Immunogenicity and preclinical efficacy of a recombinant enolase vaccine candidate against Sporothrix schenckii and Sporothrix brasiliensis

• Grant number: 17/26774-3
• Support Opportunities: Regular Research Grants
• Duration: June 01, 2018 - August 31, 2020
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Iracilda Zeppone Carlos
• Grantee: Iracilda Zeppone Carlos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Sporotrichosis is a mycotic disease of subacute and chronic evolution with cutaneous or subcutaneous nodular lesions, and less frequently disseminated in people with immunological compromise. The causal agent is a dimorphic fungus of the genus Sporothrix which is part of a complex of different species, among them, S. brasiliensis, S. globosa, S. mexicana and S. schenckii sensu stricto of clinical interest, while S. lurei and S. pallida have been identified, but are less related to the occurrence of disease. Zoonotic infections can occur. The cat may be the species with the greatest zoonotic potential, and transmission from cats to people has become an important health problem in Brazil. In recent years, attention has focused on the components of the cell wall of S. schenckii that may be involved in the induction of the immune response and in the adhesion process as virulence mechanism. Previous results from our study group have demonstrated that the serum obtained from mice immunized with an extract of 9 cell wall proteins of S. schenckii ATCC 16345 (Ss16345) formulated with the aluminum hydroxide adjuvant showed reactivity against two proteins, one of 71 kDa and another 47 kDa, the latter being identified as the enolase enzyme present in the strains S. schenckii ATCC 58251, S. schenckii 1099-18 and S. brasiliensis 5110 and predicted as an adhesin by the FungalRV database. Along side these findings, our laboratory has studied for many years the immune response in this fungal infection. Thus we have demonstrated the importance of TLR-4, TLR-2, NLRs (NOD-like) and Dectin-1 receptors in the recognition of S. schenckii. In view of the above, our laboratory has the necessary know how to obtain a vaccine product from the enolase and, furthermore, to deepen the mechanisms of action in the fungus/host interaction. The aim of this project is to evaluate the immunogenicity of the recombinant enolase of S. schenckii (rSsEno) as a potential vaccine antigen against sporotrichosis and to determinate the protective mechanism of the vaccine using a knockout yeast of S. schenckii as a model of infection. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TELLEZ-MARTINEZ, DAMIANA; PORTUONDO, DEIVYS LEANDRO; LOESCH, MARIA LUIZA; BATISTA-DUHARTE, ALEXANDER; CARLOS, IRACILDA ZEPPONE. A Recombinant Enolase-Montanide PetGel A Vaccine Promotes a Protective Th1 Immune Response against a Highly Virulent Sporothrix schenckii by Toluene Exposure. PHARMACEUTICS, v. 11, n. 3, MAR 2019. (17/26774-3)

PORTUONDO, DEIVYS LEANDRO; DORES-SILVA, PAULO ROBERTO; FERREIRA, LUCAS SOUZA; DE OLIVEIRA, CARLOS S.; TELLEZ-MARTINEZ, DAMIANA; MARCOS, CAROLINE MARIA; DE AGUIAR LOESCH, MARIA LUIZA; GUZMAN, FANNY; GAVA, LISANDRA M.; BORGES, JULIO CESAR; et al. Immunization with recombinant enolase of Sporothrix spp. (rSsEno) confers effective protection against sporotrichosis in mice. SCIENTIFIC REPORTS, v. 9, NOV 20 2019. (17/13228-0, 17/26774-3, 15/09340-4)

TELLEZ-MARTINEZ, DAMIANA; BATISTA-DUHARTE, ALEXANDER; PORTUONDO, DEIVYS LEANDRO; CARLOS, IRACILDA ZEPPONE. Prophylactic and therapeutic vaccines against sporotrichosis. Feasibility and prospects. Microbes and Infection, v. 21, n. 10, p. 432-440, DEC 2019. (17/26774-3, 16/04250-0)