LUIZA GUILHERME GUGLIELMI
Projetos de Pesquisa
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 - Líder
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
8 resultados
Resultados de Busca
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- 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, LuizaStreptococcus 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.
- Anti-Group A Streptococcal Vaccine Epitope STRUCTURE, STABILITY, AND ITS ABILITY TO INTERACT WITH HLA CLASS II MOLECULES(2011) GUILHERME, Luiza; ALBA, Martha P.; FERREIRA, Frederico Moraes; OSHIRO, Sandra Emiko; HIGA, Fabio; PATARROYO, Manuel E.; KALIL, JorgeStreptococcus pyogenes infections remain a health problem in several countries due to poststreptococcal sequelae. We developed a vaccine epitope (StreptInCor) composed of 55 amino acids residues of the C-terminal portion of the M protein that encompasses both T and B cell protective epitopes. The nuclear magnetic resonance (NMR) structure of the StreptInCor peptide showed that the structure was composed of two microdomains linked by an 18-residue alpha-helix. A chemical stability study of the StreptInCor folding/unfolding process using far-UV circular dichroism showed that the structure was chemically stable with respect to pH and the concentration of urea. The T cell epitope is located in the first microdomain and encompasses 11 out of the 18 alpha-helix residues, whereas the B cell epitope is in the second microdomain and showed no alpha-helical structure. The prediction of StreptInCor epitope binding to different HLA class II molecules was evaluated based on an analysis of the 55 residues and the theoretical possibilities for the processed peptides to fit into the P1, P4, P6, and P9 pockets in the groove of several HLA class II molecules. We observed 7 potential sites along the amino acid sequence of StreptInCor that were capable of recognizing HLA class II molecules (DRB1*, DRB3*, DRB4*, and DRB5*). StreptInCoroverlapping peptides induced cellular and humoral immune responses of individuals bearing different HLA class II molecules and could be considered as a universal vaccine epitope.
- 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, LuizaInfection 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.
- 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, LuizaStreptococcus 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.
- 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, LuizaStreptococcus 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.
- Incidental Diagnosis of Rheumatic Myocarditis during Cardiac Surgery-Impact on Late Prognosis(2023) VIEIRA, Paulo Pinto Alves Campos; PEREIRA, Rodrigo Furtado; BRANCO, Carlos Eduardo Barros; ROSA, Vitor Emer Egypto; VIEIRA, Marcelo Luiz Campos; DEMARCHI, Lea Maria Macruz Ferreira; SILVA, Livia Santos; GUILHERME, Luiza; TARASOUTCHI, Flavio; SAMPAIO, Roney OrismarRheumatic fever (RF) and rheumatic heart disease (RHD) are still highly prevalent, particularly in low- and middle-income countries. RHD is a neglected and underdiagnosed disease for which no specific laboratory diagnostic test is completely reliable. This is a retrospective observational study, which included 118 patients with RHD who underwent cardiac surgery from 1985 to 2018. The aim of this investigation was to evaluate the clinical, epidemiological, echocardiographic and pathological characteristics in two cohorts of RHD patients: one cohort with Aschoff bodies present in their pathological results and the other without such histopathological characteristics. No conventional clinical and laboratory tests for RHD myocarditis were able to identify active carditis during the preoperative phase of valve repair or replacement. Patients who had Aschoff bodies in their pathological results were younger (median age of 13 years (11-24 years) vs. 27 years (17-37 years), p = 0.001) and had higher rate of late mortality (22.9% vs. 5.4%, p = 0.043). In conclusion, the presence of Aschoff bodies in pathological findings may predict increased long-term mortality, emphasizing the importance of comprehensive pathology analysis for suspected myocarditis during heart surgery.
- Rheumatic Heart Disease and Myxomatous Degeneration: Differences and Similarities of Valve Damage Resulting from Autoimmune Reactions and Matrix Disorganization(2017) MARTINS, Carlo de Oliveira; DEMARCHI, Lea; FERREIRA, Frederico Moraes; POMERANTZEFF, Pablo Maria Alberto; BRANDAO, Carlos; SAMPAIO, Roney Orismar; SPINA, Guilherme Sobreira; KALIL, Jorge; CUNHA-NETO, Edecio; GUILHERME, LuizaAutoimmune inflammatory reactions leading to rheumatic fever (RF) and rheumatic heart disease (RHD) result from untreated Streptococcus pyogenes throat infections in individuals who exhibit genetic susceptibility. Immune effector mechanisms have been described that lead to heart tissue damage culminating in mitral and aortic valve dysfunctions. In myxomatous valve degeneration (MXD), the mitral valve is also damaged due to non-inflammatory mechanisms. Both diseases are characterized by structural valve disarray and a previous proteomic analysis of them has disclosed a distinct profile of matrix/structural proteins differentially expressed. Given their relevance in organizing valve tissue, we quantitatively evaluated the expression of vimentin, collagen VI, lumican, and vitronectin as well as performed immunohistochemical analysis of their distribution in valve tissue lesions of patients in both diseases. We identified abundant expression of two isoforms of vimentin (45 kDa, 42 kDa) with reduced expression of the full-size protein (54 kDa) in RHD valves. We also found increased vitronectin expression, reduced collagen VI expression and similar lumican expression between RHD and MXD valves. Immunohistochemical analysis indicated disrupted patterns of these proteins in myxomatous degeneration valves and disorganized distribution in rheumatic heart disease valves that correlated with clinical manifestations such as valve regurgitation or stenosis. Confocal microscopy analysis revealed a diverse pattern of distribution of collagen VI and lumican into RHD and MXD valves. Altogether, these results demonstrated distinct patterns of altered valve expression and tissue distribution/ organization of structural/matrix proteins that play important pathophysiological roles in both valve diseases.
- 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, LuizaStreptococcus 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.