking with human TLR-2 molecule. In conclusion, this multi-epitope construct needs to be evaluated experimentally, in order to be used in commercial serodiagnostic kits. © 202
Engineering a multi-epitope vaccine candidate against Leishmania infantum using comprehensive Immunoinformatics methods
Visceral leishmaniasis (VL) is a severe disease with particular endemicity in over 80 countries worldwide. There is no approved human vaccine against VL in the market. This study was aimed at designing and evaluation of a multimeric vaccine candidate against Leishmania infantum through utilization of helper T lymphocyte (HTL) and cytotoxic T lymphocyte (CTL) immunodominant proteins from histone H1, KMP11, LACK and LeIF antigens. Top-ranked mouse MHC-I, MHC-II binders and CTL epitopes were predicted and joined together via spacers. Also, a TLR-4 agonist (RS-09 synthetic protein) and His-tag were added to the N- and C-terminal of the vaccine sequence, respectively. The final chimeric vaccine had a length of 184 amino acids with a molecular weight of 18.99 kDa. Physico-chemical features showed a soluble, highly-antigenic and non-allergenic candidate. Secondary and tertiary structures were predicted, and subsequent analyses confirmed the construct stability that was capable to properly interact with TLR-4/MD2 receptor. Immunoinformatics simulation displayed potent stimulation of T cell immune responses, with particular rise in IFN-gamma, upon vaccination with the proposed multi-epitope candidate. In conclusion, immunoinformatics data demonstrated a highly antigenic vaccine candidate in mouse, which could develop considerable levels clearance mechanisms and other components of cellular immune profile, and can be directed for VL prophylactic purposes
Current situation and future prospects ofEchinococcus granulosusvaccine candidates: A systematic review
Cystic echinococcosis is a worldwide zoonotic disease, represents a threat for livestock and humans, manifests as a quiescent, subclinical and chronic hydatid cyst infection. The disease imposes high expenditures and economic losses in medical and veterinary. Prophylactic vaccination would be one of the effective preventive health care against echinococcosis. During the last decades, many studies have characterized the protective antigens ofEchinococcus granulosusand their role in immunization of various animal host species. Herein, we aimed to systematically evaluate and represent the best antigens as possible vaccine candidates for cystic echinococcosis. Data were systematically searched from five databases including ProQuest, PubMed, Scopus, ScienceDirect and Web of Science, up to 1 February 2020. Two reviewers independently screened and assessed data extraction and quality assessment. A total of 47 articles were eligible for inclusion criteria in the current study. The most common antigens used for vaccination againstE. granulosuswere EG95 and antigen B. Freund's adjuvant and Quil A have been predominantly utilized. In addition, regarding the antigen delivery, animal models, measurement of immune responses and reduction in hydatid cyst have been discussed in the text. The data demonstrated that DNA vaccines with antigen B and recombinant protein vaccines based on EG95 antigen have the best results and elicited protective immune responses
Neospora caninum SRS2 Protein: Essential Vaccination Targets and Biochemical Features for Next-Generation Vaccine Design
Vaccination is a standout preventive measure to combat neosporosis among cattle herds. The present in silico study was done to evaluate the physicochemical properties and potent immunogenic epitopes of N. caninum SRS2 protein as a possible vaccine candidate. Web-based tools were used to predict physicochemical properties, antigenicity, allergenicity, solubility, posttranslational modification (PTM) sites, transmembrane domains and signal peptide, and secondary and tertiary structures as well as intrinsically disordered regions, followed by identification and screening of potential linear and conformational B-cell epitopes and those peptides having affinity to bind mouse major histocompatibility complex (MHC) and cytotoxic T lymphocyte (CTL). The protein had 401 residues with a molecular weight of 42 kDa, representing aliphatic index of 69.35 (thermotolerant) and GRAVY score of -0.294 (hydrophilic). There were 53 PTM sites without a signal peptide in the sequence. Secondary structure comprised mostly by extended strand, followed by helices and coils. The Ramachandran plot of the refined model showed 90.2, 8.8, 0.5, and 0.5 residues in the favored, additional allowed, generously allowed, and disallowed regions, correspondingly. Additionally, various potential B-cell (linear and conformational), CTL, and MHC-binding epitopes were predicted for N. caninum SRS2. These epitopes could be further utilized in the multiepitope vaccine constructs directed against neosporosis