Evaluation of Echinococcus multilocularis tetraspanins as vaccine candidates against primary alveolar echinococcosis

Dang, Zhisheng; Yagi, Kinpei; Oku, Yuzaburo; Kouguchi, Hirokazu; Kajino, Kiichi; Watanabe, Junichi; Matsumoto, Jun; Nakao, Ryo; Wakaguri, Hiroyuki; Toyoda, Atsushi; Sugimoto, Chihiro

doi:10.1016/j.vaccine.2009.09.045

Cited by 40 publications

(57 citation statements)

References 44 publications

(60 reference statements)

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“…Additionally, transcriptomic analysis of the cestode, Echinococcus granulosus, revealed the existence of other CD63-like tetraspanin family members [44]. Tetraspanins were independently selected as target candidates for vaccination against Echinococcus multilocularis, another tapeworm which causes alveolar echinococcosis, a highly fatal disease dominating parts of Siberia, Central Europe and China [45], [46]. The focus on a tetraspanin-targeting vaccine is also being explored against the human pathogen S. mansoni [47], [48].…”

Section: Protein-mediated Interactionsmentioning

confidence: 99%

Host parasite communications—Messages from helminths for the immune system

Coakley

Buck

Maizels

2016

Molecular and Biochemical Parasitology

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Section: Protein-mediated Interactionsmentioning

confidence: 99%

Host parasite communications—Messages from helminths for the immune system

Coakley

Buck

Maizels

2016

Molecular and Biochemical Parasitology

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“…The regions encoding the LEL (large extracellular loop) domain of Em-TSP1 and Em-TSP3 were amplified from the full-length enriched cDNA library of E. multilocularis metacestode, subcloned into the pBAD/Thio-TOPO vector (Invitrogen, USA), expressed and purified as previously described [18]. Briefly, E. coli TOP10 cells (Invitrogen, USA) were transformed with a recombinant plasmid according to the manufacturer's instructions (pBAD/TOPO® ThioFusion™ Expression Kit, Invitrogen, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Samples were vigorously vortexed and centrifuged to collect the supernatants. Indirect ELISA was performed for the antibody analysis as previously described [18]. Briefly, 96-well microtiter plates (Corning, USA) were coated with rEm-TSP1/rEm-TSP3 proteins (0.25 µg/well), blocked with 5% skim milk.…”

Section: Methodsmentioning

confidence: 99%

“…Much progress has been made in vaccine development against Schistosoma parasite infection using a surface protein, tetraspanin [15]–[17]. In our previous study, seven tetraspanins have been identified in E. multilocularis larvae and are used to develop vaccines against E. multilocularis infection, which induced significant levels of protection when subcutaneously administered with Freund's adjuvant [18]. Remarkably, vaccinations with rEm-TSP1 and -TSP3 were shown to induce strong serum IgG immune responses in immunized BALB/c mice and received an >85% of liver cyst lesion number reductions (CLNR) after orally challenged with parasite eggs.…”

Section: Introductionmentioning

confidence: 99%

“…In experiment I, we compared the i.n. vaccine efficacy between rEm-TSP1 and -TSP3 which showed >85% of liver CLNR in our previous study, when used as an s.c. vaccine [18]. In experiment II, we evaluated the vaccine efficacy of rEm-TSP3 plus Freund's adjuvant (s.c.) versus rEm-TSP3 plus CpG adjuvant (i.n.)…”

