Immunization with recombinant enolase of Sporothrix spp. (rSsEno) confers effective protection against sporotrichosis in mice

Abstract

In recent years, research has focused on the immunoreactive components of the Sporothrix schenckii cell wall that can be relevant targets for preventive and therapeutic vaccines against sporotrichosis, an emergent worldwide mycosis. In a previous study, we identified a 47-kDa enolase as an immunodominant antigen in mice vaccinated with an adjuvanted mixture of S. schenckii cell wall proteins. Here, we sought to assess the protective potential of a Sporothrix spp. recombinant enolase (rSsEno) formulated with or without the adjuvant Montanide Pet-GelA (PGA) against the S. brasiliensis infection in mice. Mice that were immunized with rSsEno plus PGA showed increased antibody titters against rSsEno and increased median survival time when challenged with S. brasiliensis as compared with mice that had not been immunized or that were immunized with rSsEno alone. Immunization with rSsEno plus PGA induced a predominantly T-helper 1 cytokine pattern after in vitro stimulation of splenic cells with rSsEno: elevated levels of IFN-γ and IL-2, as well as of other cytokines involved in host defense against sporotrichosis, such as TNF-alpha, IL-6, and IL-4. Furthermore, we show for the first time the presence of enolase in the cell wall of both S. schenckii and S. brasiliensis. As a whole, our results suggest that enolase could be used as a potential antigenic target for vaccinal purposes against sporotrichosis.

Guideline for the management of feline sporotrichosis caused by Sporothrix brasiliensis and literature revision

“…A vaccine based on peptides of a GP70 antigen showed protection against S. globosa [139] and S. brasiliensis [140]. Another study demonstrated the protective capacity of a vaccine based on recombinant enolase (rSsEno) and Montanide™ Pet Gel A (PGA) as an adjuvant against S. schenckii [141]. However, despite all efforts, there is no immunoprophylaxis or immunotherapy yet available against Sporothrix spp.…”

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

“…With these initial results, an experimental study to evaluate the effect of the administration of anti-Foxp3 ASO on the immunogenicity of an experimental vaccine against Sporothrix schenckii previously developed in our laboratory [ 27 , 28 ] was carried out. We used the same experimental design previously described but including the anti-Foxp3 ASO within the formulation to determine its effect on the specific immune response.…”

“…The experimental vaccine used in this study was designed for the prevention of sporotrichosis, a worldwide emergent subcutaneous mycosis caused by pathogenic species of the genus S. schenckii . The recombinant-Enolase vaccine tested in this study was recently developed by our group and was suggested to be protective against experimental infection in mice [ 27 , 29 ]. Administration of anti-Foxp3 ASO as part of the vaccine formulation induced a considerable upregulation of the Th1-type cytokines IFN-γ and IL-12 in immunized mice.…”

“…We studied the kinetics of Foxp3 ASO access into CD4+ T cells. The functional effects of the ASO on Treg depletion, cytotoxicity, and its ability to enhance the immunogenicity of an antifungal adjuvanted vaccine against sporotrichosis [ 27 ] were also evaluated.…”

Profissionais De Saúde E Participação Popular: Políticas Públicas E Tomadas De Decisões Em Saúde

“…As técnicas biotecnológicas também contribuem para obtenção de estrutura biológica nativa de alvos terapêuticos. Em 2019, três importantes estudos revelam proteínas recombinantes como alvos relevantes para desenvolvimento de vacinas preventivas e terapêuticas contra espécies causadoras de esporotricose, criptococose e candidemia (HESTER et al, 2019;PORTUONDO et al, 2019;SINGH et al, 2019).…”