Identification of Potentially Therapeutic Immunogenic Peptides From Paracoccidioides lutzii Species

Author(s)

Silva, Leandro B. R. ^{[1, 2, 3]} ; Taira, Cleison L. ^[1] ; Cleare, Levi G. ^{[2, 3]} ; Martins, Michele ^[4] ; Junqueira, Magno ^[4] ; Nosanchuk, Joshua D. ^{[2, 3]} ; Taborda, Carlos P. ^{[1, 5]}

Affiliation

^[1] Univ Sao Paulo, Dept Microbiol, Inst Ciencias Biomed, Sao Paulo - Brazil

^[2] Albert Einstein Coll Med, Dept Med, Div Infect Dis, New York, NY - USA

^[3] Albert Einstein Coll Med, Dept Microbiol & Immunol, Div Infect Dis, New York, NY - USA

^[4] Fed Univ Rio Janeiro, Dept Biochem, Prote Unit, Inst Chem, Rio De Janeiro - Brazil

^[5] Univ Sao Paulo, Inst Med Trop Sao Paulo, Fac Med, Dept Dermatol, Lab Micol Med LIM53, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 12, MAY 11 2021.
• Web of Science Citations: 0

Abstract

Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin America caused by the thermodimorphic fungi of the genus Paracoccidioides spp. Paracoccidioides lutzii (PL) is one of the 5 species that constitute the Paracoccidioides genus. PL expresses low amounts of glycoprotein (Gp) 43 (PLGp43) and PLGp43 displays few epitopes in common with the P. brasiliensis (PB) immunodominant antigen PBGp43, which is commonly used for serological diagnosis of PCM. This difference in structure between the glycoproteins markedly reduces the efficiency of serological diagnosis in patients infected with PL. We previously demonstrated that peptide 10 (P10) from the PBGp43 induces protective immune responses in in vitro and in vivo models of PB PCM. Since, P10 has proven to be a promising therapeutic to combat PB, we sought to identify peptides in PL that could similarly be applied for the treatment of PCM. PL yeast cell proteins were isolated from PL: dendritic cell co-cultures and subjected to immunoproteomics. This approach identified 18 PL peptides that demonstrated in silico predictions for immunogenicity. Eight of the most promising peptides were synthesized and applied to lymphocytes obtained from peptide-immunized or PL-infected mice as well as to in vitro cultures with peptides or dendritic cells pulsed the peptides. The peptides LBR5, LBR6 and LBR8 efficiently promoted CD4(+) and CD8(+) T cell proliferation and dendritic cells pulsed with LBR1, LBR3, LBR7 or LBR8 stimulated CD4(+) T cell proliferation. We observed increases of IFN-gamma in the supernatants from primed T cells for the conditions with peptides without or with dendritic cells, although IL-2 levels only increased in response to LBR8. These novel immunogenic peptides derived from PL will be employed to develop new peptide vaccine approaches and the proteins from which they are derived can be used to develop new diagnostic assays for PL and possibly other Paracoccidioides spp. These findings identify and characterize new peptides with a promising therapeutic profile for future against this important neglected systemic mycosis. (AU)

• FAPESP's process: 19/20622-2 - Prospection of new epitopes antigenic from P. lutzii isolate with vaccine potential
• Grantee: Leandro Buffoni Roque da Silva
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 18/25171-6 - Prospection of new epitopes with vaccine potential in the control of experimental infection by Paracoccidioides lutzii
• Grantee: Leandro Buffoni Roque da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/08730-6 - Fungal pathogenicity: environmental effects, immune response and vaccine modulation in the Brazilian endemic mycoses paracoccidioidomycosis and histoplasmosis
• Grantee: Carlos Pelleschi Taborda
• Support Opportunities: Research Projects - Thematic Grants