Navegando por Autor "Teixeira Junior, Antonio Lucio"

Agora exibindo 1 - 7 de 7

Evaluation of a Leishmania hypothetical protein administered as DNA vaccine or recombinant protein against Leishmania infantum infection and its immunogenicity in humans.
(2018) Ribeiro, Patrícia Aparecida Fernandes; Dias, Daniel Silva; Lage, Daniela Pagliara; Costa, Lourena Emanuele; Martins, Vivian Tamietti; Tavares, Grasiele de Sousa Vieira; Mendonça, Débora Vasconcelos Costa; Lima, Mariana Pedrosa; Oliveira, Jamil Silvano de; Steiner, Bethina Trevisol; Ávila, Ricardo Andrez Machado de; Roatt, Bruno Mendes; Chávez Fumagalli, Miguel Angel; Souza, Daniel Menezes; Duarte, Mariana Costa; Teixeira Junior, Antonio Lucio; Coelho, Eduardo Antônio Ferraz
Visceral leishmaniasis (VL) is a fatal disease when acute and untreated. The treatment against this disease is long and presents toxicity and/or high costs. Moreover, parasite resistance has been increasing. Therefore, alternative control measures to avoid the spread of disease should be considered. It is accepted that the development of the T helper (Th)1 immune response, based on the production of pro-inflammatory cytokines, is required for the control of parasites. Although recombinant protein-based vaccines have been tested against VL, they require supplementation with immune adjuvants. In addition, there is a scarcity of studies that comparatively evaluate the efficacy of the immunogens when administered by different delivery systems in mammalian hosts. In the present study, a Leishmania hypothetical protein, LiHyR, was cloned and evaluated by immunization as a plasmid deoxyribonucleic acid (DNA) vaccine or in a recombinant format plus saponin against Leishmania infantum infection. Results showed that both vaccination regimens induced a Th1 cell-based immunity, since high levels of interferon-gamma (IFN-γ), interleukin (IL)-2, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-α) were found, and were associated with the low production of IL-4, IL-10, and anti-parasite immunoglobulin (IgG)1 isotype. In addition, significant reductions in the parasite load were found in the evaluated organs of the DNA LiHyR or rLiHyR/saponin-vaccinated animals. No significant difference was achieved between groups vaccinated with DNA or the recombinant protein. The antigen proved to be also immunogenic in human peripheral blood mononuclear cells (PBMCs) collected from healthy subjects and from untreated and treated VL patients. A higher IgG2 isotype was also found in sera samples of these subjects, thus demonstrating its possible use as a human vaccine. This study demonstrates the protective efficacy of a new Leishmania protein against VL, when it is administered as a DNA vaccine or a recombinant protein plus saponin, and points out its use as a human vaccine against disease.
Evaluation of the protective efficacy of a Leishmania protein associated with distinct adjuvants against visceral leishmaniasis and in vitro immunogenicity in human cells.
(2020) Ribeiro, Patrícia Aparecida Fernandes; Dias, Daniel Silva; Lage, Daniela Pagliara; Mendonça, Débora Vasconcelos Costa; Vale, Danniele Luciana; Ramos, Fernanda Fonseca; Carvalho, Lívia Mendes; Carvalho, Ana Maria Ravena Severino; Steiner, Bethina Trevisol; Roque, Marjorie Coimbra; Silva, João Augusto Oliveira da; Oliveira, Jamil Silvano de; Tavares, Grasiele de Sousa Vieira; Martins, Vivian Tamietti; Chávez Fumagalli, Miguel Angel; Roatt, Bruno Mendes; Moreira, Ricardo Luiz Fontes; Souza, Daniel Menezes; Duarte, Mariana Costa; Oliveira, Mônica Cristina de; Ávila, Ricardo Andrez Machado de; Teixeira Junior, Antonio Lucio; Coelho, Eduardo Antônio Ferraz
The treatment against visceral leishmaniasis (VL) presents problems, mainly related to the toxicity and/or high cost of the drugs. In this context, a prophylactic vaccination is urgently required. In the present study, a Leishmania protein called LiHyE, which was suggested recently as an antigenic marker for canine and human VL, was evaluated regarding its immunogenicity and protective efficacy in BALB/c mice against Leishmania infantum infection. In addition, the protein was used to stimulate peripheral blood mononuclear cells (PBMCs) from VL patients before and after treatment, as well as from healthy subjects. Vaccination results showed that the recombinant (rLiHyE) protein associated with liposome or saponin induced effective protection in the mice, since significant reductions in the parasite load in spleen, liver, draining lymph nodes, and bone marrow were found. The parasitological protection was associated with Th1-type cell response, since high IFN-γ, IL-12, and GM-CSF levels, in addition to low IL-4 and IL-10 production, were found. Liposome induced a better parasitological and immunological protection than did saponin. Experiments using PBMCs showed rLiHyE-stimulated lymphoproliferation in treated patients’ and healthy subjects’ cells, as well as high IFN-γ levels in the cell supernatant. In conclusion, rLiHyE could be considered for future studies as a vaccine candidate against VL..
