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A novel B- and helper T-cell epitopes-based prophylactic vaccine against Echinococcus granulosus.

ABSTRACT: Introduction: In this study, we targeted the worm stage of Echinococcus granulosus to design a novel multi-epitope B- and helper T-cell based vaccine construct for immunization of dogs against this multi-host parasite. Methods: The vaccine was designed based on the local Eg14-3-3 antigen (Ag). DNA samples were extracted from the protoscoleces of the infected sheep's liver, and then subjected to the polymerase chain reaction (PCR) with 14-3-3 specific forward and reverse primers. For the vaccine designing, several in silico steps were undertaken. Three-dimensional (3D) structure of the local Eg14-3-3 Ag was modeled by EasyModeller software. The protein modeling accuracy was then analyzed via various validation assays. Potential transmembrane helix, signal peptide, post-translational modifications and allergenicity of Eg14-3-3 were evaluated as the preliminary measures of B-cell epitopes (BEs ) prediction. Having used many web-servers, a well-designed process was carried out for improved prediction of BEs. High ranked linear and conformational BEs were utilized for engineering the final vaccine construct. Possible T-helper epitopes (TEs) were identified by the molecular docking between 13-mer fragments of the Eg14-3-3 Ag and two high frequent dog class II MHC alleles (i.e., DLA-DRB1*01101 and DRB1*01501). The epitopes coverage was evaluated by Shannon's variability plot. Results: The final designed construct was analyzed based on different physicochemical properties, which was then codon optimized for high-level expression in Escherichia coli k12. This minigene construct is the first dog-specific epitopic vaccine construct that is established based on TEs with high-binding affinity to canine MHC alleles. Conclusion: This in silico study is the first part of a multi-antigenic vaccine designing work that represents as a novel dog-specific vaccine against E. granulosus. Here, we present key data on the step-by-step methodologies used for designing this de novo vaccine, which is under comprehensive in vivo investigations.

SUBMITTER: Pourseif MM

PROVIDER: S-EPMC5915707 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A novel B- and helper T-cell epitopes-based prophylactic vaccine against Echinococcus granulosus.

Pourseif Mohammad M MM Moghaddam Gholamali G Daghighkia Hossein H Nematollahi Ahmad A Omidi Yadollah Y

BioImpacts : BI 20171220 1

Introduction: In this study, we targeted the worm stage of Echinococcus granulosus to design a novel multi-epitope B- and helper T-cell based vaccine construct for immunization of dogs against this multi-host parasite. Methods: The vaccine was designed based on the local Eg14-3-3 antigen (Ag). DNA samples were extracted from the protoscoleces of the infected sheep's liver, and then subjected to the polymerase chain reaction (PCR) with 14-3-3 specific forward an ...[more]

PMID: 29713601

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Project description:BackgroundCystic echinococcosis (CE) is caused by the infection of Echinococcus granulosus sensu lato (E. granulosus s.l.), one of the most harmful zoonotic helminths worldwide. Infected dogs are the major source of CE transmission. While praziquantel-based deworming is a main measure employed to control dog infections, its efficacy is at times compromised by the persistent high rate of dog re-infection and the copious discharge of E. granulosus eggs into the environment. Therefore, the dog vaccine is a welcome development, as it offers a substantial reduction in the biomass of E. granulosus. This study aimed to use previous insights into E. granulosus functional genes to further assess the protective efficacy of six recombinant proteins in dogs using a two-time injection vaccination strategy.MethodsWe expressed and combined recombinant E. granulosus triosephosphate isomerase (rEgTIM) with annexin B3 (rEgANXB3), adenylate kinase 1 (rEgADK1) with Echinococcus protoscolex calcium binding protein 1 (rEgEPC1), and fatty acid-binding protein (rEgFABP) with paramyosin (rEgA31). Beagle dogs received two subcutaneous vaccinations mixed with Quil-A adjuvant, and subsequently orally challenged with protoscoleces two weeks after booster vaccination. All dogs were sacrificed for counting and measuring E. granulosus tapeworms at 28 days post-infection, and the level of serum IgG was detected by ELISA.ResultsDogs vaccinated with rEgTIM&rEgANXB3, rEgADK1&rEgEPC1, and rEgFABP-EgA31 protein groups exhibited significant protectiveness, with a worm reduction rate of 71%, 57%, and 67%, respectively, compared to the control group (P < 0.05). Additionally, the vaccinated groups exhibited an inhibition of worm growth, as evidenced by a reduction in body length and width (P < 0.05). Furthermore, the level of IgG in the vaccinated dogs was significantly higher than that of the control dogs (P < 0.05).ConclusionThese verified candidates may be promising vaccines for the prevention of E. granulosus infection in dogs following two injections. The rEgTIM&rEgANXB3 co-administrated vaccine underscored the potential for the highest protective efficacy and superior protection stability for controlling E. granulosus infections in dogs.

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A novel B- and helper T-cell epitopes-based prophylactic vaccine against Echinococcus granulosus.

Publications

A novel B- and helper T-cell epitopes-based prophylactic vaccine against <i>Echinococcus granulosus</i>.

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