Ssporotrichosis and Chromoblastomycosis: development of vaccines based on immunogenic peptides and determination of immunological markers of protection

• Grant number: 22/11944-9
• Support Opportunities: Research Projects - Thematic Grants
• Duration: August 01, 2024 - July 31, 2029
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Sandro Rogerio de Almeida
• Grantee: Sandro Rogerio de Almeida
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Andrea Regina de Souza Baptista ; Fábio Seiti Yamada Yoshikawa ; Ricardo Jose Giordano ; Shinobu Saijo
• Associated scholarship(s): 24/15557-5 - Analysis of the efficacy of recombinant phage-ZR8 in the vaccination process in mice infected with S. brasiliensis, BP.PD

Abstract

Chromoblastomycosis and sporotrichosis are the two main implantation mycoses that are now recognized as neglected tropical fungal diseases. Its laboratory diagnosis is based mainly on direct microscopy, histopathology and identification of the fungus by culture. Subcutaneous or implantation mycoses, such as sporotrichosis and chromoblastomycosis, result from the inoculation of the pathogenic fungus during trauma, usually cuts by plants or manipulation of the soil. They manifest as a suppurating lesion on the skin or subcutaneous tissue, a product of the spread of the fungus by contiguity or via the lymphatic route. Treatment is difficult, with few therapeutic options and the disease is often recurrent. Sporotrichosis is the most prevalent and widespread implantation mycosis in the world. In recent decades, outbreaks of the disease have been reported in Brazil, mainly by the species S. brasiliensis, which is closely related to zoonotic transmission by cats, in addition to being the species with the highest virulence, atypical clinical manifestations in humans and with high mortality rates for cats. cats. Regarding sporotrichosis, we intend to identify and evaluate a potential recombinant phage vaccine with delivery of the ZR8 peptide, in a murine model, which will later be tested as a possible vaccine for felines, which today are the main vector of the disease. On the other hand, chromoblastomycosis is the second most prevalent implantation mycosis in the world. This disease is caused by melanized fungi (dark pigmentation) mainly Fonsecaea pedrosoi. Chromoblastomycosis is a chronic disease that mostly affects low-income individuals. Its treatment is long, with major side effects and high cost, since there are few antifungals available on the market capable of controlling and eliminating the fungus that causes this disease. Thus, a large number of patients end up interrupting treatment, leading to a high rate of disease recurrence. Therefore, studies aimed at the development of new drugs or techniques to control chromoblastomycosis are of paramount importance. Therefore, we intend to evaluate a potential vaccine using recombinant phage as delivery of the Hp11696 peptide from F. pedrosoi, previously identified in our laboratory, as a potential antigenic target for therapeutic strategies in chromoblastomycosis. We also intend to define, in both models, the importance of the pattern recognition receptors Dectin-1, Dectin-2, as well as the cytokines IFN-g and IL-17, in the protective response of vaccinated animals, using knockout mice. Thus, advances are expected in the formulation of a vaccine strategy against sporotrichosis as well as chromoblastomycosis, in addition to consolidating our knowledge about the immunomodulation of these mycoses of public health importance in our country. (AU)