Vaccine Development to Systemic Mycoses by Thermally Dimorphic Fungi

Abstract

Purpose of Review Pathogenic thermal-dimorphic fungi are endemic in certain regions and can cause from subclinical respiratory infections to systemic mycoses. These pathogens are associated with high rates of mortality and high morbidity, infecting thousands of people each year. In addition, the toxicity and high costs of treatment of systemic mycoses are great public health concerns. In the present review, we address recent studies that refer to the development of vaccines against systemic mycoses by thermally dimorphic fungi. Recent Findings Members of the genus Paracoccidioides, Histoplasma, Coccidioides, and Blastomyces are thermal-dimorphic fungi, and the difficulty in obtaining new and selective antifungal therapies led to the increase of research involving development of new options of immune therapy. Immunotherapeutic strategies and new vaccines have been focused on protecting populations at risk and assisting in antifungal treatment, reducing the time of therapy and toxicity. Peptides, purified antigens, DNA therapy, dendritic cells, in addition to the use of attenuated yeast cells and monoclonal antibodies, have been explored as potential vaccines. Summary In recent years, despite advances in the search for new antifungal therapies with a focus on the development of prophylactic and/or therapeutic vaccines, few prototypes of successful treatment have emerged from clinical trials. It is clear, however, that all information from these studies, concerning the pathogen-host relationship and the understanding of the immune response to these microorganisms, are indispensable for the development of new treatment options aiming at reducing the morbidity and mortality of populations at risk for these infections.

Therapeutic Vaccination with Cationic Liposomes Formulated with Dioctadecyldimethylammonium and Trehalose Dibehenate (CAF01) and Peptide P10 Is Protective in Mice Infected with Paracoccidioides brasiliensis

“…[10]. Therapeutic or prophylactic vaccines are important promising tools for the prevention or treatment of patients with fungal infections [11]. The peptide P10 (QTLIAIHTLAIRYAN) has been highlighted as a vaccine candidate against PCM [12].…”

“…Although the orthology of a glycoprotein of 43kDa in P. lutzii (Plgp43) has only 80% of identity with gp43, both are structurally related to fungal exo-glucanases [16]. Previous studies have shown that the administration of P10 vaccine with different adjuvants can reduce the fungal burden and elicit a mixed cellular immune response characterized by a predominant Th 1 response with production of IFN-γ, TNF-α and IL-12 in murine infection models [11,17].…”