Investigation of the trained immune response of monocytes and macrophages after exposure to vaccine formulation against systemic mycosis

• Grant number: 20/03532-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: December 30, 2020
• End date: December 29, 2021
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Carlos Pelleschi Taborda
• Grantee: Brenda Kischkel
• Supervisor: Mihai G. Netea
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Radboud University Nijmegen, Netherlands
• Associated to the scholarship: 18/26402-1 - Prospection of new epitopes with vaccine potential in the control of experimental infection by Histoplasma capsulatum, BP.DD

Abstract

Systemic fungal infections are cause by endemic and/or opportunistic fungal pathogens that include species of Aspergillus, Candida, Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Paracoccidioides and Sporothrix. In recent years, the rates of morbidity and mortality from fungal infections have increased significantly due to the increase in the population of immunosuppressed and immunocompromised individuals. The main problems associated with fungal infections include, difficulty in diagnosis, long therapy with side effects and possibility of disease recurrence. In this study, we will work with the concept of trained immunity or innate immune memory for the development of a vaccine. Recently, it was demonstrate that the innate immune system also has memory and can remain on high alert for several months after infection. Thus, responding faster to a second exposure. The discovery that the innate immune system has a memory offers possibilities for training that memory. Ideal approach for immunocompromised individuals who have impaired adaptive immunity. In this proposal, we will investigate of the trained immune response of monocytes and macrophages to an antigen delivery system for vaccination against systemic mycosis. For this, we developed an approach using chitosan and ² - 1,3 - D-glucans (BGs), as a biomaterial platform for the targeted delivery of promiscuous epitopes restricted to HLA class I and II. Our hypothesis is that this may be a strategy capable of inducing a memory-like response in innate cells, thus being able to be used to obtain protective immunity also in people with immune deficiency. (AU)