"Evaluation of the immunomodulatory effect of an anti-CTLA4 oligonucleotide in formulation with a recombinant vaccine candidate against sporotrichosis"

Abstract

Sporotrichosis is endemic in Latin America and hyperendemic in Brazil, where for more than two decades has been presented as zoonosis transmitted by cats infected with the fungus Sporothrix brasiliensis. Regulatory CD4+ T cells characterized by the expression of molecules CD25, FOXP3 and CTLA-4 are responsible for efficacy of self-tolerance mechanisms and regulation of immune response estimulated by pathogens and vaccine formulations. Studies have been demonstrated that the blocking strategy of molecules FOXP3 and CTLA-4 improves the immunogenicity of vaccines. Among these strategies there are oligonucleotides (ASOs) or single-stranded DNA that bind in a complementary way to the target mRNA, stimulating the blockade of translation of this gene and, consequently, protein expression. Recently, we demonstrated that recombinant Sporothrix spp protein enolase (rSsEno), formulated with the adjuvant Gel01 and anti-FOXP3 ASO, stimulates a higher antigen-specific antibody response than exclusive adjuvanted formulation with Gel01. In this project, we propose to evaluate whether the rSsEno+Gel01 formulation induces the same immunogenic response in formulation with an anti-CTLA4 ASO in mice. The results derived from the project will allow to define which of the ASOs (anti-FOXP3 or anti-CTLA4) is more effective in the immunomodulation of the vaccine candidate rSsEno+Gel01 anti-Sporothrix.Keywords: Sporotrichosis; Regulatory T cells; CTLA-4; FOXP3; Oligonucleotide; ASO anti-CTLA4; Zoonosis; Self-tolerance; rSsEno; Immunogenicity.