A Vaccine Based on Kunitz-Type Molecule Confers Protection Against <i>Fasciola hepatica</i> Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production

Autores
Silvane, Leonardo Micael; Celias, Daiana Pamela; Romagnoli, Pablo Alberto; Maletto, Belkys Angélica; Sánchez Vallecillo, María Fernanda; Chiapello, Laura Silvina; Palma, Santiago Daniel; Allemandi, Daniel Alberto; Sanabria, Rodrigo Eduardo Fabrizio; Pruzzo, César Iván; Motrán, Claudia Cristina; Cervi, Laura
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fasciola hepatica is helminth parasite found around the world that causes fasciolosis, a chronic disease affecting mainly cattle, sheep, and occasionally humans. Triclabendazole is the drug of choice to treat this parasite. However, the continuous use of this drug has led to the development of parasite resistance and, consequently, the limitation of its effectiveness. Hence, vaccination appears as an attractive option to develop. In this work, we evaluated the potential of F. hepatica Kunitz-type molecule (FhKTM) as an antigen formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate ester (Coa-ASC16) and the synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) during an experimental model of fasciolosis in mice, and we further dissected the immune response associated with host protection. Our results showed that immunization of mice with FhKTM/CpG-ODN/Coa-ASC16 induces protection against F. hepatica challenge by preventing liver damage and improving survival after F. hepatica infection. FhKTM/CpG-ODN/Coa-ASC16-immunized mice elicited potent IFN-γ and IL-17A with high levels of antigen-specific IgG1, IgG2a, and IgA serum antibodies. Strikingly, IL-17A blockade during infection decreased IgG2a and IgA antibody levels as well as IFN-γ production, leading to an increase in mortality of vaccinated mice. The present study highlights the potential of a new vaccine formulation to improve control and help the eradication of F. hepatica infection, with potential applications for natural hosts such as cattle and sheep.
Facultad de Ciencias Veterinarias
Materia
Ciencias Médicas
Ciencias Exactas
Veterinaria
Th17-dependent protection
nanostructure
ascorbyl palmitate
kunitz type molecule
vaccine
Fasciola hepatica
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/124518

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oai_identifier_str oai:sedici.unlp.edu.ar:10915/124518
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling A Vaccine Based on Kunitz-Type Molecule Confers Protection Against <i>Fasciola hepatica</i> Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A ProductionSilvane, Leonardo MicaelCelias, Daiana PamelaRomagnoli, Pablo AlbertoMaletto, Belkys AngélicaSánchez Vallecillo, María FernandaChiapello, Laura SilvinaPalma, Santiago DanielAllemandi, Daniel AlbertoSanabria, Rodrigo Eduardo FabrizioPruzzo, César IvánMotrán, Claudia CristinaCervi, LauraCiencias MédicasCiencias ExactasVeterinariaTh17-dependent protectionnanostructureascorbyl palmitatekunitz type moleculevaccineFasciola hepatica<i>Fasciola hepatica</i> is helminth parasite found around the world that causes fasciolosis, a chronic disease affecting mainly cattle, sheep, and occasionally humans. Triclabendazole is the drug of choice to treat this parasite. However, the continuous use of this drug has led to the development of parasite resistance and, consequently, the limitation of its effectiveness. Hence, vaccination appears as an attractive option to develop. In this work, we evaluated the potential of <i>F. hepatica</i> Kunitz-type molecule (FhKTM) as an antigen formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate ester (Coa-ASC16) and the synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) during an experimental model of fasciolosis in mice, and we further dissected the immune response associated with host protection. Our results showed that immunization of mice with FhKTM/CpG-ODN/Coa-ASC16 induces protection against <i>F. hepatica</i> challenge by preventing liver damage and improving survival after <i>F. hepatica</i> infection. FhKTM/CpG-ODN/Coa-ASC16-immunized mice elicited potent IFN-γ and IL-17A with high levels of antigen-specific IgG1, IgG2a, and IgA serum antibodies. Strikingly, IL-17A blockade during infection decreased IgG2a and IgA antibody levels as well as IFN-γ production, leading to an increase in mortality of vaccinated mice. The present study highlights the potential of a new vaccine formulation to improve control and help the eradication of <i>F. hepatica</i> infection, with potential applications for natural hosts such as cattle and sheep.Facultad de Ciencias Veterinarias2020-10-20info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/124518enginfo:eu-repo/semantics/altIdentifier/issn/1664-3224info:eu-repo/semantics/altIdentifier/pmid/33193292info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2020.02087info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-03T11:01:54Zoai:sedici.unlp.edu.ar:10915/124518Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-03 11:01:54.889SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv A Vaccine Based on Kunitz-Type Molecule Confers Protection Against <i>Fasciola hepatica</i> Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production
title A Vaccine Based on Kunitz-Type Molecule Confers Protection Against <i>Fasciola hepatica</i> Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production
spellingShingle A Vaccine Based on Kunitz-Type Molecule Confers Protection Against <i>Fasciola hepatica</i> Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production
Silvane, Leonardo Micael
Ciencias Médicas
Ciencias Exactas
Veterinaria
Th17-dependent protection
nanostructure
ascorbyl palmitate
kunitz type molecule
vaccine
Fasciola hepatica