Section: Introductionmentioning

confidence: 99%

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A Pilot Study on Developing Mucosal Vaccine against Alveolar Echinococcosis (AE) Using Recombinant Tetraspanin 3: Vaccine Efficacy and Immunology

et al. 2012

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Background We have previously evaluated the vaccine efficacies of seven tetraspanins of Echinococcus multilocularis (Em-TSP1–7) against alveolar echinococcosis (AE) by subcutaneous (s.c.) administration with Freund's adjuvant. Over 85% of liver cyst lesion number reductions (CLNR) were achieved by recombinant Em-TSP1 (rEm-TSP1) and -TSP3 (rEm-TSP3). However, to develop an efficient and safe human vaccine, the efficacy of TSP mucosal vaccines must be thoroughly evaluated. Methodology/Principal Findings rEm-TSP1 and -TSP3 along with nontoxic CpG ODN (CpG oligodeoxynucleotides) adjuvant were intranasally (i.n.) immunized to BALB/c mice and their vaccine efficacies were evaluated by counting liver CLNR (experiment I). 37.1% ( p <0.05) and 62.1% ( p <0.001) of CLNR were achieved by these two proteins, respectively. To study the protection-associated immune responses induced by rEm-TSP3 via different immunization routes (i.n. administration with CpG or s.c. immunization with Freund's adjuvant), the systemic and mucosal antibody responses were detected by ELISA (experiment II). S.c. and i.n. administration of rEm-TSP3 achieved 81.9% ( p <0.001) and 62.8% ( p <0.01) CLNR in the liver, respectively. Both the immunization routes evoked strong serum IgG, IgG1 and IgG2α responses; i.n. immunization induced significantly higher IgA responses in nasal cavity and intestine compared with s.c. immunization ( p <0.001). Both immunization routes induced extremely strong liver IgA antibody responses ( p <0.001). The Th1 and Th2 cell responses were assessed by examining the IgG1/IgG2α ratio at two and three weeks post-immunization. S.c. immunization resulted in a reduction in the IgG1/IgG2α ratio (Th1 tendency), whereas i.n. immunization caused a shift from Th1 to Th2. Moreover, immunohistochemistry showed that Em-TSP1 and -TSP3 were extensively located on the surface of E. multilocularis cysts, protoscoleces and adult worms with additional expression of Em-TSP3 in the inner part of protoscoleces and oncospheres. Conclusions Our study indicated that i.n. administration of rEm-TSP3 with CpG is able to induce both systemic and local immune responses and thus provides significant protection against AE.

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Proteomic analysis of the Echinococcus granulosus metacestode during infection of its intermediate host

et al. 2010

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Cystic hydatid disease (CHD) is caused by infection with the Echinococcus granulosus metacestode and affects both humans and livestock. In this work, we performed a proteomic analysis of the E. granulosus metacestode during infection of its intermediate bovine host. Parasite proteins were identified in different metacestode components (94 from protoscolex, 25 from germinal layer and 20 from hydatid cyst fluid), along with host proteins (58) that permeate into the hydatid cyst, providing new insights into host-parasite interplay. E. granulosus and platyhelminth EST data allowed successful identification of proteins potentially involved in downregulation of host defenses, highlighting possible evasion mechanisms adopted by the parasite to establish infection. Several intracellular proteins were found in hydatid cyst fluid, revealing a set of newly identified proteins that were previously thought to be inaccessible for inducing or modulating the host immune response. Host proteins identified in association with the hydatid cyst suggest that the parasite may bind/adsorb host molecules with nutritional and/or immune evasion purposes, masking surface antigens or inhibiting important effector molecules of host immunity, such as complement components and calgranulin. Overall, our results provide valuable information on parasite survival strategies in the adverse host environment and on the molecular mechanisms underpinning CHD immunopathology.

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Evaluation of Echinococcus multilocularis tetraspanins as vaccine candidates against primary alveolar echinococcosis

Abstract: Vaccination conferred protective rates to mice ranging from 0% (TSP5, 6, 7) to maximally 33% (TSP1, 3). The results indicated that recombinant tetraspanins have varying protective effects against primary alveolar echinococcosis and could be used in vaccine development.

Cited by 40 publications

References 44 publications

Host parasite communications—Messages from helminths for the immune system

Host parasite communications—Messages from helminths for the immune system

A Pilot Study on Developing Mucosal Vaccine against Alveolar Echinococcosis (AE) Using Recombinant Tetraspanin 3: Vaccine Efficacy and Immunology

Proteomic analysis of the Echinococcus granulosus metacestode during infection of its intermediate host

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