Navegando por Autor "Galdino, Alexsandro Sobreira"
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Item Canine visceral leishmaniasis biomarkers and their employment in vaccines.(2019) Giunchetti, Rodolfo Cordeiro; Silveira, Patricia; Resende, Lucilene Aparecida; Leite, Jaqueline Costa; Melo Júnior, Otoni Alves de Oliveira; Alves, Marina Luiza Rodrigues; Costa, Laís Moreira; Lair, Daniel Ferreira; Chaves, Vinícius Rossi; Soares, Ingrid dos Santos; Mendonça, Ludmila Zanandreis de; Lanna, Mariana Ferreira; Ribeiro, Helen Silva; Gonçalves, Ana Alice Maia; Santos, Thaiza Aline Pereira; Roatt, Bruno Mendes; Soares, Rodrigo Dian de Oliveira Aguiar; Souza, Juliana Vitoriano de; Moreira, Nádia das Dores; Siqueira, Fernando Augusto Mathias; Cardoso, Jamille Mirelle de Oliveira; Vital, Wendel Coura; Galdino, Alexsandro Sobreira; Viana, Kelvinson Fernandes; Martins Filho, Olindo Assis; Lemos, Denise da Silveira; Dutra, Walderez Ornelas; Reis, Alexandre BarbosaThe natural history of canine visceral leishmaniasis (CVL) has been well described, particularly with respect to the parasite load in different tissues and immunopathological changes according to the progression of clinical forms. The biomarkers evaluated in these studies provide support for the improvement of the tools used in developing vaccines against CVL. Thus, we describe the major studies using the dog model that supplies the rationale for including different biomarkers (tissue parasitism, histopathology, hematological changes, leucocytes immunophenotyping, cytokines patterns, and in vitro co-culture systems using purified T-cells subsets and macrophages infected with L. infantum) for immunogenicity and protection evaluations in phases I and II applied to pre-clinical and clinical vaccine trials against CVL. The search for biomarkers related to resistance or susceptibility has revealed a mixed cytokine profile with a prominent proinflammatory immune response as relevant for Leishmania replication at low levels as observed in asymptomatic dogs (highlighted by high levels of IFN-γ and TNF-α and decreased levels in IL-4, TGF-β and IL-10). Furthermore, increased levels in CD4+ and CD8+ T-cell subsets, presenting intracytoplasmic proinflammatory cytokine balance, have been associated with a resistance profile against CVL. In contrast, a polyclonal B-cell expansion towards plasma cell differentiation contributes to high antibody production, which is the hallmark of symptomatic dogs associated with high susceptibility in CVL. Finally, the different studies used to analyze biomarkers have been incorporated into vaccine immunogenicity and protection evaluations. Those biomarkers identified as resistance or susceptibility markers in CVL have been used to evaluate the vaccine performance against L. infantum in a kennel trial conducted before the field trial in an area known to be endemic for visceral leishmaniasis. This rationale has been a guiding force in the testing and selection of the best vaccine candidates against CVL and provides a way for the veterinary industry to register commercial immunobiological products.Item Empreendedorismo universitário.(2019) Freitas, Alan Ferreira de; Galdino, Alexsandro Sobreira; Cunha, Bernardo Gonçalves da; Toledo, Cristiane Bittencourt Barroso; Gonçalves, Daniel Bonoto; Carvalho, Dárlinton Barbosa Feres; Lemos, Denise da Silveira; Pereira, Eduardo Bento; Soares, Eduardo Emrich; Colares, Heloísa Carneiro; Magalhães, Juliana Teixeira de; Nogueira, Lais Moreira; Lunardi, Laura Martuscelli; Felicori, Liza; Oliveira, Lucilene Aparecida Resende; Speziali, Marcelo Gomes; Paz, Mariana Campos da; Mohallem, Nelcy Della Santina; Silveria, Patricia; Granjeiro, Paulo Afonso; Mariano, Reysla; Oliveira, Rita de Cássia; Giunchetti, Rodolfo Cordeiro; Bianchi, Rodrigo Fernando; Lomeo, Rosangela da Silva; Oliveira, Sabrina Feliciano; Paiva, Sofia Larissa da Costa; Monteiro, Soraia A.; Silva, Tuânia Natacha LopesItem 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 FerrazVaccination 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.Item Immunotherapy using immunogenic mimotopes selected by phage display plus amphotericin B inducing a therapeutic response in mice infected with Leishmania amazonenses.