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Evaluation of the amino acid modification, structural characterization and immunogenicity of S. schenckii enolase-derived P1-A and P3-A peptides for a sporotrichosis vaccine

Grant number: 17/13228-0
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): February 06, 2018
Effective date (End): February 05, 2019
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal researcher:Iracilda Zeppone Carlos
Grantee:Deivys Leandro Portuondo Fuentes
Supervisor abroad: Fanny Guzman Quimbayo
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Research place: Pontificia Universidad Católica de Valparaíso (PUCV), Chile  
Associated to the scholarship:15/09340-4 - Identification and synthesis of enolase peptides Sporothrix schenckii as vaccine candidates in sporotrichosis, BP.PD

Abstract

Sporotrichosis is a chronic infection affecting humans and other mammals, caused by species of the genus Sporothrix. The disease has a worldwide distribution, but it is considered an endemic zoonosis in Brazil, mainly in the state of Rio de Janeiro and the metropolitan areas of São Paulo city. The antifungal treatment is very prolonged and often associated with adverse effects, being the prophylactic and/or therapeutic vaccination the most promising alternatives to combat this mycosis. We are currently designing a vaccine candidate based on immunogenic peptides derived from the S. schenckii enolase protein. In the post-doctoral project being developed, the P1-A, P2-A, and P3-A peptides were predicted to bind to TCD4 + and B lymphocytes, however only P2-A showed immunogenicity when formulated with the Pet Gel A adjuvant. This led us to believe that, after chemical synthesis, P1-A and P3-A probably did not acquire a three-dimensional structure similar to that found in the native protein (enolase), thereby limiting its immunogenicity in vivo. In this sense, we propose to increase the immunogenicity of P1-A and P3-A by chemical modification using the ALA-scan technique. The synthesized peptides will be purified, characterized and structurally analyzed by RP-HPLC, mass chromatography, and circular dichroism, respectively. Also, their immunoreactivity will be verified by immunoblotting and their immunogenicity assessed by the titer of antigen-specific IgG antibodies from mice immunized with the peptide/Pet Gel A formulation. These results, together with those previously obtained by the P2-A peptide, will allow us to obtain a more efficient multi-antigenic formulation, capable of inducing immunoreactive antibodies against various regions of enolase.

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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)
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, . (17/13228-0, 17/26774-3, 15/09340-4)

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