Foxp3 silencing with antisense oligonucleotide improves immunogenicity of an adjuvanted recombinant vaccine against sporothrix schenckii

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dc.contributor.authorBatista-Duharte, Alexander [UNESP]
dc.contributor.authorSendra, Luis
dc.contributor.authorHerrero, Maria José
dc.contributor.authorPortuondo, Deivys Leandro [UNESP]
dc.contributor.authorTéllez-Martínez, Damiana [UNESP]
dc.contributor.authorOlivera, Gladys
dc.contributor.authorFernández-Delgado, Manuel
dc.contributor.authorJavega, Beatriz
dc.contributor.authorHerrera, Guadalupe
dc.contributor.authorMartínez, Alicia
dc.contributor.authorCosta, Paulo Inacio [UNESP]
dc.contributor.authorCarlos, Iracilda Zeppone [UNESP]
dc.contributor.authorAliño, Salvador Francisco
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversitat de Valencia
dc.contributor.institutionInstituto de Investigación Sanitaria La Fe
dc.contributor.institutionHospital General Universitario de Castellón
dc.contributor.institutionCentro de Investigación Príncipe Felipe
dc.contributor.institutionHospital Universitario y Politécnico La Fe
dc.date.accessioned2021-06-25T10:56:14Z
dc.date.available2021-06-25T10:56:14Z
dc.date.issued2021-04-01
dc.description.abstractBackground: 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 cyto-toxicity 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.en
dc.description.affiliationDepartment of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University (UNESP)
dc.description.affiliationPharmacology Department Faculty of Medicine Universitat de Valencia
dc.description.affiliationPharmacogenetics Unit Instituto de Investigación Sanitaria La Fe
dc.description.affiliationService of Hematology and Hemotherapy Hospital General Universitario de Castellón
dc.description.affiliationCytometry Unit Faculty of Medicine Universitat de Valencia
dc.description.affiliationCytomics Unit Centro de Investigación Príncipe Felipe
dc.description.affiliationUnit of Clinical Pharmacology Medicine Clinical Area Hospital Universitario y Politécnico La Fe
dc.description.affiliationUnespDepartment of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University (UNESP)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 2018/15187-2
dc.identifierhttp://dx.doi.org/10.3390/ijms22073470
dc.identifier.citationInternational Journal of Molecular Sciences, v. 22, n. 7, 2021.
dc.identifier.doi10.3390/ijms22073470
dc.identifier.issn1422-0067
dc.identifier.issn1661-6596
dc.identifier.scopus2-s2.0-85103006667
dc.identifier.urihttp://hdl.handle.net/11449/207498
dc.language.isoeng
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.sourceScopus
dc.subjectAntisensense oligonucleotide
dc.subjectFoxp3
dc.subjectRegulatory T cells
dc.subjectSporothrix schenckii
dc.subjectVaccine immunogenicity
dc.titleFoxp3 silencing with antisense oligonucleotide improves immunogenicity of an adjuvanted recombinant vaccine against sporothrix schenckiien
dc.typeArtigo

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