Saccharomyces cerevisiae Expressing Gp43 Protects Mice against Paracoccidioides brasiliensis Infection

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.

Proteomics-Based Characterization of the Humoral Immune Response in Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens

“…In another dimorphic fungus, P . brasiliensis , passive administration of monoclonal antibodies against the immunodominant antigen gp43 or against the recombinant protein before and after intratracheal or intravenous infections reduced fungal burden and decreased pulmonary inflammation in mice [ 75 , 76 ].…”

Immunotherapy for Fungal Infections

“…Protein and glycoprotein from different pathogenic fungi have been studied, and particularly, heat-shock proteins (HSPs) represent an attractive candidate due to their association with both innate and adaptive immunity [226,227]. Immunization with HSPs from Paracoccidioides brasiliensis has been shown to provide some degree of protection against experimental disease [228,229].…”

New insights on the development of fungal vaccines: from immunity to recent challenges

“…In the case of paracoccidioidomycosis (PCM), the disease can appear in two clinical forms, acute and chronic. In each case, the treatment requires long, toxic and intensive antifungal therapy with sulphonamides combined with amphotericin B or azoles ( Muñoz et al 2014 , Assis-Marques et al 2015 ). Despite the long treatment, which can reach up to six months, relapses are frequent ( Assis-Marques et al 2015 ).…”

“…In recent years, several studies in the field of medical mycology have been focused on the development of new vaccines against fungal pathogens. Many pertinent reviews and papers have been published with both new strategies and challenges to the development of antifungal vaccines ( Deepe Jr 1997 , Casadevall et al 2002 , Torosantucci et al 2005 , Cassone 2008 , Edwards Jr 2012 , Iannitti et al 2012 , de Amorim et al 2013 , Muñoz et al 2014 , Assis-Marques et al 2015 , de Almeida et al 2015 ). This increase in interest is due to the rise of dangerous systemic fungal infections, especially related to immunocompromised patients, premature infants, cancer patients and those with invasive treatments for long periods in hospital settings, which are known as high-risk groups ( Spellberg 2011 , Iannitti et al 2012 , Roy & Klein 2012 ).…”