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The Schistosoma mansoni cyclophilin A epitope 107-121 induces a protective immune response against schistosomiasis.
de Melo, Tatiane Teixeira; Mendes, Mariana Moreira; Alves, Clarice Carvalho; Carvalho, Gardênia Braz; Fernandes, Viviane Cristina; Pimenta, Deborah Laranjeira Ferreira; de Moraes Mourão, Marina; Gai, Fatou; Kalli, Marina; Coelho, Aline; de Azambuja Ribeiro, Rosy Iara Maciel; Falcone, Franco H; Pereira, Rosiane Aparecida da Silva; Fonseca, Cristina Toscano.
Afiliación
  • de Melo TT; Laboratório de Biologia e Imunologia de Doenças Infeciosas e Parasitárias, Instituto René Rachou, Fiocruz-MG, Belo Horizonte, Minas Gerais, Brazil.
  • Mendes MM; Laboratório de Biologia e Imunologia de Doenças Infeciosas e Parasitárias, Instituto René Rachou, Fiocruz-MG, Belo Horizonte, Minas Gerais, Brazil.
  • Alves CC; Laboratório de Biologia e Imunologia de Doenças Infeciosas e Parasitárias, Instituto René Rachou, Fiocruz-MG, Belo Horizonte, Minas Gerais, Brazil.
  • Carvalho GB; Laboratório de Biologia e Imunologia de Doenças Infeciosas e Parasitárias, Instituto René Rachou, Fiocruz-MG, Belo Horizonte, Minas Gerais, Brazil.
  • Fernandes VC; Laboratório de Biologia e Imunologia de Doenças Infeciosas e Parasitárias, Instituto René Rachou, Fiocruz-MG, Belo Horizonte, Minas Gerais, Brazil.
  • Pimenta DLF; Laboratório de Biologia e Imunologia de Doenças Infeciosas e Parasitárias, Instituto René Rachou, Fiocruz-MG, Belo Horizonte, Minas Gerais, Brazil.
  • de Moraes Mourão M; Laboratório de Helmintologia e Malacologia Médica, Instituto René Rachou, Fiocruz-MG, Belo Horizonte, Minas Gerais, Brazil.
  • Gai F; The School of Pharmacy, University of Nottingham, Nottingham, United Kingdom.
  • Kalli M; The School of Pharmacy, University of Nottingham, Nottingham, United Kingdom.
  • Coelho A; Laboratório de Patologia Experimental, Universidade Federal De São João Del Rei- Campus Divinópolis, Minas Gerais, Brazil.
  • de Azambuja Ribeiro RIM; Laboratório de Patologia Experimental, Universidade Federal De São João Del Rei- Campus Divinópolis, Minas Gerais, Brazil.
  • Falcone FH; The School of Pharmacy, University of Nottingham, Nottingham, United Kingdom.
  • Pereira RADS; Laboratório de Biologia e Imunologia de Doenças Infeciosas e Parasitárias, Instituto René Rachou, Fiocruz-MG, Belo Horizonte, Minas Gerais, Brazil.
  • Fonseca CT; Laboratório de Biologia e Imunologia de Doenças Infeciosas e Parasitárias, Instituto René Rachou, Fiocruz-MG, Belo Horizonte, Minas Gerais, Brazil. Electronic address: cristina.toscano@fiocruz.br.
Mol Immunol ; 111: 172-181, 2019 07.
Article en En | MEDLINE | ID: mdl-31063938
Great efforts have been made to identify promising antigens and vaccine formulations against schistosomiasis. Among the previously described Schistosoma vaccine candidates, cyclophilins comprise an interesting antigen that could be used for vaccine formulations. Cyclophilin A is the target for the cyclosporine A, a drug with schistosomicide activity, and its orthologue from Schistosoma japonicum induces a protective immune response in mice. Although Schistosoma mansoni cyclophilin A also represents a promising target for anti-schistosome vaccines, its potential to induce protection has not been evaluated. In this study, we characterized the cyclophilin A (SmCyp), initially described as Smp17.7, analyzed its allergenic potential using in vitro functional assays, and evaluated its ability to induce protection in mice when administered as an antigen using different vaccine formulations and strategies. Results indicated that SmCyp could be successfully expressed by mammalian cells and bacteria. The recombinant protein did not promote IgE-reporter system activation in vitro, demonstrating its probable safety for use in vaccine formulations. T and B-cell epitopes were predicted in the SmCyp sequence, with two of them located within the active isomerase site. The most immunogenic antigen, SmCyp (107-121), was then used for immunization protocols. Immunization with the SmCyp gene or protein failed to reduce parasite burden but induced an immune response that modulated the granuloma area. In contrast, immunization with the synthetic peptide SmCyp (107-121) significantly reduced worm burden (48-50%) in comparison to control group, but did not regulate liver pathology. Moreover, the protection observed in mice immunized with the synthetic peptide was associated with the significant production of antibodies against the SmCyp (107-121) epitope. Therefore, in this study, we identified an epitope within the SmCyp sequence that induces a protective immune response against the parasite, thus representing a promising antigen that could be used for vaccine formulation against schistosomiasis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Schistosoma mansoni / Esquistosomiasis mansoni / Ciclofilina A / Epítopos Límite: Animals Idioma: En Revista: Mol Immunol Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Schistosoma mansoni / Esquistosomiasis mansoni / Ciclofilina A / Epítopos Límite: Animals Idioma: En Revista: Mol Immunol Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido