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

Author(s):Show less -

Batista-Duharte, Alexander ^[1] ; Sendra, Luis ^{[2, 3]} ; Herrero, Maria Jose ^{[2, 3]} ; Portuondo, Deivys Leandro ^[1] ; Tellez-Martinez, Damiana ^[1] ; Olivera, Gladys ^[3] ; Fernandez-Delgado, Manuel ^[4] ; Javega, Beatriz ^[5] ; Herrera, Guadalupe ^[2] ; Martinez, Alicia ^[6] ; Costa, Paulo Inacio ^[1] ; Zeppone Carlos, Iracilda ^[1] ; Alino, Salvador Francisco ^{[2, 3, 7]}

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Clin Anal, BR-14800903 Araraquara, SP - Brazil

^[2] Univ Valencia, Fac Med, Pharmacol Dept, Valencia 46010 - Spain

^[3] Inst Invest Sanitaria La Fe, Pharmacogenet Unit, Valencia 46026 - Spain

^[4] Hosp Gen Univ Castellon, Serv Hematol & Hemotherapy, Castellon de La Plana 12004 - Spain

^[5] Univ Valencia, Fac Med, Cytometry Unit, Valencia 46010 - Spain

^[6] Ctr Invest Principe Felipe, Cytom Unit, Valencia 46012 - Spain

^[7] Hosp Univ Politecn La Fe, Med Clin Area, Unit Clin Pharmacol, Valencia 46026 - Spain

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 7 APR 2021.
• Web of Science Citations: 1

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 mu g or 8 mu g 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-gamma and IL-12 were also measured by ELISA. The results showed that the anti-Eno antibody titer was significantly higher upon addition of 8 mu M 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. (AU)

• FAPESP's process: 18/15187-2 - Effect of Foxp3 silencing on immunogenicity of vaccines against Sporothrix schenckii
• Grantee: Alexander Batista Duharte
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor