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Experimental and Theoretical Approaches To Investigate the Immunogenicity of Taenia solium-Derived KE7 Antigen

cysticercosis, a parasitic disease that affects human health in various regions of the world, is preventable by vaccination. Both the 97-amino-acid-long KETc7 peptide and its carboxyl-terminal, 18-amino-acid-long sequence (GK-1) are found in Both peptides have proven protective capacity against cyst...

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Published in:Infection and immunity 2017-12, Vol.85 (12)
Main Authors: Bobes, Raúl J, Navarrete-Perea, José, Ochoa-Leyva, Adrián, Anaya, Víctor Hugo, Hernández, Marisela, Cervantes-Torres, Jacquelynne, Estrada, Karel, Sánchez-Lopez, Filiberto, Soberón, Xavier, Rosas, Gabriela, Nunes, Cáris Maroni, García-Varela, Martín, Sotelo-Mundo, Rogerio Rafael, López-Zavala, Alonso Alexis, Gevorkian, Goar, Acero, Gonzalo, Laclette, Juan P, Fragoso, Gladis, Sciutto, Edda
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Language:English
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Summary:cysticercosis, a parasitic disease that affects human health in various regions of the world, is preventable by vaccination. Both the 97-amino-acid-long KETc7 peptide and its carboxyl-terminal, 18-amino-acid-long sequence (GK-1) are found in Both peptides have proven protective capacity against cysticercosis and are part of the highly conserved, cestode-native, 264-amino-acid long protein KE7. KE7 belongs to a ubiquitously distributed family of proteins associated with membrane processes and may participate in several vital cell pathways. The aim of this study was to identify the KE7 (TsKE7) full-length protein and to determine its immunogenic properties. Recombinant TsKE7 (rTsKE7) was expressed in Rosetta2 cells and used to obtain mouse polyclonal antibodies. Anti-rTsKE7 antibodies detected the expected native protein among the 350 spots developed from cyst vesicular fluid in a mass spectrometry-coupled immune proteomic analysis. These antibodies were then used to screen a phage-displayed 7-random-peptide library to map B-cell epitopes. The recognized phages displayed 9 peptides, with the consensus motif Y(F/Y)PS sequence, which includes YYYPS (named GK-1M, for being a GK-1 mimotope), exactly matching a part of GK-1. GK-1M was recognized by 58% of serum samples from cysticercotic pigs with 100% specificity but induced weak protection against murine cysticercosis. analysis revealed a universal T-cell epitope(s) in native TsKE7 potentially capable of stimulating cytotoxic T lymphocytes and helper T lymphocytes under different major histocompatibility complex class I and class II mouse haplotypes. Altogether, these results provide a rationale for the efficacy of the KETc7, rTsKE7, and GK-1 peptides as vaccines.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.00395-17