Bioinformatic prediction and identification of immunogenic epitopes of the antigenic 14-3-3 protein of Echinococcus multilocularis

Wei, Wei; Wang, Lei; Zhou, Pei; Jiang, Bai-Li; Liu, Haisheng; Feng, Lin; Ge, Ri‐Li; Tang, Feng; Li, Runle

doi:10.1016/j.actatropica.2021.105955

Cited by 7 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Liver function is not a particularly sensitive evaluation index in clinical cases and it is only used to determine the preoperative nutritional status of patients with hepatic alveolar echinococcosis and AE-related autologous liver transplantation in order to evaluate the effect of surgery (24, 25). The expression of key proteins of E. multilocularis is not measured in animal model (7,16,21), because few substances are secreted into the tissue due to the presence of insect protein and cyst and no specific antibody is currently available for verification. For these reasons, we have evaluated not only the sizes of cysts but also parasite infiltration and growth in the liver through MRI, ultrasound and pathological examination.…”

Section: Discussionmentioning

confidence: 99%

“…Surgery and anti-helminthic drugs are the treatment of choice for AE (3). Some proteins of E. multilocularis with high immunogenicity could induce immune responses to prevent infection (4)(5)(6)(7). Our previous study has shown that vaccination with dominant epitopes, such as EMY162, Glut1, TSP3, 14-3-3 and EM-LAP, could significantly decrease the number and size of cysts in a mouse model infected with E. Multilocularis metacestodes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic effect on Alveolar echinococcosis by targeting EM-Leucine aminopeptidase

Zhou

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Alveolar echinococcosis (AE) is a parasitic disease caused by E. multilocularis metacestodes and it is highly prevalent in the northern hemisphere. We have previously found that vaccination with E. multilocularis Leucine aminopeptidase (EM-LAP) induced specific immune response and had an inhibiting effect on the parasites. In this study, the therapeutic effect of recombinant EM-LAP (rEM-LAP) on AE was evaluated and verified using Ubenimex, a broad-spectrum inhibitor of LAP. The results reveal that rEM-LAP could inhibit cyst growth and invasion and induce specific immunity response in BALB/c mice infected with E. multilocularis protoscoleces. The ultrasonic, MRI, and morphological results show that treatment with rEM-LAP inhibits E. multilocularis infection and reduces cyst weight, number, fibrosis and invasion. The same effect is observed for the treatment with Ubenimex by inhibiting LAP activity. The indirect ELISA shows that rEM-LAP could induce specific immunity response and produce high levels of IgG, IgG1, IgG2a, IgM, and IgA, and the serum levels of IFN-γ and IL-4 are significantly increased compared to the control groups, indicating that treatment with rEM-LAP leads to a Th1 and Th2 mixed-type immune response. This study suggests that EM-LAP could be a potential therapeutic target of E. multilocularis infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Therapeutic effect on Alveolar echinococcosis by targeting EM-Leucine aminopeptidase

Zhou

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…GILE was purified by high-affinity Ni-NTA Resin. After concentration in polyethylene glycol 20000 (PEG20000), the purified target proteins were subjected to 12% SDS-PAGE and Western blot analysis ( 12 ) and stored at −80°C.…”

Section: Methodsmentioning

confidence: 99%

“…Our animal experiments have demonstrated that EM14-3-3 has two dominant antigen epitopes of B cells, two Th1 dominant antigen epitopes, and one Th2 dominant antigen epitope. This work provides a basis for the development of effective and safe vaccines targeting the epitopes of E. multilocularis ( 12 , 13 ).However, the use of a single epitope vaccine might not be adequate to prevent E. multilocularis infection because different types and amounts of proteins would be expressed at different developmental stages of E. multilocularis ( 14 ). In this study, a multi-epitope vaccine GILE was designed using bioinformatics and molecular biology techniques based on the dominant epitopes of E. multilocularis EMY162, LAP and GLUT1 (EmEMY162, EmLAP, and EmGLUT1) identified in our previous studies ( 9 , 10 , 15 ), and its immune protective effect against E. multilocularis infection was evaluated in mice.…”

Section: Introductionmentioning

confidence: 99%

A multi-epitope vaccine GILE against Echinococcus Multilocularis infection in mice

