Abstract
The dimorphic fungus Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis (PCM). It is believed that approximately 10 million people are infected with the fungus and approximately 2% will eventually develop the disease. Unlike viral and bacterial diseases, fungal diseases are the ones against which there is no commercially available vaccine. Saccharomyces cerevisiae may be a suitable vehicle for immunization against fungal infections, as they require the stimulation of different arms of the immune response. Here we evaluated the efficacy of immunizing mice against PCM by using S. cerevisiae yeast expressing gp43. When challenged by inoculation of P. brasiliensis yeasts, immunized animals showed a protective profile in three different assays. Their lung parenchyma was significantly preserved, exhibiting fewer granulomas with fewer fungal cells than found in non-immunized mice. Fungal burden was reduced in the lung and spleen of immunized mice, and both organs contained higher levels of IL-12 and IFN-γ compared to those of non-vaccinated mice, a finding that suggests the occurrence of Th1 immunity. Taken together, our results indicate that the recombinant yeast vaccine represents a new strategy to confer protection against PCM.
Highlights
The dimorphic fungus Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis (PCM), which is an endemic granulomatous chronic mycosis occurring in Latin America
Western blot analysis of the protein extracts of S. cerevisiae yeast cells expressing tagged gp43 at 4 and 16 hours after induction with galactose showed a band of apparent molecular mass of 66kDa, which corresponds to the predicted size of gp43 in fusion with a HA-His tag plus the protein A ZZ domain (Fig. 1B)
In this study we show that immunization with S. cerevisiae expressing the gp43 recombinant protein prior to challenge with P. brasiliensis protects mice against systemic PCM
Summary
The dimorphic fungus Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis (PCM), which is an endemic granulomatous chronic mycosis occurring in Latin America. Epidemiological data indicate that PCM is found with high incidence in Brazil, Argentina, Colombia, and Venezuela [1,2,3,4]. Infection occurs by inhalation of fungal spores or particles, which transform into the pathogenic yeast form after reaching the pulmonary alveolar epithelium [5]. Yeast can either be eliminated by immune-competent cells or disseminate to other tissues through lymphatic and hematogenous routes, resulting in a spectrum of clinical manifestations, which vary from asymptomatic, benign and localized to severe and disseminated forms (reviewed in [6]). Clinical and experimental evidence indicate that, similar to other.
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