A Vaccine Based on Kunitz-Type Molecule Confers Protection Against Fasciola hepatica Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production
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 paras...
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.02087/full |
| _version_ | 1818118411325014016 |
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| author | Leonardo Silvane Leonardo Silvane Daiana Pamela Celias Daiana Pamela Celias Pablo Alberto Romagnoli Pablo Alberto Romagnoli Belkys Angélica Maletto Belkys Angélica Maletto María Fernanda Sanchez Vallecillo María Fernanda Sanchez Vallecillo Laura Silvina Chiapello Laura Silvina Chiapello Santiago Daniel Palma Santiago Daniel Palma Daniel Alberto Allemandi Daniel Alberto Allemandi Rodrigo Eduardo Fabrizio Sanabria Rodrigo Eduardo Fabrizio Sanabria César Iván Pruzzo Claudia Cristina Motrán Claudia Cristina Motrán Laura Cervi Laura Cervi |
| author_facet | Leonardo Silvane Leonardo Silvane Daiana Pamela Celias Daiana Pamela Celias Pablo Alberto Romagnoli Pablo Alberto Romagnoli Belkys Angélica Maletto Belkys Angélica Maletto María Fernanda Sanchez Vallecillo María Fernanda Sanchez Vallecillo Laura Silvina Chiapello Laura Silvina Chiapello Santiago Daniel Palma Santiago Daniel Palma Daniel Alberto Allemandi Daniel Alberto Allemandi Rodrigo Eduardo Fabrizio Sanabria Rodrigo Eduardo Fabrizio Sanabria César Iván Pruzzo Claudia Cristina Motrán Claudia Cristina Motrán Laura Cervi Laura Cervi |
| author_sort | Leonardo Silvane |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T04:53:53Z |
| format | Article |
| id | doaj.art-b2a69e3c3bb94c1499284ee3dd3e3ade |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T04:53:53Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b2a69e3c3bb94c1499284ee3dd3e3ade2022-12-22T01:20:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-10-011110.3389/fimmu.2020.02087549651A Vaccine Based on Kunitz-Type Molecule Confers Protection Against Fasciola hepatica Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A ProductionLeonardo Silvane0Leonardo Silvane1Daiana Pamela Celias2Daiana Pamela Celias3Pablo Alberto Romagnoli4Pablo Alberto Romagnoli5Belkys Angélica Maletto6Belkys Angélica Maletto7María Fernanda Sanchez Vallecillo8María Fernanda Sanchez Vallecillo9Laura Silvina Chiapello10Laura Silvina Chiapello11Santiago Daniel Palma12Santiago Daniel Palma13Daniel Alberto Allemandi14Daniel Alberto Allemandi15Rodrigo Eduardo Fabrizio Sanabria16Rodrigo Eduardo Fabrizio Sanabria17César Iván Pruzzo18Claudia Cristina Motrán19Claudia Cristina Motrán20Laura Cervi21Laura Cervi22Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, ArgentinaCentro de Investigación en Medicina Traslacional Severo Amuchastegui (CIMETSA), Córdoba, ArgentinaInstituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, ArgentinaDepartamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaUnidad de Investigación y desarrollo en Tecnología Farmacéutica (UNITEFA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, ArgentinaDepartamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaUnidad de Investigación y desarrollo en Tecnología Farmacéutica (UNITEFA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, ArgentinaFacultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, ArgentinaInstituto Tecnológico Chascomús (INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de San Martín (CONICET/UNSAM), Chascomús, ArgentinaFacultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, ArgentinaFasciola 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.https://www.frontiersin.org/articles/10.3389/fimmu.2020.02087/fullTh17-dependent protectionnanostructureascorbyl palmitatekunitz type moleculevaccineFasciola hepatica |
| spellingShingle | Leonardo Silvane Leonardo Silvane Daiana Pamela Celias Daiana Pamela Celias Pablo Alberto Romagnoli Pablo Alberto Romagnoli Belkys Angélica Maletto Belkys Angélica Maletto María Fernanda Sanchez Vallecillo María Fernanda Sanchez Vallecillo Laura Silvina Chiapello Laura Silvina Chiapello Santiago Daniel Palma Santiago Daniel Palma Daniel Alberto Allemandi Daniel Alberto Allemandi Rodrigo Eduardo Fabrizio Sanabria Rodrigo Eduardo Fabrizio Sanabria César Iván Pruzzo Claudia Cristina Motrán Claudia Cristina Motrán Laura Cervi Laura Cervi A Vaccine Based on Kunitz-Type Molecule Confers Protection Against Fasciola hepatica Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production Frontiers in Immunology Th17-dependent protection nanostructure ascorbyl palmitate kunitz type molecule vaccine Fasciola hepatica |
| title | A Vaccine Based on Kunitz-Type Molecule Confers Protection Against Fasciola hepatica 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 Fasciola hepatica 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 Fasciola hepatica 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 Fasciola hepatica Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production |
| title_short | A Vaccine Based on Kunitz-Type Molecule Confers Protection Against Fasciola hepatica Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production |
| title_sort | vaccine based on kunitz type molecule confers protection against fasciola hepatica challenge by inducing ifn γ and antibody immune responses through il 17a production |
| topic | Th17-dependent protection nanostructure ascorbyl palmitate kunitz type molecule vaccine Fasciola hepatica |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.02087/full |
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