Evaluation of the immunogenic properties of Sporothrix spp. thioredoxin reductase protein epitopes for sporotrichosis vaccine purposes

• Grant number: 22/03726-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2022
• Effective date (End): July 31, 2023
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Iracilda Zeppone Carlos
• Grantee: Fernanda Luiza Piccineli
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Sporotrichosis is a fungal disease that affects humans, and other mammals, caused by the pathogenic species of the genus Sporothrix. The disease has a worldwide distribution, endemically affecting Latin America, especially Argentina, Chile, and Brazil, and it is very widespread in the cosmopolitan area. The numbers of clinical cases have been broadly reported in Brazil, where the disease has been an endemic zoonosis for more than two decades, transmitted by cats infected by the species S. brasiliensis. The disease is treated with antifungal drugs, however, this treatment has disadvantages such as cost, long treatment period, and adverse effects, due to these inconveniences it is necessary to search for new prophylactic or therapeutic forms against sporotrichosis. Therefore, the development of a vaccine for cats can significantly contribute to the reduction of zoonotic transmission of the disease. Recent studies have shown that the protein thioredoxin reductase (TR), which is found in the mitochondria and cell walls of Candida albicans, Cryptococcus neoformans, and Paracoccidioides lutzii, has immunogenic properties in BALB/c mice. One of those studies revealed that a recombinant form of this protein could be used safely for vaccination against the diseases caused by these fungi. Based on this background, and considering that the TR protein from Sporothrix spp. has not yet been studied for sporotrichosis vaccine purposes, we carried out an extensive in silico study aimed at identifying peptide regions of this protein for anti-Sporothrix vaccination purposes. From this analysis, three peptides (P1, P2, and P3) containing epitopes of B and T cells, with adhesion properties, without toxic and allergenic properties, are promising antigenic targets for in vivo immunogenicity studies. Thus, the present project aims to evaluate the immunogenic properties of these peptides in BALB/c mice as an essential step in obtaining a safe and protective vaccine against sporotrichosis.(AU)