14CONFAP Application of quantitative proteomics to accelerate vaccine development against Schistosomiasis, a neglected tropical disease.

Schistosomiasis a neglected tropical disease caused by persistent blood-dwelling parasitic worms, is the focus of this application and remains an important public health problem in Brazil. Treatment with the one available drug does not prevent reinfection so an effective vaccine would enhance control. Sequencing of the worm's transcriptome (2003) and genome (2009) has facilitated post-genomic initiatives. Brazilian science would greatly benefit from an injection of cutting-edge proteomic technologies from UK experts to better orientate the search for novel vaccine candidates. As stated above previous collaborations between the proposed partners have led to publications in high impact journals, which in turn have informed the research of vaccinologists in Brazil and worldwide.

Proteomics is a young subject, expanding into a very sophisticated technology with enormous potential to illuminate many of the disease problems we face in the developed and developing world alike. The group in Ouro Preto is also in the growth phase. The proposed project could serve as the springboard to establish a longer-lasting collaboration with a leading group of UK researchers at the cutting edge of Proteomics. The impact that this would have on infectious tropical disease research in Brazil cannot be underestimated. The new collaboration will inject advanced proteomic techniques to underpin and consolidate the inventory of novel proteins we expect to identify and quantitate. We anticipate that the collaboration will kick-start a new round of vaccine testing.

In this programme, we will apply technologies developed at Liverpool to the analysis of potential vaccine candidates. In particular, Liverpool will host scientists and trainees from Ouro Preto, giving them access the super facilities that are located there. In addition, scientists from Liverpool will visit Ouro Preto to provide advanced training and to deliver a formal training course that will be open to other Brazilian scientists.

Mature 1 cm long schistosome worms feed exclusively on blood, the female consuming >four times her body volume per day, [1]. The blind ending alimentary tract comprises an oral cavity, a short esophagus and the gut where digestion and absorption take place. Much is known about gut processes but the esophagus has been viewed simply as a conducting tube. In collaborative research with York and Shanghai we have recently shown that the esophagus actually plays a pivotal role in the initial processing of ingested blood [2]. Erythrocytes are lysed as they pass through, whilst leukocytes become tethered to form a plug in which they are damaged and destroyed. Furthermore, the posterior region of the esophagus is surrounded by a gland from which proteins secreted into the lumen facilitate these biological processes. A major focus of our research is to identify the secreted components, establish their functions and discover which are promising targets for a vaccine. Genes expressed in the posterior esophageal region have been identified by collaborators using in-situ hybridization [3, 4], microarray analysis of gene expression [5] and most recently subtractive RNA-Seq [6]. As a result we have a list of ~30 genes encoding secreted proteins, with expression localized exclusively or predominantly to the posterior esophagus. We have also shown that the anterior esophageal compartment is a secretory organ releasing the contents of distinct vesicles into the esophageal lumen [7]. Independently, expression of MEG-12 has been demonstrated in the anterior esophagus and its protein products shown to destabilize erythrocyte membranes [8]. Lastly, we have shown that in vivo, host antibodies bind to secreted proteins of both esophageal compartments, confirming that these proteins might serve as vaccine candidates.

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