High-through identification of T cell-specific phage-exposed mimotopes using PBMCs from tegumentary leishmaniasis patients and their use as vaccine candidates against Leishmania amazonensis infection.
(2019) Carvalho, Gerusa Brandão de; Costa, Lourena Emanuele; Lage, Daniela Pagliara; Ramos, Fernanda Fonseca; Santos, Thaís Teodoro de Oliveira; Ribeiro, Patrícia Aparecida Fernandes; Dias, Daniel Silva; Salles, Beatriz Cristina Silveira; Lima, Mariana Pedrosa; Carvalho, Lívia Mendes; Dias, Ana Carolina Silva; Alves, Patrícia Terra; Franklin, Michelle Lucrécio; Silva, Renata A. M.; Duarte, Mariana Costa; Souza, Daniel Menezes; Roatt, Bruno Mendes; Chávez Fumagalli, Miguel Angel; Goulart Filho, Luiz Ricardo; Teixeira Junior, Antonio Lucio; Coelho, Eduardo Antônio Ferraz
In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection
Immunogenicity and protective efficacy of a new Leishmania hypothetical protein applied as a DNA vaccine or in a recombinant form against Leishmania infantum infection.
(2019) Ribeiro, Patrícia Aparecida Fernandes; Dias, Daniel Silva; Lage, Daniela Pagliara; Martins, Vivian Tamietti; Costa, Lourena Emanuele; Santos, Thaís Teodoro de Oliveira; Ramos, Fernanda Fonseca; Tavares, Grasiele de Sousa Vieira; Mendonça, Débora Vasconcelos Costa; Ribeiro, Fernanda Ludolf; Gomes, Dawidson Assis; Rodrigues, Michele Angela; Chávez Fumagalli, Miguel Angel; Silva, Eduardo Sergio da; Galdino, Alexsandro Sobreira; Duarte, Mariana Costa; Roatt, Bruno Mendes; Souza, Daniel Menezes; Teixeira Junior, Antonio Lucio; Coelho, Eduardo Antônio Ferraz
Vaccination is one the most important strategies for the prevention of visceral leishmaniasis (VL). In the current study, a new Leishmania hypothetical protein, LiHyP, which was previously showed as antigenic in an immunoproteomic search in canine VL, was evaluated regarding its immunogenicity and protective efficacy against Leishmania infantum infection. The effects of the immunization using LiHyP were evaluated when administered as a DNA plasmid (DNA LiHyP) or recombinant protein (rLiHyP) associated with saponin. The immunity elicited by both vaccination regimens reduced the parasitism in liver, spleen, bone marrow and draining lymph nodes, being associated with high levels of IFN-γ, IL-12, GM-CSF, and specific IgG2a antibody, besides low production of IL-4, IL-10, and protein and parasite-specific IgG1 antibodies. CD4+ T cells contributed more significantly to IFN-γ production in the rLiHyP/saponin group, while CD8+ T cells were more important in the production of this cytokine in the DNA LiHyP group. In addition, increased IFN-γ secretion, along with low levels of IL-10, were found when PBMCs from treated VL subject and healthy individuals were stimulated with the recombinant protein. In conclusion, when administered either as a DNA plasmid or recombinant protein, LiHyP can direct the immune response towards a Th1 immune profile, protecting animals against L. infantum infection; therefore, it can be seen as a promising immunogen against human VL.
Soluble tumor necrosis factor receptors are associated with severity of kidney dysfunction in pediatric chronic kidney disease.
(2019) Moreira, Janaina Matos; Silva, Albená Nunes da; Vieira, Érica Leandro Marciano; Teixeira Junior, Antonio Lucio; Kummer, Arthur Melo e; Silva, Ana Cristina Simões e
Background In adult chronic kidney disease (CKD) patients, there is a positive association between inflammation and progressive renal dysfunction. Higher levels of soluble receptors of tumor necrosis factor (sTNFR) have been related to worst prognosis of adult CKD patients. Therefore, the present study aimed to evaluate soluble TNF receptors in children and adolescents with CKD and to search for an association with clinical and laboratory features. Methods Demographic, clinical, anthropometric, and laboratory data were evaluated in 34 pediatric patients with CKD and in 34 healthy sex- and age-matched controls. Blood samples were collected in both groups to measure sTNFR by enzyme-linked immunosorbent assay. The modified Schwartz formula was used to estimate glomerular filtration rate (GFR). Results Pediatric patients with CKD had significantly higher plasma concentrations of soluble TNF receptors types 1 and 2 (sTNFR1 and sTNFR2) in comparison to sex- and age-matched healthy controls. Plasma levels of sTNFR1 and sTNFR2 increased progressively as renal function worsened, being inversely and significantly correlated with GFR (r = − 0.853 for sTNFR1 and GFR, r = − 0.729 for sTNFR2 and GFR). Conclusions Children and adolescents with CKD exhibited higher plasma levels of sTNFR1 and sTNFR2 than healthy controls, which increased in relation to renal function deterioration. Plasma levels of sTNFR1 and sTNFR2 emerge as markers of progressive CKD in pediatric patients.
