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Development of a vaccine against Fasciola hepatica based on the use of bioinformatics tools
15th National Programme for the allocation of Research Grants for Life and Matter Sciences
Rare diseases
Research Centre or Institution : Centro de Investigación de Enfermedades Tropicales de la Universidad de Salamanca (CIETUS)
Abstract
Currently there are no adequate controls against the infection caused by Fasciola hepatica. The resistance to drugs of choice, the lack of effective and environmentally safe molluscicides and the still low level of protection with the vaccines tested all raise the need for new prevention strategies. Although the Fasciola hepatica genome is still unknown, over recent years more than 200 cDNA sequences and their corresponding recombinant proteins have been described and scored. Based on current powerful bioinformatics tools, the project aims to design a rational strategy to identify peptides derived from the known sequences of F. hepatica.
These peptides were tested in combination with immunomodulators and modern and effective adjuvants, selected by the research group in previous projects. To carry out this project the following objectives are proposed: (i) Selection of genes using bioinformatics tools from molecules released from F. hepatica showing signal peptide and transmembrane domain; (ii) Identification of peptides from the previously selected sequences of the conserved regions containing B, T epitopes and catalytic sites; (iii) Synthesis of previously selected peptides; (iv) Assessment of immunological response induced by peptides in combination with new immunomodulators and adjuvants; (v) Selection of interim peptides using antibody-mediated cellular cytotoxicity methods; (vi) Study of vaccine peptides using in vivo vaccination trials in experimental fasciolosis models; (vii) Establishment of the response to Fasciola hepatica infection in animal models using Transcriptome analysis and (viii) Analysis of the effect of the vaccine and metabolic pathways.
The project has achieved the first four goals, and is in the process of analysis and elaboration of the results.
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