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Sci Rep
2018 Mar 08;81:4192. doi: 10.1038/s41598-018-22709-8.
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An immunoproteomic approach revealing peptides from Sporothrix brasiliensis that induce a cellular immune response in subcutaneous sporotrichosis.
de Almeida JRF
,
Jannuzzi GP
,
Kaihami GH
,
Breda LCD
,
Ferreira KS
,
de Almeida SR
.
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Sporothrix brasiliensis is the most virulent fungus of the Sporothrix complex and is the main species recovered in the sporotrichosis zoonotic hyperendemic area in Rio de Janeiro. A vaccine against S. brasiliensis could improve the current sporotrichosis situation. Here, we show 3 peptides from S. brasiliensis immunogenic proteins that have a higher likelihood for engaging MHC-class II molecules. We investigated the efficiency of the peptides as vaccines for preventing subcutaneous sporotrichosis. In this study, we observed a decrease in lesion diameters in peptide-immunized mice, showing that the peptides could induce a protective immune response against subcutaneous sporotrichosis. ZR8 peptide is from the GP70 protein, the main antigen of the Sporothrix complex, and was the best potential vaccine candidate by increasing CD4+ T cells and higher levels of IFN-γ, IL-17A and IL-1β characterizing a strong cellular immune response. This immune environment induced a higher number of neutrophils in lesions that are associated with fungus clearance. These results indicated that the ZR8 peptide induces a protective immune response against subcutaneous sporotrichosis and is a vaccine candidate against S. brasiliensis infection.
Figure 1. S. brasiliensis proteome and antigenic proteins. (A) Immunoproteomic approach elaborated. The fungus proteins were fractionated using 7 cm pH 3–10 (left to right) strips in the first dimension and 12% SDS-PAGE gels in the second dimension developed by (B) coomassie staining or (C) silver staining. (D) The spots recognized by western blot with sera from mice infected by S. brasiliensis. (E) The western blot with mAbP6E7.
Figure 2. Selected spots. Selected spots to identification by MALDI–ToF MS/MS.
Figure 3. Cell expansion by peptides ZR3, ZR4 and ZR8 in S. brasiliensis sensitized cells in vitro. (A) The acquired population to exclude cellular debris. In vitro expansion of spleen cells labeled with CFSE with peptides and negative controls. (B–D) DMSO group and (E–J) PBS group. The cytokines levels of (L) IL-17A and (M) IFN-β in the supernatant were measured. Statistical analysis was performed using One-way ANOVA followed by Tukey’s test.
Figure 4. Subcutaneous sporotrichosis by S. brasiliensis. (A) Schematic representation of subcutaneous sporotrichosis model with the peptides vaccine. BALB/c female mice in the 7th, 14th and 21th days were inoculated 20 µg of peptide mixed with Freund’s adjuvant incomplete, in the ratio 1 to 1, in the leg. Mice were inoculated in the subcutaneous tissue 1 × 107 of S. brasiliensis yeast cells. From the 10th to the 35th days post-infection, the average lesion diameter of the (B) DMSO group and of the (C) PBS group was measured. The statistical analysis was performed using Two-way ANOVA followed by Bonferroni post-tests. (D) After 35 days post infection, the lesion fungal burden was evaluated. (E–I) Pictures of lesion from the 15th day post infection.
Figure 5. The protective immune response against sporotrichosis. To determine if the immunization with peptides induce a protective immune response were evaluated the cell profile by the cell number of CD3+/CD4+, CD3+/CD8+ and CD3−/CD19+ respectively in the DMSO group lymph node (A–C) and in the spleen (D–F). The cell profile of CD3+/CD4+, CD3+/CD8+ and CD3−/CD19+ respectively in the PBS group lymph node (H–J) and in the spleen (L–N). In the lesion was evaluated the cell profile GR1+/CD11b+ in the (G) DMSO group and in the (O) PBS group. Statistical analysis was performed using One-way ANOVA followed by Tukey’s test in DMSO group and t-test in PBS group.
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