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Foxp3 Silencing with Antisense Oligonucleotide Improves Immunogenicity of an Adjuvanted Recombinant Vaccine against Sporothrix schenckii

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Foxp3 Silencing with Antisense Oligonucleotide Improves Immunogenicity of an Adjuvanted Recombinant Vaccine against Sporothrix schenckii

dc.contributor.author	Batista-Duharte, Alexander
dc.contributor.author	Sendra Gisbert, Luis
dc.contributor.author	Herrero Cervera, María José
dc.contributor.author	Portuondo, Deivys Leandro
dc.contributor.author	Téllez-Martínez, Damiana
dc.contributor.author	Olivera, Gladys
dc.contributor.author	Fernández-Delgado, Manuel
dc.contributor.author	Javega, Beatriz
dc.contributor.author	Herrera Martín, Guadalupe
dc.contributor.author	Martínez-Romero, Alicia
dc.contributor.author	Costa, Paulo Inacio
dc.contributor.author	Zeppone Carlos, Iracilda
dc.contributor.author	Aliño Pellicer, Salvador F.
dc.date.accessioned	2022-05-18T14:22:54Z
dc.date.available	2022-05-18T14:22:54Z
dc.date.issued	2021
dc.identifier.citation	Batista-Duharte, Alexander Sendra Gisbert, Luis Herrero Cervera, María José Portuondo, Deivys Leandro Téllez-Martínez, Damiana Olivera, Gladys Fernández-Delgado, Manuel Javega, Beatriz Herrera Martín, Guadalupe Martínez-Romero, Alicia Costa, Paulo Inacio Zeppone Carlos, Iracilda Aliño Pellicer, Salvador F. 2021 Foxp3 Silencing with Antisense Oligonucleotide Improves Immunogenicity of an Adjuvanted Recombinant Vaccine against Sporothrix schenckii International Journal Of Molecular Sciences 22 7 3470
dc.identifier.uri	https://hdl.handle.net/10550/82833
dc.description.abstract	Background: In recent years, there has been great interest in developing molecular adjuvants based on antisense oligonucleotides (ASOs) targeting immunosuppressor pathways with inhibitory effects on regulatory T cells (Tregs) to improve immunogenicity and vaccine efficacy. We aim to evaluate the immunostimulating effect of 2′OMe phosphorothioated Foxp3-targeted ASO in an antifungal adjuvanted recombinant vaccine. Methods: The uptake kinetics of Foxp3 ASO, its cytotoxicity and its ability to deplete Tregs were evaluated in murine splenocytes in vitro. Groups of mice were vaccinated with recombinant enolase (Eno) of Sporothix schenckii in Montanide Gel 01 adjuvant alone or in combination with either 1 µg or 8 µg of Foxp3 ASO. The titers of antigen-specific antibody in serum samples from vaccinated mice (male C57BL/6) were determined by ELISA (enzyme-linked immunosorbent assay). Cultured splenocytes from each group were activated in vitro with Eno and the levels of IFN-γ and IL-12 were also measured by ELISA. The results showed that the anti-Eno antibody titer was significantly higher upon addition of 8 µM Foxp3 ASO in the vaccine formulation compared to the standard vaccine without ASO. In vitro and in vivo experiments suggest that Foxp3 ASO enhances specific immune responses by means of Treg depletion during vaccination. Conclusion: Foxp3 ASO significantly enhances immune responses against co-delivered adjuvanted recombinant Eno vaccine and it has the potential to improve vaccine immunogenicity.
dc.language.iso	eng
dc.relation.ispartof	International Journal Of Molecular Sciences, 2021, vol. 22, num. 7, p. 3470
dc.subject	Vacunació
dc.subject	Àcids nucleics
dc.subject	Fongs patògens
dc.subject	Farmacologia
dc.title	Foxp3 Silencing with Antisense Oligonucleotide Improves Immunogenicity of an Adjuvanted Recombinant Vaccine against Sporothrix schenckii
dc.type	journal article	es_ES
dc.date.updated	2022-05-18T14:22:54Z
dc.identifier.doi	10.3390/ijms22073470
dc.identifier.idgrec	152195
dc.rights.accessRights	open access	es_ES