Therapeutic treatment with scFv-PGLA nanoparticles decreases pulmonary fungal load in a murine model of Paracoccidioidomycosis

Publication date: Available online 23 September 2017
Source:Microbes and Infection
Author(s): Grasielle Pereira Jannuzzi, Nicole de Araújo Souza, Kátia Sanches Françoso, Roney Henrique Pereira, Raquel Possemozer Santos, Gilberto Hideo Kaihami, José Roberto Fogaça de Almeida, Wagner Luiz Batista, André Corrêa Amaral, Andrea Queiroz Maranhão, Sandro Rogério de Almeida, Karen Spadari Ferreira
Paracoccidioidomycosis (PCM) is a systemic mycosis with lymphatic dissemination that is caused by Paracoccidioides species. Treatment of PCM consist 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-γ 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.



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