DNA vaccine encoding peptide P10 against experimental paracoccidioidomycosis induces long-term protection in presence of regulatory T cells

Amorim, Juliana de; Magalhães, Adriana Dias; Muñoz, Julián E.; Rittner, Glauce Mary Gomes; Nosanchuk, Joshua D.; Travassos, Luiz R.; Taborda, Carlos Pelleschi

doi:10.1016/j.micinf.2012.11.007

Cited by 31 publications

(27 citation statements)

References 47 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, since PCM primarily affects rural workers, the disease is associated with significant social and economic factors that mostly affect less affluent populations (Shikanai-Yasuda et al, 2006; de Amorim et al, 2013), so the development of new molecules that could work as a vaccine directed at high-risk populations could be an important step in effective prophylaxis for this disease.…”

Section: Discussionmentioning

confidence: 99%

Peptides Derived from a Phage Display Library Inhibit Adhesion and Protect the Host against Infection by Paracoccidioides brasiliensis and Paracoccidioides lutzii

et al. 2016

View full text Add to dashboard Cite

Paracoccidioides brasiliensis and Paracoccidioides lutzii are dimorphic fungi and are the etiological agents of paracoccidioidomycosis (PCM). Adhesion is one of the most important steps in infections with Paracoccidioides and is responsible for the differences in the virulence of isolates of these fungi. Because of the importance of adhesion to the establishment of an infection, this study focused on the preliminary development of a new therapeutic strategy to inhibit adhesion by Paracoccidioides, thus inhibiting infection and preventing the disease. We used two phage display libraries to select peptides that strongly bind to the Paracoccidioides cell wall to inhibit adhesion to host cells and extracellular matrix (ECM) components (laminin, fibronectin, and type I and type IV collagen). This approach allowed us to identify four peptides that inhibited up to 64% of the adhesion of Paracoccidioides to pneumocytes in vitro and inhibited the adhesion to the ECM components by up to 57%. Encouraged by these results, we evaluated the ability of these peptides to protect Galleria mellonella from Paracoccidioides infection by treating G. mellonella larvae with the different peptides prior to infection with Paracoccidioides and observing larval survival. The results show that all of the peptides tested increased the survival of the larvae infected with P. brasiliensis by up to 64% and by up to 60% in those infected with P. lutzii. These data may open new horizons for therapeutic strategies to prevent PCM, and anti-adhesion therapy could be an important strategy.

show abstract

Section: Discussionmentioning

confidence: 99%

Peptides Derived from a Phage Display Library Inhibit Adhesion and Protect the Host against Infection by Paracoccidioides brasiliensis and Paracoccidioides lutzii

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Another study investigating the role of B-1 cells in pulmonary PCM showed their deleterious effect, which was attributed to the increased migration and activation of Treg cells [107]. In contrast with those previously described deleterious effects of Treg cells, a study employing a repeated immunization with a DNA vaccine encoding the immunoprotective peptide (P10) from gp43, the main diagnostic antigen of P. brasiliensis, conferred a long-term protection to infected mice by inducing increased numbers of memory and regulatory T cells able to control the infectious process and the inflammatory tissue pathology [108].…”

Section: Regulatory T Cells In Murine Pcmmentioning

confidence: 92%

Regulatory T cells in paracoccidioidomycosis

2018

View full text Add to dashboard Cite

This review addresses the role of regulatory T cells (Tregs), which are essential for maintaining peripheral tolerance and controlling pathogen immunity, in the host response against Paracoccidioides brasiliensis, a primary fungal pathogen. A brief introduction on the general features of Treg cells summarizes their main functions, subpopulations, mechanisms of suppression and plasticity. The main aspects of immunity in the diverse forms of the P. brasiliensis infection are presented, as are the few extant studies on the relevance of Treg cells in the control of severity of the human disease. Finally, the influence of Toll-like receptors, Dectin-1, NOD-like receptor P3 (NLRP3), Myeloid differentiation factor-88 (MyD88), as well as the enzyme indoleamine 2,3 dioxygenase (IDO) on the expansion and function of Treg cells in a murine model of pulmonary paracoccidioidomycosis (PCM) is also discussed. It is demonstrated that some of these components are involved in the negative control of Treg cell expansion, whereas others positively trigger the proliferation and activity of these cells. Finally, the studies here summarized highlight the dual role of Treg cells in PCM, which can be protective by controlling excessive immunity and tissue pathology but also deleterious by inhibiting the anti-fungal immunity necessary to control fungal growth and dissemination.

show abstract

“…There are some reports describing the role of antigens inducing immune responses against P. brasiliensis such as soluble antigen, purified antigen, peptide, DNA vaccine and the use of attenuated yeast cells [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Therapeutic Effect of Radioattenuated Yeast Cells in Experimental Paracoccidioidomycosis

Martins¹,

Fern²,

es³

et al. 2014

J Vaccines Vaccin

View full text Add to dashboard Cite

Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis (PCM), the most prevalent deep mycosis in Latin America. The treatment varies according to the chemotherapeutic drug and the disease severity, and the lack of it can results in high frequency of relapse and sequels. Thus, the search for new therapeutic alternatives is necessary. The aim of this study was to evaluate the therapeutic effect of P. brasiliensis yeast cells attenuated by gamma irradiation (LevRad) in Balb/c mice. Mice immunized with LevRad and/or treated with fluconazole presented a significant decrease in the CFU recovery from the lung, liver and spleen in comparison with non-immunized and non-treated infected mice (60 and 120 days after infection). After 120 days from fungal inoculation, no fungi colonies were obtained from the organs of treated and immunized mice. The tissue structure of these organs was largely preserved. At the same time, anti-Mexo specific IgG antibodies levels and TGF-β, IFN-γ, iNOS transcript levels were high and a decrease on the IL-4, IL-10 and TNF-α transcript levels was also verified. An additive protective effect of immunization with LevRad associated to chemotherapy in a PCM experimental model was verified, providing evidence of the therapeutic effect of attenuated yeast for fungal infections.

show abstract

DNA vaccine encoding peptide P10 against experimental paracoccidioidomycosis induces long-term protection in presence of regulatory T cells

Cited by 31 publications

References 47 publications

Peptides Derived from a Phage Display Library Inhibit Adhesion and Protect the Host against Infection by Paracoccidioides brasiliensis and Paracoccidioides lutzii

Peptides Derived from a Phage Display Library Inhibit Adhesion and Protect the Host against Infection by Paracoccidioides brasiliensis and Paracoccidioides lutzii

Regulatory T cells in paracoccidioidomycosis

Evaluation of the Therapeutic Effect of Radioattenuated Yeast Cells in Experimental Paracoccidioidomycosis

Contact Info

Product

Resources

About