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

Laura Silvina Chiapello²  Leonardo Silvane²  Daiana Pamela Celias²  Claudia Cristina Motrán²  Belkys Angélica Maletto²  Laura Cervi²  María Fernanda Sanchez Vallecillo²  César Iván Pruzzo⁵  Rodrigo Eduardo Fabrizio Sanabria⁶  Pablo Alberto Romagnoli⁷  Santiago Daniel Palma⁸  Daniel Alberto Allemandi⁸ 

[1] Centro de Investigación en Medicina Traslacional Severo Amuchastegui (CIMETSA), Córdoba, Argentina;Centro de investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina;Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina;Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina;Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina;Instituto Tecnológico Chascomús (INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de San Martín (CONICET/UNSAM), Chascomús, Argentina;Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina;Unidad de Investigación y desarrollo en Tecnología Farmacéutica (UNITEFA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina;

关键词: Th17-dependent protection;    nanostructure;    ascorbyl palmitate;    kunitz type molecule;    vaccine;    Fasciola hepatica;   

DOI  :  10.3389/fimmu.2020.02087

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown