Characterization of a novel vaccine candidate and serine proteinase inhibitor from Schistosoma japonicum (Sj serpin)

Yan, Yutao; Liu, Shuxian; GuangCheng, Song; Xu, Yun; Dissous, Colette

doi:10.1016/j.vetpar.2005.04.038

Cited by 37 publications

(35 citation statements)

References 7 publications

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“…Serine proteinase inhibitors (serpins) represent an important superfamily of endogenous inhibitors that regulate proteolytic events active in a variety of physiological functions. Yan et al (169) used immunological screening of an S. japonicum adult worm cDNA expression library with sera of Microtus fortis, a naturally resistant rodent host, and identified one clone that encoded a sequence homologous to those of the serpin superfamily. The full-length sequence encoding S. japonicum serpin was amplified from adult worm cDNA by using 5Ј rapid amplification of cDNA ends-PCR (5Ј RACE-PCR) and subsequently cloned into the prokaryotic expression vector pET28c.…”

Section: Paramyosin (Sj97)mentioning

confidence: 99%

Current Status of Vaccines for Schistosomiasis

2008

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SUMMARY Schistosomiasis, caused by trematode blood flukes of the genus Schistosoma, is recognized as the most important human helminth infection in terms of morbidity and mortality. Infection follows direct contact with freshwater harboring free-swimming larval (cercaria) forms of the parasite. Despite the existence of the highly effective antischistosome drug praziquantel (PZQ), schistosomiasis is spreading into new areas, and although it is the cornerstone of current control programs, PZQ chemotherapy does have limitations. In particular, mass treatment does not prevent reinfection. Furthermore, there is increasing concern about the development of parasite resistance to PZQ. Consequently, vaccine strategies represent an essential component for the future control of schistosomiasis as an adjunct to chemotherapy. An improved understanding of the immune response to schistosome infection, both in animal models and in humans, suggests that development of a vaccine may be possible. This review considers aspects of antischistosome protective immunity that are important in the context of vaccine development. The current status in the development of vaccines against the African (Schistosoma mansoni and S. haematobium) and Asian (S. japonicum) schistosomes is then discussed, as are new approaches that may improve the efficacy of available vaccines and aid in the identification of new targets for immune attack.

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Section: Paramyosin (Sj97)mentioning

confidence: 99%

Current Status of Vaccines for Schistosomiasis

2008

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“…This organism possesses three serpin genes and again one of these encodes a protein very similar (approximately 65% identical) to ShSPI. Akin to ShSPI, the S. japonicum protein (Sj serpin; UniProt entry Q967L9; GeneDB name Sjp_0085750) was originally identified in a search for potential vaccination targets and immunofluorescence revealed that it also localizes to the tegument of the parasite (Yan et al, 2005).…”

Section: Biological Role Of Shspimentioning

confidence: 99%

“…Within this environment, the protein was hypothesized to function as an inhibitor of coagulation of ingested blood (Hall et al, 2011). Indeed, immunofluorescence studies of Sj serpin using sliced S. japonicum samples revealed distinct staining of intestinal epithelia in addition to the tegument (Yan et al, 2005) and, retrospectively, our previous studies on ShSPI using intact parasites are compatible with a similar distribution in S. haematobium (Blanton et al, 1994). In light of these results, we cannot exclude that in addition to being elastase inhibitors, ShSPI and its orthologues might target additional host proteases.…”

Section: Biological Role Of Shspimentioning

confidence: 99%

Three-dimensional structure of a schistosome serpin revealing an unusual configuration of the helical subdomain

Granzin¹,

Huang²,

Topbaş³

et al. 2012

Acta Crystallogr D Biol Cryst

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Parasitic organisms are constantly challenged by the defence mechanisms of their respective hosts, which often depend on serine protease activities. Consequently, protease inhibitors such as those belonging to the serpin superfamily have emerged as protective elements that support the survival of the parasites. This report describes the crystal structure of ShSPI, a serpin from the trematode Schistosoma haematobium. The protein is exposed on the surface of invading cercaria as well as of adult worms, suggesting its involvement in the parasite–host interaction. While generally conforming to the well established serpin fold, the structure reveals several distinctive features, mostly concerning the helical subdomain of the protein. It is proposed that these peculiarities are related to the unique biological properties of a small serpin subfamily which is conserved among pathogenic schistosomes.

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“…20 Schistosoma japonicum (S. japonicum) serpin is located on the tegument in S. japonicum adult worms and is speculated to be a vaccine candidate or a novel target for anti-schistosome drugs. 19 Parasitederived serpins with signal peptide are suggested to play essential roles in the survival of the parasites in the hosts via host immune evasion and protection from exogenous host proteases. 13 The expression of the CsSERPIN and CsSERPIN3 at metacercariae stage was significantly high than that at adult stage (see supplementary material online for this article www.maneyonline.com/doi/suppl/10.1179/ 2047773214Y.0000000138), which gives us a clue that the two CsSERPINs play an important role in metacercariae.…”

Section: Discussionmentioning

confidence: 99%

Comparison of two serpins ofClonorchis sinensisby bioinformatics, expression, and localization in metacercaria

Yang

Wang

et al. 2014

Pathogens and Global Health

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Clonorchiasis, which has been an important public health problem in China, is caused by ingestion of raw or undercooked fish contaminated by live metacercaria. Therefore, preventing fish from infecting is of great significance for controlling the disease. SERPINs (serine protease inhibitors) are well known as negative regulators of hemostasis, thrombolysis, and innate immune responses. In the present study, two full-length sequences encoding SERPIN were identified from metacercaria cDNA library of Clonorchis sinensis (C. sinensis) and were denominated as CsSERPIN and CsSERPIN3, respectively. Bioinformatics analysis showed that the two sequences shares 35.9% identity to each other. Both of the sequences have SERPIN domain and the greatest difference between the two domains is the reactive centre loop. Transmembrane region was found in CsSERPIN3 while not in CsSERPIN. The expression of the two CsSERPINs was significantly higher at the life stage of metacercaria than that of adult. The transcription levels of CsSERPIN and CsSERPIN3 at metacercaria stage were 3.249-and 11.314-fold of that at adult stage, respectively. Furthermore, the expression of CsSERPIN was 4.32-fold of that of CsSERPIN3 at metacercaria stage. Immunobiochemistry revealed that CsERPIN was dispersed at subtegument and oral sucker of metacercaria, while CsSERPIN3 localized intensely in the tegument of metacercaria of C. sinensis inside of the cyst wall. All these indicated that the CsSERPINs play important roles at metacercaria stage of the parasite. CsSERPIN may take part in regulation of endogenous serine proteinase and CsSERPIN3 may be involved in immune evasion and be a potential candidate for vaccine and drug target for clonorchiasis.

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Characterization of a novel vaccine candidate and serine proteinase inhibitor from Schistosoma japonicum (Sj serpin)

Cited by 37 publications

References 7 publications

Current Status of Vaccines for Schistosomiasis

Current Status of Vaccines for Schistosomiasis

Three-dimensional structure of a schistosome serpin revealing an unusual configuration of the helical subdomain

Comparison of two serpins ofClonorchis sinensisby bioinformatics, expression, and localization in metacercaria

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