Evaluation of the immunogenic properties of a multi-epitope protein administered intranasally to BALB/c mice against Sporothrix brasiliensis

• Grant number: 24/07750-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2025
• End date: December 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Iracilda Zeppone Carlos
• Grantee: Beatriz da Cunha Saçaki
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Sporotrichosis is a subacute or chronic mycosis that affects the subcutaneous layer, caused by pathogenic species of the genus Sporothrix. In the national context, this disease is acquired mainly through zoonotic transmission, associated with cats infected by S. brasiliensis. Due to the significant presence of fungal load in severe lesions on the nasal and respiratory mucosa of felines, it is considered that a vaccine administered intranasally could protect these felines from infection by this species more efficiently than a vaccine administered parenterally. In this project we propose to evaluate the immunogenic properties of a vaccine formulation composed of a recombinant protein that contains the immunogenic regions of enolase, Gp70 protein and thioredoxin reductase protein (TR) from Sporothrix spp., a CKS9 peptide (CKSTHPLSC), in addition to two adjuvant sequences, the 50S ribosomal protein L7/L12 of TLR-4 and the universal T epitope PADRE. The recombinant protein, called SpoVac, will be administered to mice intranasally with the mucoadherent adjuvant Montanide Gel 01, which has been shown to improve the immunogenicity of antigens after intranasal immunization in mice and cats. The immunological response will be assessed by the production of antibodies in serum (IgG, IgG1, IgG2a and Ig3) and in saliva (IgA) of vaccinated mice that will be evaluated by the ELISA test. Furthermore, the supernatant of splenocytes from animals stimulated in vitro with the vaccine antigen will be used to quantify the cytokines of the Th1/Th2/Th17 response pattern using the CBA kit. We hope that the formulation can induce the expected immune response to test its protective efficacy in a murine model of intranasal Sporothrix brasiliensis infection.