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Prophylactic and Therapeutic Vaccination using Dendritic Cells Primed with Peptide 10 derived from the 43 kDa Glycoprotein of Paracoccidioides brasiliensis.


Vaccination with the peptide-10 (P10), derived from the Paracoccidioides brasiliensis glycoprotein-43 (gp43), induces a Th1 response that protects mice in an intratracheal P. brasiliensis infection model. Combining P10 with Complete Freund's adjuvant (CFA) or other adjuvants further increases the peptide's antifungal effect. Since dendritic cells (DCs) are up to 1000-fold more efficient at activating T cells than CFA, we examined the impact of P10-primed bone-marrow derived DC vaccination in mice. Splenocytes from mice immunized with P10 were stimulated in vitro with P10, or P10-primed DCs. T cell proliferation was significantly increased in the presence of P10 primed DCs compared to the peptide. The protective efficacy of P10-primed DCs was studied in an intratracheal P. brasiliensis model in BALB/c mice. Administration of P10-primed DCs prior to (via subcutaneous vaccination) or weeks after (via either subcutaneous or intravenous injection) P. brasiliensis infection decreased pulmonary damage and significantly reduced fungal burdens. The protective response mediated by the injection of primed-DCs was mainly characterized by an increased production of IFN-g and IL-12 and a reduction in IL-10 and IL-4 compared to infected mice that received saline or unprimed-DCs. Hence, our data demonstrates the potential of P10-primed DCs as a vaccine capable of both the rapid protection against the development of serious paracoccioidomycosis or the treatment of established P. brasiliensis disease. (AU)

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