Zhou

Zhou²,

Huayu³

et al. 2023

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

IntroductionThe objective of this study is to construct a multi-epitope vaccine GILE containing B-cell and T-cell epitopes against Echinococcus Multilocularis (E. multilocularis) infection based on the dominant epitopes of E. multilocularis EMY162, LAP, and GLUT1.MethodsThe structure and hydrophobicity of GILE were predicted by SWISSMODEL, pyMOL, SOPMA and VMD, and its sequence was optimized by Optimum™ Codon. The GILE gene was inserted into pCzn1 and transformed into Escherichia coli Arctic express competent cells. IPTG was added to induce the expression of recombinant proteins. High-purity GILE recombinant protein was obtained by Ni-NTA Resin. BALB/c mice were immunized with GILE mixed with Freund’s adjuvant, and the antibody levels and dynamic changes in the serum were detected by ELISA. Lymphocyte proliferation was detected by MTS. The levels of IFN-g and IL-4 were detected by ELISpot and flow cytometry (FCM). T cells were detected by FCM. The growth of hepatic cysts was evaluated by Ultrasound and their weights were measured to evaluate the immune protective effect of GILE.ResultsThe SWISS-MODEL analysis showed that the optimal model was EMY162 95-104―LAP464-479―LAP495-510―LAP396-410―LAP504-518―EMY162112-126. The SOPMA results showed that there were Alpha helix (14.88%), Extended strand (26.25%), Beta turn (3.73%) and Random coil (45.82%) in the secondary structure of GILE. The restriction enzyme digestion and sequencing results suggested that the plasmid pCzn1-GILE was successfully constructed. The SDSPAGE results indicated that the recombinant protein was 44.68 KD. The ELISA results indicated that mice immunized with GILE showed higher levels of serum antibodies compared to the PBS group. The FCM and ELISpot results indicated that mice immunized with GILE secreted more IFN-g and IL-4. Immunization with GILE also led to a significant decrease in the maximum diameter and weight of cysts and stimulated the production of CD4+ and CD8+ T Cell.DiscussionA multi-epitope vaccine GILE with good immunogenicity and antigenicity has been successfully constructed in this study, which may provide important theoretical and experimental bases for the prevention and treatment of E. multilocularis infection.

show abstract

“…[10] 14-3-3 is present in the germinal layer and extracellular vesicles of E. multilocularis, possibly linked to the invasive growth of E. multilocularis. [11] EMY162, a host-protective…”

mentioning

confidence: 99%

A Bioengineered Nanovesicle Vaccine Boosts T‐B cell Interaction for Immunotherapy of Echinococcus multilocularis

An,

Xiang,

Liu

et al. 2024

Angewandte Chemie

Self Cite

View full text Add to dashboard Cite

Alveolar echinococcosis (AE) is a zoonotic parasitic disease, resulting from being infected with the metacestode larvae of the tapeworm Echinococcus multilocularis. Novel prophylactic and therapeutic interventions are urgently needed since the current chemotherapy displays limited efficiency in AE treatment. Bioengineered nano cellular membrane vesicles are widely used for displaying the native conformational epitopes because of their unique structure and biocompatibility. In this study, four T‐cells and four B‐cells dominant epitope peptides of E. multilocularis with high immunogenicity were engineered into the Vero cell surface to construct a membrane vesicle nanovaccine for the treatment of AE. The results showed that the nanovesicle vaccine can efficiently activate dendritic cells, induce specific T/B cells to form a mutually activated circuit, and inhibit E. multilocularis infection. This study presents for the first time a nanovaccine strategy that can completely eliminate the burden of E. multilocularis.

show abstract

Bioinformatic prediction and identification of immunogenic epitopes of the antigenic 14-3-3 protein of Echinococcus multilocularis

Cited by 7 publications

References 33 publications

Therapeutic effect on Alveolar echinococcosis by targeting EM-Leucine aminopeptidase

Therapeutic effect on Alveolar echinococcosis by targeting EM-Leucine aminopeptidase

A multi-epitope vaccine GILE against Echinococcus Multilocularis infection in mice

A Bioengineered Nanovesicle Vaccine Boosts T‐B cell Interaction for Immunotherapy of Echinococcus multilocularis

Contact Info

Product

Resources

About