(2023) Soyer, Tauane Gonçalves; Ramos, Fernanda Fonseca; Pereira, Isabela Amorim Gonçalves; Lage, Daniela Pagliara; Bandeira, Raquel Soares; Jesus, Marcelo Moreira de; Costa, Guilherme de Paula; Machado, Amanda Sanchez; Freitas, Camila Simões de; Vale, Danniele Luciana; Martins, Vivian Tamietti; Galdino, Alexsandro Sobreira; Chávez Fumagalli, Miguel Angel; Souza, Daniel Menezes; Duarte, Mariana Costa; Roatt, Bruno Mendes; Coelho, Eduardo Antônio Ferraz; Tavares, Grasiele de Sousa VieiraLeishmania amazonensis can cause cutaneous and visceral clinical manifestations of leish- maniasis in infected hosts. Once the treatment against disease is toxic, presents high cost, and/or there is the emergence of parasite-resistant strains, alternative means through which to control the disease must be developed. In this context, immunotherapeutics combining known drugs with immunogens could be applied to control infections and allow hosts to recover from the disease. In this study, immunotherapeutics protocols associating mimotopes selected by phage display and amphotericin B (AmpB) were evaluated in L. amazonensis-infected mice. Immunogens, A4 and A8 phages, were administered alone or associated with AmpB. Other animals received saline, AmpB, a wild-type phage (WTP), or WTP/AmpB as controls. Evaluations performed one and thirty days after the application of immunotherapeutics showed that the A4/AmpB and A8/AmpB combinations induced the most polarized Th1-type immune responses, which reflected in significant reductions in the lesion’s average diameter and in the parasite load in the infected tissue and distinct organs of the animals. In addition, the combination also reduced the drug toxicity, as compared to values found using it alone. In this context, preliminary data presented here suggest the potential to associate A4 and A8 phages with AmpB to be applied in future studies for treatment against leishmaniasis.Item Nanoformulations with Leishmania braziliensis antigens triggered controlled parasite burden in vaccinated golden hamster (Mesocricetus auratus) against visceral leishmaniasis.(2022) Ottino, Jennifer; Leite, Jaqueline Costa; Melo Júnior, Otoni Alves de Oliveira; Cabrera González, Marco Antonio; Carvalho, Tatiane Furtado de; Garcia, Giani Martins; Batista, Maurício Azevedo; Silveira, Patrícia; Cardoso, Mariana Santos; Bueno, Lilian Lacerda; Fujiwara, Ricardo Toshio; Santos, Renato Lima; Paes, Paulo Ricardo de Oliveira; Lemos, Denise da Silveira; Martins Filho, Olindo Assis; Galdino, Alexsandro Sobreira; Chávez Fumagalli, Miguel Angel; Dutra, Walderez Ornelas; Mosqueira, Vanessa Carla Furtado; Giunchetti, Rodolfo CordeiroLeishmaniasis is a widespread vector-borne disease in Brazil, with Leishmania (Leishmania) infantum as the primary etiological agent of visceral leishmaniasis (VL). Dogs are considered the main reservoir of this parasite, whose treatment in Brazil is restricted to the use of veterinary medicines, which do not promote a parasitological cure. Therefore, efficient vaccine development is the best approach to Canine Visceral Leishmaniasis (CVL) control. With this in mind, this study used hamsters (Mesocricetus auratus) as an experimental model in an anti-Leishmania preclinical vaccine trial to evaluate the safety, antigenicity, humoral response, and effects on tissue parasite load. Two novel formulations of nanoparticles made from poly(D, L-lactic) acid (PLA) polymer loading Leishmania braziliensis crude antigen (LB) exhibiting two different particle sizes were utilized: LBPSmG (570 nm) and LBPSmP (388 nm). The results showed that the nanoparticles were safe and harmless to hamsters and were antigenic with the induction in LBSap, LBPSmG, and LBPSmG groups of total anti-Leishmania IgG antibodies 30 days after challenge, which persists 200 days in LBSap and LBPSmP. At the same time, a less pronounced hepatosplenomegaly in LBSap, LBPSmG, and LBPSmP was found when compared to control groups, as well as a less pronounced inflammatory infiltrate and granuloma formation in the spleen. Furthermore, significant reductions of 84%, 81%, and 90% were observed in spleen parasite burden accessed by qPCR in the LBSap, LBPSmG, and LBPSmP groups, respectively. In this way, LBSap, LBPSmG, and LBPSmP formulations showed better results in vaccinated and L. infantum-challenged animals in further reducing parasitic load in the spleen and attenuating lesions in liver and splenic tissues. This results in safe, harmless nanoformulation vaccines with significant immunogenic and infection control potential. In addition, animals vaccinated with LBPSmP had an overall reduction in parasite burden in the spleen, indicating that a smaller nanoparticle could be more efficient in targeting antigen-presenting cells.Item Provocações empreendedoras 3 : business no mestrado e doutorado.