New advances in the development of a vaccine against paracoccidioidomycosis

Abstract

Paracoccidioidomycosis (PCM) is an endemic Latin American mycosis caused by Paracoccidioides brasiliensis and also by the recently described P. lutzii. The systemic mycosis is the 10th leading cause of death due to infectious diseases in Brazil. As published, 1,853 patients died of PCM in the 1996–2006 decade in this country. The main diagnostic antigen of P.brasiliensis is the 43 kDa glycoprotein gp43, and its 15-mer peptide QTLIAIHTLAIRYAN, known as P10, contains the T-CD4+ epitope that elicits an IFN-γ-mediated Th1 immune response, which effectively treats mice intratracheally infected with PCM. The association of peptide P10 with antifungal drugs rendered an additive protective effect, even in immunosuppressed animals, being the basis of a recommended treatment protocol. Other immunotherapeutic tools include a peptide carrying a B cell epitope as well as protective anti-gp43 monoclonal antibodies. New delivery systems and gene therapy have been studied in prophylactic and therapeutic protocols to improve the efficacy of the recognized antigens aiming at a future vaccine as co-adjuvant therapy in patients with PCM.

Antifungal and antioxidant activity of fatty acid methyl esters from vegetable oils

“…Amphotericin B therapy is the best choice for severe cases of PCM, but toxicity, mainly nephrotoxicity, is related to this drug which will sometimes require discontinuation of this therapy (de Oliveira et al 2015, Ferreira 2009, ShikanaiYasuda 2015. Relapses, a common event in PCM patients, associated with toxicity represent an unresolved problem in the conventional therapeutic approach (Travassos et al 2008, Travassos andTaborda 2012). Due to these facts it is necessary to research new drugs that are safer, more effective and cheaper and with shorter periods of therapy for the treatment of PCM.…”

Heat Shock Proteins in Histoplasma and Paracoccidioides

“…Notably, protective MAbs against surface components of several important fungi, such as Cryptococcus neoformans, Aspergillus fumigatus, C. albicans, and H. capsulatum, have been successfully identified (31,68,69). A panel of MAbs against H. capsulatum Hsp60 proteins that effectively modify the pathogenesis of murine histoplasmosis to the benefit of the host has been generated (70).…”

Paracoccidioidomycosis: level of pulmonary sequelae in high resolution computed tomography images from patients of two endemic regions of Brazil

“…(initially Pb01, a new clade) (3,6). The Paracoccidioides genus exhibits extensive genetic variability, as well as a possible correlation between genotype distribution and geographical isolation, culture adaptation, drug resistance and virulence (6,13,14).…”

“…PCM can be caused by fungi of the Paracoccidioides genus, comprising P. brasiliensis complex, consisting of four cryptic species (S1, PS2, PS3 and PS4) (2,3,12) and P. lutzii. (initially Pb01, a new clade) (3,6).…”