EDILBERTO POSTOL

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8
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Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina

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Agora exibindo 1 - 9 de 9
  • article 4 Citação(ões) na Scopus
    StreptInCor, a Group A Streptococcal Adsorbed Vaccine: Evaluation of Repeated Intramuscular Dose Toxicity Testing in Rats
    (2021) SA-ROCHA, Luiz Carlos de; DEMARCHI, Lea Maria Macruz Ferreira; POSTOL, Edilberto; SAMPAIO, Roney Orismar; ALENCAR, Raquel Elaine de; KALIL, Jorge; GUILHERME, Luiza
    Streptococcus pyogenes infections continue to be a worldwide public health problem, causing various diseases in humans, with rheumatic fever and rheumatic heart disease being the most harmful manifestations. Impetigo and post-streptococcal glomerulonephritis are also important sequelae of skin infections. We have developed a candidate vaccine epitope (StreptInCor) that presents promising results in diverse animal models. To assess whether the StreptInCor alum-adsorbed vaccine could induce undesirable effects, a certified independent company conducted a repeated intramuscular dose toxicity evaluation in Wistar rats, a choice model for toxicity studies. We did not observe significant alterations in clinical, hematological, biochemical, anatomical, or histopathological parameters due to vaccine administration, even when the animals received the highest dose. In conclusion, repeated intramuscular doses did not show signs of macroscopic or other significant changes in the clinical or histopathological parameters, indicating that StreptInCor can be considered a safe candidate vaccine.
  • article 37 Citação(ões) na Scopus
    StreptInCor: A Candidate Vaccine Epitope against S. pyogenes Infections Induces Protection in Outbred Mice
    (2013) POSTOL, Edilberto; ALENCAR, Raquel; HIGA, Fabio T.; BARROS, Samar Freschi de; DEMARCHI, Lea M. F.; KALIL, Jorge; GUILHERME, Luiza
    Infection with Streptococcus pyogenes (S. pyogenes) can result in several diseases, particularly in children. S. pyogenes M protein is the major virulence factor, and certain regions of its N-terminus can trigger autoimmune sequelae such as rheumatic fever in susceptible individuals with untreated group A streptococcal pharyngitis. In a previous study, we utilized a large panel of human peripheral blood cells to define the C-terminal protective epitope StreptInCor (medical identity), which does not induce autoimmune reactions. We recently confirmed the results in HLA-transgenic mice. In the present study, we extended the experimental assays to outbred animals (Swiss mice). Herein, we demonstrate high titers of StreptInCor-specific antibodies, as well as appropriate T-cell immune responses. No cross-reaction to cardiac myosin was detected. Additionally, immunized Swiss mice exhibited 87% survival one month after challenge with S. pyogenes. In conclusion, the data presented herein reinforce previous results in humans and animals and further emphasize that StreptInCor could be an effective and safe vaccine for the prevention of S. pyogenes infections.
  • article 41 Citação(ões) na Scopus
    A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses
    (2011) ROSA, Daniela Santoro; RIBEIRO, Susan Pereira; ALMEIDA, Rafael Ribeiro; MAIRENA, Eliane Conti; POSTOL, Edilberto; KALIL, Jorge; CUNHA-NETO, Edecio
    T-cell based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4(+) T cells are important for the generation and maintenance of functional CD8(+) cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18), capable of eliciting broad CD4(+) T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4(+)/CD8(+) T cell responses, and 8/18 vaccine-encoded peptides were recognized. In addition, HIVBr18 immunization was able to induce polyfunctional CD4(+) and CD8(+) T cells that proliferate and produce any two cytokines (IFN gamma/TNF alpha, IFN gamma/IL-2 or TNF alpha/IL-2) simultaneously in response to HIV-1 peptides. For CD4(+) T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFN gamma/TNF alpha/IL-2). The vaccine also generated long-lived central and effector memory CD4(+) T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4(+) T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8(+) T cells and antibody responses-elicited by other HIV immunogens.
