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

Jannuzzi, Grasielle Pereira; Souza, N. de; Françoso, Kátia Sanches; Pereira, Roney Henrique; Santos, Raquel Possemozer; Kaihami, Gilberto Hideo; Almeida, José Roberto Fogaça de; Batista, Wagner L.; Amaral, André Corrêa; Maranhão, Andréa Queiroz; Almeida, Sandro Rogério de; Ferreira, Karen Spadari

doi:10.1016/j.micinf.2017.09.003

Cited by 15 publications

(11 citation statements)

References 34 publications

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“…When expressed in dendritic cells that were administered to mice, it triggered an enhanced T cell response, elevated levels of anti-gp43 antibodies, and a dramatic reduction in the number of viable fungi. In a subsequent study, the same group demonstrated that the protective effect could be further enhanced if the scFv molecules were incorporated into poly(lactide-co-glycolic) acid nanoparticles [85].…”

Section: Protective Antibodies Against Dimorphic Fungimentioning

confidence: 96%

Monoclonal Antibodies as Tools to Combat Fungal Infections

Ulrich

Ebel

2020

JoF

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Antibodies represent an important element in the adaptive immune response and a major tool to eliminate microbial pathogens. For many bacterial and viral infections, efficient vaccines exist, but not for fungal pathogens. For a long time, antibodies have been assumed to be of minor importance for a successful clearance of fungal infections; however this perception has been challenged by a large number of studies over the last three decades. In this review, we focus on the potential therapeutic and prophylactic use of monoclonal antibodies. Since systemic mycoses normally occur in severely immunocompromised patients, a passive immunization using monoclonal antibodies is a promising approach to directly attack the fungal pathogen and/or to activate and strengthen the residual antifungal immune response in these patients.

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Section: Protective Antibodies Against Dimorphic Fungimentioning

confidence: 96%

Monoclonal Antibodies as Tools to Combat Fungal Infections

Ulrich

Ebel

2020

JoF

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“…The authors suggest that the treatment modulated the humoral immune response with production of IgG2a and IgG1. Despite the positive data demonstrated, the results obtained in the prophylactic treatment need to be further developed [53].…”

Section: Paracoccidioidomycosismentioning

confidence: 99%

Vaccine Development to Systemic Mycoses by Thermally Dimorphic Fungi

et al. 2019

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Purpose of Review Pathogenic thermal-dimorphic fungi are endemic in certain regions and can cause from subclinical respiratory infections to systemic mycoses. These pathogens are associated with high rates of mortality and high morbidity, infecting thousands of people each year. In addition, the toxicity and high costs of treatment of systemic mycoses are great public health concerns. In the present review, we address recent studies that refer to the development of vaccines against systemic mycoses by thermally dimorphic fungi. Recent Findings Members of the genus Paracoccidioides, Histoplasma, Coccidioides, and Blastomyces are thermal-dimorphic fungi, and the difficulty in obtaining new and selective antifungal therapies led to the increase of research involving development of new options of immune therapy. Immunotherapeutic strategies and new vaccines have been focused on protecting populations at risk and assisting in antifungal treatment, reducing the time of therapy and toxicity. Peptides, purified antigens, DNA therapy, dendritic cells, in addition to the use of attenuated yeast cells and monoclonal antibodies, have been explored as potential vaccines. Summary In recent years, despite advances in the search for new antifungal therapies with a focus on the development of prophylactic and/or therapeutic vaccines, few prototypes of successful treatment have emerged from clinical trials. It is clear, however, that all information from these studies, concerning the pathogen-host relationship and the understanding of the immune response to these microorganisms, are indispensable for the development of new treatment options aiming at reducing the morbidity and mortality of populations at risk for these infections.

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“…Variable single-chain fragments (scFv) obtained from the monoclonal antibody (mAb) 7.B12 that mimics gp43, the main P. brasiliensis antigen was incorporated into PLGA. After scFv-PLGA treatment of infected mice, a reduction in fungal load and increased production of IFN-γ and IL-12 cytokines was observed, as well as an abundance of macrophages and dendritic cells was seen in the lung tissue (Jannuzzi et al, 2018). Ribeiro et al (2013) used liposomes and PLGA to deliver plasmids containing the genetic information necessary for the expression of Mycobacterium leprae heat shock proteins (DNAhsp65).…”

Section: Aspergillosismentioning

confidence: 99%

“…Although promising, vaccines that have been studied against PCM have shown a rapid degradation of the immunogen (Travassos and Taborda, 2012 ). The most efficient way to protect the immunogenic molecule, reduce its concentration and reduce the number of doses was achieved by complexing it into NPs, as shown by Amaral et al ( 2010 ), Jannuzzi et al ( 2018 ), and Ribeiro et al ( 2013 ). For example, the immunomodulatory peptide P10 trapped in PLGA NPs was effective in treating chronic murine PCM after 90 days of treatment with 5 or 10 50 μL −1 , and the P10-PLGA NPs induced a robust, protective Th1 immune response (Amaral et al, 2010 ).…”

Section: Current Scenario Of Nanotechnology In the Treatment And Vaccmentioning

confidence: 99%

Therapies and Vaccines Based on Nanoparticles for the Treatment of Systemic Fungal Infections

Kischkel

Rossi

Santos

et al. 2020

Front. Cell. Infect. Microbiol.

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Treatment modalities for systemic mycoses are still limited. Currently, the main antifungal therapeutics include polyenes, azoles, and echinocandins. However, even in the setting of appropriate administration of antifungals, mortality rates remain unacceptably high. Moreover, antifungal therapy is expensive, treatment periods can range from weeks to years, and toxicity is also a serious concern. In recent years, the increased number of immunocompromised individuals has contributed to the high global incidence of systemic fungal infections. Given the high morbidity and mortality rates, the complexity of treatment strategies, drug toxicity, and the worldwide burden of disease, there is a need for new and efficient therapeutic means to combat invasive mycoses. One promising avenue that is actively being pursued is nanotechnology, to develop new antifungal therapies and efficient vaccines, since it allows for a targeted delivery of drugs and antigens, which can reduce toxicity and treatment costs. The goal of this review is to discuss studies using nanoparticles to develop new therapeutic options, including vaccination methods, to combat systemic mycoses caused by Candida sp., Cryptococcus sp., Paracoccidioides sp., Histoplasma sp., Coccidioides sp., and Aspergillus sp., in addition to providing important information on the use of different types of nanoparticles, nanocarriers and their corresponding mechanisms of action.

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

Cited by 15 publications

References 34 publications

Monoclonal Antibodies as Tools to Combat Fungal Infections

Monoclonal Antibodies as Tools to Combat Fungal Infections

Vaccine Development to Systemic Mycoses by Thermally Dimorphic Fungi

Therapies and Vaccines Based on Nanoparticles for the Treatment of Systemic Fungal Infections

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