title_short A Vaccine Based on Kunitz-Type Molecule Confers Protection Against <i>Fasciola hepatica</i> Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production
title_full A Vaccine Based on Kunitz-Type Molecule Confers Protection Against <i>Fasciola hepatica</i> Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production
title_fullStr A Vaccine Based on Kunitz-Type Molecule Confers Protection Against <i>Fasciola hepatica</i> Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production
title_full_unstemmed A Vaccine Based on Kunitz-Type Molecule Confers Protection Against <i>Fasciola hepatica</i> Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production
title_sort A Vaccine Based on Kunitz-Type Molecule Confers Protection Against <i>Fasciola hepatica</i> Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production
dc.creator.none.fl_str_mv Silvane, Leonardo Micael
Celias, Daiana Pamela
Romagnoli, Pablo Alberto
Maletto, Belkys Angélica
Sánchez Vallecillo, María Fernanda
Chiapello, Laura Silvina
Palma, Santiago Daniel
Allemandi, Daniel Alberto
Sanabria, Rodrigo Eduardo Fabrizio
Pruzzo, César Iván
Motrán, Claudia Cristina
Cervi, Laura
author Silvane, Leonardo Micael
author_facet Silvane, Leonardo Micael
Celias, Daiana Pamela
Romagnoli, Pablo Alberto
Maletto, Belkys Angélica
Sánchez Vallecillo, María Fernanda
Chiapello, Laura Silvina
Palma, Santiago Daniel
Allemandi, Daniel Alberto
Sanabria, Rodrigo Eduardo Fabrizio
Pruzzo, César Iván
Motrán, Claudia Cristina
Cervi, Laura
author_role author
author2 Celias, Daiana Pamela
Romagnoli, Pablo Alberto
Maletto, Belkys Angélica
Sánchez Vallecillo, María Fernanda
Chiapello, Laura Silvina
Palma, Santiago Daniel
Allemandi, Daniel Alberto
Sanabria, Rodrigo Eduardo Fabrizio
Pruzzo, César Iván
Motrán, Claudia Cristina
Cervi, Laura
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
Ciencias Exactas
Veterinaria
Th17-dependent protection
nanostructure
ascorbyl palmitate
kunitz type molecule
vaccine
Fasciola hepatica
topic Ciencias Médicas
Ciencias Exactas
Veterinaria
Th17-dependent protection
nanostructure
ascorbyl palmitate
kunitz type molecule
vaccine
Fasciola hepatica
dc.description.none.fl_txt_mv <i>Fasciola hepatica</i> is helminth parasite found around the world that causes fasciolosis, a chronic disease affecting mainly cattle, sheep, and occasionally humans. Triclabendazole is the drug of choice to treat this parasite. However, the continuous use of this drug has led to the development of parasite resistance and, consequently, the limitation of its effectiveness. Hence, vaccination appears as an attractive option to develop. In this work, we evaluated the potential of <i>F. hepatica</i> Kunitz-type molecule (FhKTM) as an antigen formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate ester (Coa-ASC16) and the synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) during an experimental model of fasciolosis in mice, and we further dissected the immune response associated with host protection. Our results showed that immunization of mice with FhKTM/CpG-ODN/Coa-ASC16 induces protection against <i>F. hepatica</i> challenge by preventing liver damage and improving survival after <i>F. hepatica</i> infection. FhKTM/CpG-ODN/Coa-ASC16-immunized mice elicited potent IFN-γ and IL-17A with high levels of antigen-specific IgG1, IgG2a, and IgA serum antibodies. Strikingly, IL-17A blockade during infection decreased IgG2a and IgA antibody levels as well as IFN-γ production, leading to an increase in mortality of vaccinated mice. The present study highlights the potential of a new vaccine formulation to improve control and help the eradication of <i>F. hepatica</i> infection, with potential applications for natural hosts such as cattle and sheep.
Facultad de Ciencias Veterinarias
description <i>Fasciola hepatica</i> is helminth parasite found around the world that causes fasciolosis, a chronic disease affecting mainly cattle, sheep, and occasionally humans. Triclabendazole is the drug of choice to treat this parasite. However, the continuous use of this drug has led to the development of parasite resistance and, consequently, the limitation of its effectiveness. Hence, vaccination appears as an attractive option to develop. In this work, we evaluated the potential of <i>F. hepatica</i> Kunitz-type molecule (FhKTM) as an antigen formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate ester (Coa-ASC16) and the synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) during an experimental model of fasciolosis in mice, and we further dissected the immune response associated with host protection. Our results showed that immunization of mice with FhKTM/CpG-ODN/Coa-ASC16 induces protection against <i>F. hepatica</i> challenge by preventing liver damage and improving survival after <i>F. hepatica</i> infection. FhKTM/CpG-ODN/Coa-ASC16-immunized mice elicited potent IFN-γ and IL-17A with high levels of antigen-specific IgG1, IgG2a, and IgA serum antibodies. Strikingly, IL-17A blockade during infection decreased IgG2a and IgA antibody levels as well as IFN-γ production, leading to an increase in mortality of vaccinated mice. The present study highlights the potential of a new vaccine formulation to improve control and help the eradication of <i>F. hepatica</i> infection, with potential applications for natural hosts such as cattle and sheep.
publishDate 2020
dc.date.none.fl_str_mv 2020-10-20
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/124518
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dc.language.none.fl_str_mv eng
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info:eu-repo/semantics/altIdentifier/pmid/33193292
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2020.02087
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
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reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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