Therapeutic treatment with scFv-PLGA nanoparticles decreases pulmonary fungal load in a murine model of paracoccidioidomycosis

Author(s):Show less -

Jannuzzi, Grasielle Pereira ^[1] ; Souza, Nicole de Araujo ^[2] ; Francoso, Katia Sanches ^[1] ; Pereira, Roney Henrique ^[1] ; Santos, Raquel Possemozer ^[2] ; Kaihami, Gilberto Hideo ^[3] ; Fogaca de Almeida, Jose Roberto ^[1] ; Batista, Wagner Luiz ^[2] ; Amaral, Andre Correa ^[4] ; Maranhao, Andrea Queiroz ^[5] ; de Almeida, Sandro Rogerio ^[1] ; Ferreira, Karen Spadari ^[2]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Rua Sao Nicolau, 210-4 Andar Diadema, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Quim, Dept Quim, Sao Paulo - Brazil

^[4] Univ Fed Goias, Inst Patol Trop & Saude Publ, Goiania, Go - Brazil

^[5] Univ Brasilia, Dept Biol Celular, Brasilia, DF - Brazil

• Document type: Journal article
• Source: Microbes and Infection; v. 20, n. 1, p. 48-56, JAN 2018.
• Web of Science Citations: 1

Abstract

Paracoccidioidomycosis (PCM) is a systemic mycosis with lymphatic dissemination that is caused by Paracoccidioides species. Treatment of PCM consists of chemotherapeutics such as itraconazole, trimethoprim, sulfamethoxazole or amphotericin B. However, several studies are aiming to develop therapeutic alternatives for the treatment of fungal infection using new molecules as adjuvants. The single-chain variable fragments (scFv) from an antibody that mimics the main fungal component incorporated within poly(lactide-co-glycolic) acid (PLGA) nanoparticles helped treat the fungal disease. After expressing the scFv in Picchia pastoris (P. pastoris), the recombinant molecules were coupled with PLGA, and the BALB/c mice were immunized before or after infection with yeast Paracoccidioides brasiliensis (P. brasiliensis). Our results showed decreased disease progression and decreased fungal burden. Taken together, our results showed an increased of IFN-gamma and IL-12 cytokine production and an increased number of macrophages and dendritic cells in the pulmonary tissue of BALB/c mice treated with a high concentration of our molecule. Our data further confirm that the scFv plays an important role in the treatment of experimental PCM. (C) 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. (AU)

• FAPESP's process: 13/08548-5 - Study of scFv-therapy that mimicking the gp43 antigen from Paracoccidioides brasiliensis combined with nanoparticle in experimental paracoccidioidomycosis
• Grantee: Karen Spadari Ferreira
• Support Opportunities: Regular Research Grants