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PLoS One
2015 Jan 01;106:e0129401. doi: 10.1371/journal.pone.0129401.
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scFv from Antibody That Mimics gp43 Modulates the Cellular and Humoral Immune Responses during Experimental Paracoccidioidomycosis.
Jannuzzi GP
,
Tavares AH
,
Kaihami GH
,
de Almeida JR
,
de Almeida SR
,
Ferreira KS
.
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Paracoccidioidomycosis (PCM), caused by Paracoccidioides species is a prevalent systemic and progressive mycosis that occurs in Latin America. It is caused by Paracoccidioides species. Immunization with dendritic cells transfected with a plasmid encoding the scFv (pMAC/PS-scFv) that mimics the main antigen of P. brasiliensis (gp43) confers protection in experimental PCM. DCs link innate and adaptive immunity by recognizing invading pathogens and selecting the type of effector T cell to mediate the immune response. Here, we showed that DC-pMAC/PS-scFv induces the activation of CD4+ and CD8+ T cells. Moreover, our results demonstrated that BALB/c mice infected with P. brasiliensis and treated with DC-pMAC/PS-scFv showed the induction of specific IgG production against gp43 and IFN-γ, IL-12 and IL-4 cytokines. Analysis of regional lymph nodes revealed increases in the expression of clec7a, myd88, tlr2, gata3 and tbx21, which are involved in the immune response. Taken together, our results indicate that the scFv modulates the humoral and cellular immune responses and presents epitopes to CD4+ and CD8+ T cells.
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Fig 2. Gene expression.After intramuscular immunization in BALB/c mice (seven/group) with PBS, pMAC/PS or pMAC/PS-scFv, total RNA from lymph nodes was extracted and the gene expression were analyzed by PCR array. (A) clec7a; (B) tlr2; (C) tlr4; (D) myd88; (E) gata3 and (F) tbx 21. *p<0.05 and **p<0.001. Results are representative of three independent experiments.
Fig 4. DCs molecule expression.DCs were transfected with pMAC/PS-scFv. After 48 hours the total DCs were stained with anti-MHCII/CD11c, anti-CD86, anti-CD40 and anti-CD80. The data were analyzed by flow cytometer. Results are representative of three independent experiments.
Fig 5. Phenotype of lung cells.BALB/c mice (seven/group) were infected with P. brasiliensis yeast (1x106). After that, the animals received twice treatments with PBS (50μL), DC (1x106), DC-pMAC/PS (1x106 cells plus 20ng/mL DNA) and DC-pMAC/PS-scFv (1x106 cells plus 20ng/mL DNA). After seven days from the last treatment, the lung cells were stained with anti-CD3e/CD4 (A), anti-CD3e/CD8 (B) and anti-CD40/CCR7 (C). As control of the infection, BALB/c mice received only PBS (50μL) by intratracheal pathway. The data was analyzed by flow cytometer. Flow cytometry graphs: one representative experiment is shown.
Ahmad,
scFv antibody: principles and clinical application.
2012, Pubmed
Ahmad,
scFv antibody: principles and clinical application.
2012,
Pubmed
Beninati,
Therapy of mucosal candidiasis by expression of an anti-idiotype in human commensal bacteria.
2000,
Pubmed
Beninati,
Protective immunization against group B meningococci using anti-idiotypic mimics of the capsular polysaccharide.
2004,
Pubmed
Bennett,
Help for cytotoxic-T-cell responses is mediated by CD40 signalling.
1998,
Pubmed
Bocca,
Paracoccidioidomycosis: eco-epidemiology, taxonomy and clinical and therapeutic issues.
2013,
Pubmed
Bradford,
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
1976,
Pubmed
Brown,
Innate antifungal immunity: the key role of phagocytes.
2011,
Pubmed
Buss,
Monoclonal antibody therapeutics: history and future.
2012,
Pubmed
Cano,
Pulmonary paracoccidioidomycosis in resistant and susceptible mice: relationship among progression of infection, bronchoalveolar cell activation, cellular immune response, and specific isotype patterns.
1995,
Pubmed
Chiarella,
The relative importance of CD4+ and CD8+T cells in immunity to pulmonary paracoccidioidomycosis.
2007,
Pubmed
Coffman,
Vaccine adjuvants: putting innate immunity to work.
2010,
Pubmed
Ferreira,
Interaction between Paracoccidioides brasiliensis and pulmonary dendritic cells induces interleukin-10 production and toll-like receptor-2 expression: possible mechanisms of susceptibility.
2007,
Pubmed
Ferreira,
Dendritic cells transfected with scFv from Mab 7.B12 mimicking original antigen gp43 induces protection against experimental Paracoccidioidomycosis.
2011,
Pubmed
Fortes,
Immunology of paracoccidioidomycosis.
2011,
Pubmed
Herzenberg,
Interpreting flow cytometry data: a guide for the perplexed.
2006,
Pubmed
Inaba,
Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.
1992,
Pubmed
Jeong,
Recombinant antibodies: engineering and production in yeast and bacterial hosts.
2011,
Pubmed
Magliani,
Therapeutic potential of antiidiotypic single chain antibodies with yeast killer toxin activity.
1997,
Pubmed
Nisonoff,
Implications of the presence of an internal image of the antigen in anti-idiotypic antibodies: possible application to vaccine production.
1981,
Pubmed
Parker,
Design, production, and characterization of a single-chain variable fragment (ScFv) derived from the prostate specific membrane antigen (PSMA) monoclonal antibody J591.
2013,
Pubmed
Puccia,
43-kilodalton glycoprotein from Paracoccidioides brasiliensis: immunochemical reactions with sera from patients with paracoccidioidomycosis, histoplasmosis, or Jorge Lobo's disease.
1991,
Pubmed
Puccia,
Exocellular components of Paracoccidioides brasiliensis: identification of a specific antigen.
1986,
Pubmed
Ribeiro,
Nanobiotechnological approaches to delivery of DNA vaccine against fungal infection.
2013,
Pubmed
Ribeiro,
DNAhsp65 vaccination induces protection in mice against Paracoccidioides brasiliensis infection.
2009,
Pubmed
Rittner,
Therapeutic DNA vaccine encoding peptide P10 against experimental paracoccidioidomycosis.
2012,
Pubmed
Schoenberger,
T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions.
1998,
Pubmed
Souza,
B and T cell responses elicited by monoclonal anti-idiotypic antibody (Ab2beta) mimicking gp43 from Paracoccidioides brasiliensis.
2004,
Pubmed
Souza,
Evidence of idiotypic modulation in the immune response to gp43, the major antigenic component of Paracoccidioides brasiliensis in both mice and humans.
1998,
Pubmed
Sánchez-Sánchez,
The multiple personalities of the chemokine receptor CCR7 in dendritic cells.
2006,
Pubmed
Travassos,
Paracoccidioidomycosis vaccine.
2012,
Pubmed
Villadangos,
Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo.
2007,
Pubmed
Weck,
hDectin-1 is involved in uptake and cross-presentation of cellular antigens.
2008,
Pubmed
do Nascimento Martins,
Immunization with radioattenuated yeast cells of Paracoccidioides brasiliensis induces a long lasting protection in BALB/c mice.
2007,
Pubmed
