Cellular responses to <i>Schistosoma japonicum</i> cathepsin D aspartic protease

Verity, Christiana K.; McManus, Donald P.; Brindley, Paul J.

doi:10.1046/j.1365-3024.2002.00475.x

Cited by 10 publications

(4 citation statements)

References 16 publications

(20 reference statements)

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“…By contrast, a significant reduction in IL-4 secretion was observed. Thus, we deduce that the pVIVO 2 SjFABP-23 DNA vaccine may induce a strong Th1 response and suppress Th2 immunity, which was to some extent similar to the results obtained by Zhang et al [13,33]. Previous studies showed that protection was conferred by Th1 cellular immunity with lymphoid proliferation in the region and mediastinal lymph nodes [34], elevated production of IgG4 and IgG2 antibodies, and inhibition of IgE consistently associated with increased susceptibility to reinfection [35].…”

Section: Discussionsupporting

confidence: 87%

Schistosoma japonicum: The design and experimental evaluation of a multivalent DNA vaccine

Li¹,

et al. 2006

Cellular and Molecular Biology Letters

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The aim of this study was to construct and evaluate the immunity efficacy of the DNA multivalent vaccine pVIVO 2 SjFABP-23. The vaccine was constructed and produced as follows. Forty BALB/c mice were divided into four groups designated pVIVO 2 , pVIVO 2 Sj23, pVIVO 2 SjFABP and pVIVO 2 SjFABP-23. Each mouse was immunized with 100 µg of the corresponding plasmid DNA by intramuscular injection. 28 days postvaccination, the mice were challenged with S. japonicum cercariae, and the worm and egg burdens were determined 42 days post-challenge. Serum samples were collected from all the mice before and after vaccination and at the end of the experiment, and used for antibody detection. The IFN-γ and IL-4 levels were quantified in the supernatants of specifically stimulated spleen cells. The number of worms was reduced by 52%, 40% and 42% in mice respectively immunized with pVIVO 2 SjFABP-23, pVIVO 2 Sj23 or pVIVO 2 SjFABP. A respective 61%, 38% and 39% egg reduction was determined relative to those mice that only received the empty pVIVO 2 plasmid. pVIVO 2 SjFABP-23 immunization increased IgG levels against SWAP and SEA. Increased IFN-γ levels were detected in the supernatant of specific stimulated spleen cells from mice immunized with the 3 different constructs. The multivalent DNA vaccine developed induced higher levels of protection than the two monovalent tested vaccines.

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Section: Discussionsupporting

confidence: 87%

Schistosoma japonicum: The design and experimental evaluation of a multivalent DNA vaccine

Li¹,

et al. 2006

Cellular and Molecular Biology Letters

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“…Immunization with the recombinant protein resulted in reduced worm burden in challenged mice but little to no effect in reducing the fecundity of the pathogen. The authors showed that the schistosome protease induced a mixed Th1/Th2 cytokine response (45). Immunization of C57BL/6 mice with recombinant Pep1 of C. posadasii induced a moderate in vitro proliferative response of isolated immune T cells in a recall experiment.…”

Section: Discussionmentioning

confidence: 99%

A Recombinant Aspartyl Protease ofCoccidioides posadasiiInduces Protection against Pulmonary Coccidioidomycosis in Mice

et al. 2006

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Coccidioidomycosis is a respiratory disease of humans caused by the desert soil-borne fungal pathogens Coccidioides spp. Recurrent epidemics of this mycosis in the southwestern United States have contributed significantly to escalated health care costs. Clinical and experimental studies indicate that prior symptomatic coccidioidomycosis induces immunity against subsequent infection, and activation of T cells is essential for containment of the pathogen and its clearance from host tissue. Development of a human vaccine against coccidioidomycosis has focused on recombinant T-cell-reactive antigens which elicit a durable protective immune response against pulmonary infection in mice. In this study we fractionated a protective multicomponent parasitic cell wall extract in an attempt to identify T-cell antigens. Immunoblots of electrophoretic separations of this extract identified patient seroreactive proteins which were subsequently excised from two-dimensional polyacrylamide gel electrophoresis gels, trypsin digested, and sequenced by tandem mass spectrometry. The full-length gene which encodes a dominant protein in the immunoblot was identified using established methods of bioinformatics. The gene was cloned and expressed, and the recombinant protein was shown to stimulate immune T cells in vitro. The deduced protein was predicted to contain epitopes that bind to human major histocompatibility complex class II molecules using a TEPITOPE-based algorithm. Synthetic peptides corresponding to the predicted T-cell epitopes induced gamma interferon production by immune T lymphocytes. The T-cell-reactive antigen, which is homologous to secreted fungal aspartyl proteases, protected mice against pulmonary infection with Coccidioides posadasii. We argue that this immunoproteomic/ bioinformatic approach to the identification of candidate vaccines against coccidioidomycosis is both efficient and productive.

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“…Mouse studies of bacterially expressed and purified recombinant Sj22·6 have demonstrated specific IgG and IgE production but no protection (51). In similar fashion, vaccination with E. coli and baculovirus‐expressed recombinant S. japonicum aspartic protease – cathepsin D – generated high levels of specific antibodies but only a limited level of protection (52–54). Encouraging results have been obtained with recombinant S. japonicum 26‐kDa glutathione S ‐transferase (GST), which induced a pronounced anti‐fecundity effect, as well as a moderate but significant level of protection in terms of reduced worm burden in mice (55), pigs (56) and buffalo (57,58) following experimental or natural challenge infection with S. japonicum .…”

Section: Vaccine Targetsmentioning

confidence: 99%

Prospects for development of a transmission blocking vaccine against Schistosoma japonicum

McManus

2005

Parasite Immunology

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Despite intensive long-term control programmes, schistosomiasis japonica remains a serious public health problem in China and the Philippines. The termination of mass praziquantel-treatment has seen a dramatic recent rebound in both its prevalence and associated morbidity. Schistosomiasis japonica is a zoonosis but, despite complicating control efforts, this feature provides a practical method for attacking Schistosoma japonicum through development and deployment of a transmission blocking veterinary vaccine. A recently completed bovine drug intervention trial and mathematical modelling of the transmission of S. japonicum underpin the concept that such a vaccine, targeting water buffalo, would have major implications for future integrated schistosomiasis control in China. A major block to success is the low ceiling efficacy achieved with current vaccine molecules. To solve this challenge, an antigen discovery pipeline needs to be established for identification of new vaccine targets that induce greater potency than the current anti-S. japonicum candidate vaccines. Excretory-secretory products and molecules exposed on epithelial surfaces (including receptors) which interact directly with the host immune system warrant especial attention. Extensive schistosome genomics programmes currently underway coupled with new advances in proteomics and microarray technology provide an unparalleled opportunity to identify new molecules exploitable as vaccine targets. These will then need to be produced in quantity and rigorously tested first in the laboratory and then the field. If a transmission blocking veterinary vaccine developed for bovines can be put into practice in combination with other control strategies such as human chemotherapy, elimination of S. japonicum from China may be achievable.

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Cellular responses to Schistosoma japonicum cathepsin D aspartic protease

Cited by 10 publications

References 16 publications

Schistosoma japonicum: The design and experimental evaluation of a multivalent DNA vaccine

Schistosoma japonicum: The design and experimental evaluation of a multivalent DNA vaccine

A Recombinant Aspartyl Protease ofCoccidioides posadasiiInduces Protection against Pulmonary Coccidioidomycosis in Mice

Prospects for development of a transmission blocking vaccine against Schistosoma japonicum

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