Paracoccidioidomycosis vaccine

Abstract

Paracoccidioidomycosis is a granulomatous pulmonary infection that is generally controlled by chemotherapy. The efficacy of treatment, however, is limited by the status of the host immune response. The inhibition of a Th-2 immunity or the stimulation of Th-1 cytokines generally increases the efficacy of antifungal drugs. ( 1) This has been achieved by immunization with an internal peptide of the major diagnostic antigen gp43 of Paracoccidioides brasiliensis. Peptide 10 (QTLIAIHTLAIRYAN) elicits an IFN-γ rich Th-1 immune response that protects against experimental intratracheal infection by this fungus. The combination of chemotherapy with P10 immunization showed additive protective effect even after 30 d of infection or in anergic mice, rendering in general, increased production of IL-12 and IFN-γ and reduction of IL-4 and IL-10. Immunotherapy with P10 even in the absence of simultaneous chemotherapy has been effective using various protocols, adjuvants, nanoparticles, P10-primed dendritic cells, and especially a combination of plasmids encoding the P10 minigene and IL-12. Gene therapy, in a long-term infection protocol succeeded in the virtual elimination of the fungus, preserving the lung structure, free from immunopathological side effects.

Keywords: DNA therapy; Gp43; Paracoccidiodes brasiliensis; Peptide P10; Th-1 immune response; adjuvant; vaccine.

Figure 1. Histopathology of lungs from intratracheally infected BALB/c mice. Animals were infected with P. brasiliensis Pb18 for 30 d and treated with pcDNA3-P10 and pORF-mIL-12. (A and C) Untreated infected mice; (B and D) Infected mice immunized with plasmids pP10 and pIL-12 (A and B). Gomori staining showing yeast cells embedded in the lung infiltrate and clearing with plasmid treatment; (C and D) Masson’s trichrome staining showing blue collagen fibers, a granuloma and great number of yeast cells, and the effect of plasmid treatment. Original magnification, 100X.