  • article 17 Citação(ões) na Scopus
    A Vaccine against Streptococcus pyogenes The Potential to Prevent Rheumatic Fever and Rheumatic Heart Disease
    (2013) GUILHERME, Luiza; FERREIRA, Frederico Moraes; KOEHLER, Karen Francine; POSTOL, Edilberto; KALIL, Jorge
    Streptococcus pyogenes causes severe, invasive infections such as the sequelae associated with acute rheumatic fever, rheumatic heart disease, acute glomerulonephritis, uncomplicated pharyngitis, and pyoderma. Efforts to produce a vaccine against S. pyogenes began several decades ago, and different models have been proposed. We have developed a vaccine candidate peptide, StreptInCor, comprising 55 amino acid residues of the C-terminal portion of the M protein and encompassing both the T- and B-cell protective epitopes. The present article summarizes data from the previous 5 years during which we tested the immunogenicity and safety of StreptInCor in different animal models. We showed that StreptInCor overlapping peptides induced cellular and humoral immune responses of individuals bearing different HLA class II molecules. These results are consistent with peptides that have a universal vaccine epitope. The tridimensional molecular structure of StreptInCor was elucidated by nuclear magnetic resonance spectroscopy, which showed that its structure is composed of two microdomains linked by an 18-residue alpha-helix. Additionally, we comprehensively evaluated the structural stability of the StreptInCor peptide in different physicochemical conditions using circular dichroism. Additional experiments were performed with inbred, outbred, and HLA class II transgenic mice. Analysis of several organs of these mice showed neither deleterious nor autoimmune reactions even after a long period of vaccination, indicating that the StreptInCor candidate peptide could be considered as an immunogenic and safe vaccine.
  • article 12 Citação(ões) na Scopus
    Group A Streptococcus Adsorbed Vaccine: Repeated Intramuscular Dose Toxicity Test in Minipigs
    (2019) POSTOL, Edilberto; SA-ROCHA, Luiz C.; SAMPAIO, Roney O.; DERNARCHI, Lea M. M. F.; ALENCAR, Raquel E.; ABDUCH, Maria C. D.; KALIL, Jorge; GUILHERME, Luiza
    Streptococcus pyogenes infection continues to be a worldwide public health problem causing various diseases in humans and plays an important role in the pathogenesis of rheumatic fever and rheumatic heart disease. We developed a vaccine candidate to prevent S. pyogenes infections, identified as StreptInCor, that presented promising results in mouse models. A certified and independent laboratory conducted two repeated intramuscular dose toxicity tests (28 days, four weekly injections). The first test, composed of four experimental groups treated with 0 (vehicle), 50, 100 or 200 mu g/500 mu L StreptInCor, did not show significant alterations in clinical, hematological, biochemical or anatomopathologica I parameters related to the administration of StreptInCor. In addition to the parameters mentioned above, we evaluated the cardiac function and valves of animals by echocardiography before and after administration of 200 mu g/500 mu L StreptInCor versus placebo. We did not observe any changes related to StreptInCor administration, including changes in cardiac function and valves in animals, after receiving the highest dose of this vaccine candidate. The results obtained in the two repeated intramuscular dose toxicity tests showed that this vaccine formulation did not induce harmful effects to the tissues and organs studied, indicating that the candidate vaccine is well tolerated in minipigs.
  • article 29 Citação(ões) na Scopus
    HLA class II transgenic mice develop a safe and long lasting immune response against StreptInCor, an anti-group A streptococcus vaccine candidate
    (2011) GUERINO, Milton T.; POSTOL, Edilberto; DEMARCHI, Lea M. F.; MARTINS, Carlo O.; MUNDEL, Luiz R.; KALIL, Jorge; GUILHERME, Luiza
    Streptococcus pyogenes infections remain a health problem in several countries because of post-streptococcal sequelae, such as rheumatic fever and rheumatic heart disease. We developed a vaccine epitope (StreptInCor) composed of 55 amino acid residues of the C-terminal portion of the M protein that encompasses both T and B cell protective epitopes. Recently, by using human blood samples, we showed that the StreptInCor epitope is able to bind to different HLA class 11 molecules and that it could be considered a universal vaccine epitope. In the present work, we evaluated the immune response of HLA class II transgenic mice against aluminum hydroxide-absorbed StreptInCor. After a period of one year, several organs were analyzed histologically to verify the safety of the candidate vaccine epitope. Our results showed that StreptInCor is able to induce robust and safe and long lasting immune response without deleterious reactions in several organs. In conclusion, the results presented here indicate that StreptInCor could be considered a safe vaccine against severe streptococcus-induced diseases.
  • article 9 Citação(ões) na Scopus
    Rheumatic Heart Disease: Pathogenesis and Vaccine
    (2018) GUILHERME, L.; BARROS, S. Freschi de; KOHLER, K. F.; SANTOS, S. R.; FERREIRA, F. Morais; SILVA, W. R.; ALENCAR, R.; POSTOL, E.; KALIL, J.
