ABSTRACT
OBJECTIVE: To analyse the genetic variability of EG95 sequences and provide guidance for EG95 vaccine application against Echinococcus granulosus (E. granulosus). METHODS: We analysed EG95 polymorphism by collecting total 97 different E. granulosus isolates from 12 different host species that originated from 10 different countries. Multiple sequence alignments and the homology were performed by Lasergene 1 (DNASTAR Inc., Madison, WI), and the phylogenetic analysis was performed by using MEGA5.1 (CEMI, Tempe, AZ, USA). In addition, linear and conformational epitopes were analysed, including secondary structure, NXT/S glycosylation, fibronectin type III (FnIII) domain and glycosylphosphatidylinositol anchor signal (GPI-anchor). The secondary structure was predicted by PSIPRED method. RESULTS: Our results indicated that most isolates overall shared 72.6-100% identity in EG95 gene sequence with the published standard EG95 sequence, X90928. However, EG95 gene indeed has polymorphism in different isolates. Phylogenetic analysis showed that different isolates could be divided into three subgroups. Subgroup 1 contained 87 isolates while Subgroup 2 and Subgroup 3 consisted of 3 and 7 isolates, respectively. Four sequences cloned from oncosphere shared a high identity with the parental sequence of the current vaccine, X90928, and they belonged to Subgroup 1. However, in comparison to X90928, several amino acid mutations occurred in most isolates besides oncosphere, which potentially altered the immunodominant linear epitopes, glycosylation sites and secondary structures in EG95 genes. All these variations might change their previous antigenicity and thereby affecting the efficacy of current EG95 vaccine. CONCLUSIONS: This study reveals the genetic variability of EG95 sequences in different E. granulosus isolates, and proposed that more vaccination trials would be needed to test the effectiveness of current EG95 vaccine against distinct isolates in different countries.
ABSTRACT
The aim of the present study was to predict and analyze the secondary structure, and B and T cell epitopes of Echinococcus granulosus antigen 5 (Ag5) using online software in order to investigate its immunogenicity and preliminarily evaluate its potential as an effective antigen peptide vaccine for cystic echinococcosis. The PortParam program was used to analyze molecular weight, the theoretical isoelectric point, instability index and other physicochemical properties. The secondary structure of the Ag5 protein was predicted using Self-Optimized Prediction method With Alignment and the tertiary structure of the Ag5 protein was predicted using 3DLigandSite together with Center for Biological Sequence Analysis Prediction Servers. Furthermore, the Immune Epitope Database software was used to predict B cell epitopes, and T cell epitopes were predicted with the BioInformatics and Molecular Analysis Section and SYFPEITHI programs. The results demonstrated that α-helixes, ß-turns, random coils and extended strands account for 23.35, 10.95, 41.32, and 24.38% of the secondary structure of the Ag5 protein, respectively. Ten potential B cell epitopes of Ag5 were identified as the amino acids sequences 27-39, 70-80, 117-130, 146-168, 250-262, 284-293, 339-349, 359-371, 403-412 and 454-462, and seven potential T cell epitopes were identified as the amino acid sequences 52-60, 57-65, 182-190, 231-239, 273-281, 318-326 and 467-475. Thus, ten B cell epitopes and seven T cell epitopes were identified on Ag5, suggesting the strong immunogenicity of this protein, which could be applied to design antigen peptide vaccines for echinococcosis.
ABSTRACT
AIMS: The aim of this review is to assess the effects of exercise training on the symptoms of depression in heart failure (HF) patients. METHODS AND RESULTS: Randomized controlled trials of exercise training in patients with HF and symptoms of depression were identified. The depression data were pooled using meta-analysis, and 19 studies were identified, with a total of 3447 patients, of which 16 (3226 patients) provided data for the meta-analysis. Exercise training demonstrated significant reductions in the symptoms of depression [standardized mean difference (SMD) -0.38, 95% confidence interval (CI) -0.55 to -0.21], and its antidepressive effect was consistent in a number of HF groups, such as in ages under and over 65 years (SMD -0.14, 95% CI -0.22 to -0.07 vs. SMD -0.44, 95% CI -0.61 to -0.27) and EFs of <50% (SMD -0.38, 95% CI -0.56 to -0.20), as well as in a range of interventional strategies, including the aerobic mode (SMD -0.40, 95% CI -0.61 to -0.19), centre, home, or combined setting (SMD -0.61, 95% CI -0.95 to -0.27 vs. SMD -0.25, 95% CI -0.44 to -0.07 vs. SMD -0.13, 95% CI -0.21 to -0.05), and short or longer training programmes (≤12 weeks, SMD -0.50, 95% CI -0.73 to -0.27; 12-26 weeks, SMD -0.47, 95% CI -0.82 to -0.11; >26 weeks, SMD -0.12, 95% CI -0.20 to -0.04). The beneficial effects were preserved when blind design trials were considered (SMD -0.14, 95% CI -0.22 to -0.07). CONCLUSION: Exercise training significantly decreased the symptoms of depression in patients with HF. This benefit remained unclear in cases of HF with a normal EF and combined aerobic and strength training. Random controlled trials are needed to verify the benefit of exercise in these populations, and in very old, asymptomatic, and severe HF patients.