TNFR1 absence protects against memory deficit induced by sepsis possibly through.
(2014) Calsavara, Allan Jefferson Cruz; Soriani, Frederico Marianetti; Vieira, Leda Quercia; Costa, Priscila de Almeida; Rachid, Milene Alvarenga; Teixeira Junior, Antonio Lucio
The involvement of TNF-α type 1 receptor (TNFR1) in memory deficits induced by sepsis was explored by using TNFR1 knockout (KO) mice. We reported that wild type (WT) mice presented memory deficits in the novel object recognition test 10 days after sepsis induced by cecumligation and perforation (CLP). These deficits were not observed in TNFR1 KO mice. The involvement of serum and brain cytokines TNF-α, IL-1β, IL-6, IFN-γ and IL-10 was then investigated. TNFR1 KO mice had higher serum levels of TNF-α and IL-1β, and brain levels of TNF-α than WT mice. After CLP, the brain levels of TNF-α, IL-1β, IL-6 and IFN-γ increased in both WT and KO mice. Our next step was to determine the expression of inflammatory cytokines, BDNF and TrKb in the hippocampus. The absence of TNFR1 inmice subjected to polymicrobial sepsis resulted in higher BDNF expression in the hippocampus. In conclusion, after CLP, memory is preserved in the absence of TNFR1. This finding was associated with increased BDNF expression in the hippocampus.
Vaccination with a CD4+ and CD8+ T-cell epitopes-based recombinant chimeric protein derived from Leishmania infantum proteins confers protective immunity against visceral leishmaniasis.
(2018) Dias, Daniel Silva; Ribeiro, Patrícia Aparecida Fernandes; Martins, Vivian Tamietti; Lage, Daniela Pagliara; Costa, Lourena Emanuele; Chávez Fumagalli, Miguel Angel; Ramos, Fernanda Fonseca; Santos, Thaís Teodoro de Oliveira; Ribeiro, Fernanda Ludolf; Oliveira, Jamil Silvano de; Mendes, Tiago Antônio de Oliveira; Silva, Eduardo Sergio da; Galdino, Alexsandro Sobreira; Duarte, Mariana Costa; Roatt, Bruno Mendes; Souza, Daniel Menezes; Teixeira Junior, Antonio Lucio; Coelho, Eduardo Antônio Ferraz
Vaccination seems to be the best approach to control visceral leishmaniasis (VL). Resistance against infection is based on the development of a Th1 immune response characterized by the production of interferons-γ (IFN-γ), interleukin-12 (IL-12), granulocyte-macrophage-colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α), among others. A number of antigens have been tested as potential targets against the disease; few of them are able to stimulate human immune cells. In the present study, 1 prediction of MHC class I and II molecules-specific epitopes in the amino acid sequences of 3 Leishmania proteins: 1 hypothetical, prohibitin, and small glutamine-rich tetratricopeptide repeat-containing proteins, was performed using bioinformatics tools, and a T-cell epitopes-based recombinant chimeric protein was constructed, synthetized and purified to be evaluated in invitro and in vivo experiments. The purified protein was tested regarding its immunogenicity in peripheral blood mononuclear cells (PBMCs) from healthy subjects and VL patients, as well as to its immunogenicity and protective efficacy in a murine model against Leishmania infantum infection. Results showed a Th1 response based on high IFN-γ and low IL-10 levels derived from in chimera-stimulated PBMCs in both healthy subjects and VL patients. In addition, chimera and/or saponin-immunized mice presented significantly lower parasite burden in distinct evaluated organs, when compared to the controls, besides higher levels of IFN-γ, IL-2, IL-12, and GM-CSF, and an IgG2a isotype-based humoral response. In addition, the CD4+ and CD8+ T-cell subtypes contributed to IFN-γ production in the protected animals. The results showed the immunogenicity in human cells and the protective efficacy against L. infantum in a murine model, and well indicate that this recombinant chimera can be considered as a promising strategy to be used against human disease.