    Rheumatic fever (RF) and rheumatic heart disease (RHD) follow untreated S. pyogenes throat infections in children who present susceptible genes that favor the development of autoimmune reactions. In this review, we focus on the genes that confer susceptibility and on the autoimmune reactions that occur due to molecular mimicry between human-tissue proteins and streptococcal M protein. Polyarthritis is the initial manifestation, which can evolve to carditis and severe valve damage; these culminate in rheumatic heart disease (RHD) or Sydenham's chorea, which affects the central nervous system. A perspective on vaccine development to prevent the disease is also discussed.
  • article 29 Citação(ões) na Scopus
    Analysis of the coverage capacity of the StreptInCor candidate vaccine against Streptococcus pyogenes
    (2014) AMICIS, Karine M. De; BARROS, Samar Freschi de; ALENCAR, Raquel E.; POSTOL, Edilberto; MARTINS, Carlo de Oliveira; ARCURI, Helen Andrade; GOULART, Cibelly; KALIL, Jorge; GUILHERME, Luiza
    Streptococcus pyogenes is responsible for infections as pharyngitis, sepsis, necrotizing fasciitis and streptococcal toxic shock syndrome. The M protein is the major bacterial antigen and consists of both polymorphic N-terminal portion and a conserved region. In the present study, we analyzed the in vitro ability of StreptInCor a C-terminal candidate vaccine against S. pyogenes to induce antibodies to neutralize/opsonize the most common S. pyogenes strains in Sao Paulo by examining the recognition by sera from StreptInCor immunized mice. We also evaluated the presence of cross-reactive antibodies against human heart valve tissue. Anti-StreptInCor antibodies were able to neutralize/opsonize at least 5 strains, showing that immunization with StreptInCor is effective against several S. pyogenes strains and can prevent infection and subsequent sequelae without causing autoimmune reactions.
  • article 12 Citação(ões) na Scopus
    Streptococcus pyogenes strains in Sao Paulo, Brazil: molecular characterization as a basis for StreptInCor coverage capacity analysis
    (2015) BARROS, Samar Freschi de; AMICIS, Karine Marafigo De; ALENCAR, Raquel; SMEESTERS, Pierre Robert; TRUNKEL, Ariel; POSTOL, Edilberto; ALMEIDA JUNIOR, Joao Nobrega; ROSSI, Flavia; PIGNATARI, Antonio Carlos Campos; KALIL, Jorge; GUILHERME, Luiza
    Background: Several human diseases are caused by Streptococcus pyogenes, ranging from common infections to autoimmunity. Characterization of the most prevalent strains worldwide is a useful tool for evaluating the coverage capacity of vaccines under development. In this study, a collection of S. pyogenes strains from Sao Paulo, Brazil, was analyzed to describe the diversity of strains and assess the vaccine coverage capacity of StreptInCor. Methods: Molecular epidemiology of S. pyogenes strains was performed by emm-genotyping the 229 isolates from different clinical sites, and PCR was used for superantigen profile analysis. The emm-pattern and tissue tropism for these M types were also predicted and compared based on the emm-cluster classification. Results: The strains were fit into 12 different emm-clusters, revealing a diverse phylogenetic origin and, consequently, different mechanisms of infection and escape of the host immune system. Forty-eight emm-types were distinguished in 229 samples, and the 10 most frequently observed types accounted for 69 % of all isolates, indicating a diverse profile of circulating strains comparable to other countries under development. A similar proportion of E and A-C emm-patterns were observed, whereas pattern D was less frequent, indicating that the strains of this collection primarily had a tissue tropism for the throat. In silico analysis of the coverage capacity of StreptInCor, an M protein-conserved regionally based vaccine candidate developed by our group, had a range of 94.5 % to 59.7 %, with a mean of 71.0 % identity between the vaccine antigen and the predicted amino acid sequence of the emm-types included here. Conclusions: This is the first report of S. pyogenes strain characterization in Sao Paulo, one of the largest cities in the world; thus, the strain panel described here is a representative sample for vaccine coverage capacity analysis. Our results enabled evaluation of StreptInCor candidate vaccine coverage capacity against diverse M-types, indicating that the vaccine candidate likely would induce protection against the diverse strains worldwide.