(Editora Paco Editorial, 2020) Silva, André Luís; Galdino, Alexsandro Sobreira; Paz, Mariana Campos daItem Recombinant endonuclease III protein from Leishmania infantum associated with Th1-type adjuvants is immunogenic and induces protection against visceral leishmaniasis.(2023) Lage, Daniela Pagliara; Machado, Amanda Sanchez; Freitas, Camila Simões de; Vale, Danniele Luciana; Linhares, Flávia Prata; Cardoso, Jamille Mirelle de Oliveira; Silva, João Augusto Oliveira da; Ramos, Fernanda Fonseca; Pereira, Isabela Amorim Gonçalves; Ribeiro, Fernanda Ludolf; Tavares, Grasiele de Sousa Vieira; Bandeira, Raquel Soares; Oliveira, Jamil Silvano de; Souza, Daniel Menezes; Duarte, Mariana Costa; Galdino, Alexsandro Sobreira; Christodoulides, Myron; Chávez Fumagalli, Miguel Angel; Roatt, Bruno Mendes; Martins, Vívian Tamietti; Coelho, Eduardo Antônio FerrazVaccination against visceral leishmaniasis (VL) should be considered as a safe and effective measure to disease control; however, few vaccines are available against canine VL and there is no an approved human vaccine. In this context, in the present study, we evaluated the endonuclease III (ENDO) protein, which was recently showed to be antigenic for human disease, as a vaccine candidate against Leishmania infantum infection. The recombinant protein (rENDO) was administered in BALB/c mice alone or associated with saponin (rENDO/Sap) or micelles (rENDO/Mic) as adjuvants. Controls received saline, saponin or empty micelles. Results showed that both rENDO/Sap and rENDO/Mic compositions induced higher levels of IFN-γ, IL-12, TNF-α, and GM-CSF cytokines, besides nitrite and IgG2a isotype antibodies, before and after challenge infection, which were related to both CD4+ and CD8+ T cell subtypes. The immunological results contributed to significant reductions in the parasite load found in the spleens, livers, bone marrows and draining lymph nodes of the vaccinated animals. In general, mice immunized with rENDO/Mic presented a slightly higher Th1-type cellular and humoral immune response, as compared to those receiving rENDO/Sap. In addition, saponin caused a slight to moderate inflammatory edema in their vaccinated footpads, which was not observed when micelles were used with rENDO. In addition, a preliminary analysis showed that the recombinant protein was immunogenic to human cells cultures, since PBMCs from treated VL patients and healthy subjects showed higher lymphoproliferation and IFN-γ production in the culture supernatants. In conclusion, data suggest that rENDO could be considered as a candidate to be evaluated in future studies as vaccine to protect against VL.Item 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 FerrazVaccination 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.Item Vaccination with formulation of nanoparticles loaded with Leishmania amazonensis antigens confers protection against experimental visceral leishmaniasis in hamster.(2023) Cabrera González, Marco Antonio; Gonçalves, Ana Alice Maia; Ottino, Jennifer; Leite, Jaqueline Costa; Resende, Lucilene Aparecida; Melo Júnior, Otoni Alves de Oliveira; Silveira, Patricia; Cardoso, Mariana Santos; Fujiwara, Ricardo Toshio; Bueno, Lilian Lacerda; Santos, Renato Lima; Carvalho, Tatiane Furtado de; Garcia, Giani Martins; Paes, Paulo Ricardo de Oliveira; Galdino, Alexsandro Sobreira; Chávez Fumagalli, Miguel Angel; Melo, Marilia Martins; Lemos, Denise da Silveira; Martins Filho, Olindo Assis; Dutra, Walderez Ornelas; Mosqueira, Vanessa Carla Furtado; Giunchetti, Rodolfo CordeiroVisceral leishmaniasis (VL) is a fatal disease caused by the protozoa Leishmania infantum for which dogs are the main reservoirs. A vaccine against canine visceral leishmaniasis (CVL) could be an important tool in the control of human and CVL by reducing the infection pressure of L. infantum. Despite the CVL vaccine available on the market, the Brazilian Ministry of Health did not implement the use of it in their control programs. In this sense, there is an urgent need to develop more efficient vaccines. In this study, the association between two polymeric nanoformulations, (poly (D, L-lactic) acid (PLA) polymer) loading Leishmania amazonensis antigens, was evaluated as a potential immunobiological agent against VL using golden hamsters as an experimental model. The results indicated that no significant adverse reactions were observed in animals vaccinated with LAPSmP. LAPSmP presented similar levels of total anti-Leishmania IgG as compared to LAPSmG. The LAPSmP and LAPSmG groups showed an intense reduction in liver and spleen parasitic load by qPCR. The LAPSmP and LAPSmG vaccines showed exceptional results, indicating that they may be promising candidates as a VL vaccine.