MARIANA PRADO MARMORATO
Projetos de Pesquisa
Unidades Organizacionais
LIM/60 - Laboratório de Imunologia Clínica e Alergia, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Plasmablast Expansion Following the Tetravalent, Live-Attenuated Dengue Vaccine Butantan-DV in DENV-Naive and DENV-Exposed Individuals in a Brazilian Cohort(2022) SILVEIRA, Cassia G. T.; MAGNANI, Diogo M.; COSTA, Priscilla R.; AVELINO-SILVA, Vivian I.; RICCIARDI, Michael J.; TIMENETSKY, Maria do Carmo S. T.; GOULART, Raphaella; CORREIA, Carolina A.; MARMORATO, Mariana P.; FERRARI, Lilian; NAKAGAWA, Zelinda B.; TOMIYAMA, Claudia; TOMIYAMA, Helena; KALIL, Jorge; PALACIOS, Ricardo; PRECIOSO, Alexander R.; WATKINS, David I.; KALLAS, Esper G.An effective vaccine against the dengue virus (DENV) should induce a balanced, long-lasting antibody (Ab) response against all four viral serotypes. The burst of plasmablasts in the peripheral blood after vaccination may reflect enriched vaccine-specific Ab secreting cells. Here we characterize the acute plasmablast responses from naive and DENV-exposed individuals following immunization with the live attenuated tetravalent (LAT) Butantan DENV vaccine (Butantan-DV). The frequency of circulating plasmablasts was determined by flow cytometric analysis of fresh whole blood specimens collected from 40 participants enrolled in the Phase II Butantan-DV clinical trial (NCT01696422) before and after (days 6, 12, 15 and 22) vaccination. We observed a peak in the number of circulating plasmablast at day 15 after vaccination in both the DENV naive and the DENV-exposed vaccinees. DENV-exposed vaccinees experienced a significantly higher plasmablast expansion. In the DENV-naive vaccinees, plasmablasts persisted for approximately three weeks longer than among DENV-exposed volunteers. Our findings indicate that the Butantan-DV can induce plasmablast responses in both DENV-naive and DENV-exposed individuals and demonstrate the influence of pre-existing DENV immunity on Butantan DV-induced B-cell responses.
- Predictors of mortality in patients with yellow fever: an observational cohort study(2019) KALLAS, Esper G.; ZANELLA, Luiz Gonzaga F. A. B. D'Elia; V, Carlos Henrique Moreira; BUCCHERI, Renata; DINIZ, Gabriela B. F.; CASTINEIRAS, Anna Carla P.; COSTA, Priscilla R.; DIAS, Juliana Z. C.; MARMORATO, Mariana P.; SONG, Alice T. W.; MAESTRI, Alvino; BORGES, Igor C.; JOELSONS, Daniel; CERQUEIRA, Natalia B.; SOUZA, Nathalia C. Santiago e; CLARO, Ingra Morales; SABINO, Ester C.; LEVI, Jose Eduardo; I, Vivian Avelino-Silva; HO, Yeh-LiBackground Yellow fever virus infection results in death in around 30% of symptomatic individuals. The aim of this study was to identify predictors of death measured at hospital admission in a cohort of patients admitted to hospital during the 2018 outbreak of yellow fever in the outskirts of Sao Paulo city, Brazil. Methods In this observational cohort study, we enrolled patients with yellow fever virus from two hospitals in Sao Paolo-the Hospital das Clinicas, University of Sao Paulo and the Infectious Diseases Institute ""Emilio Ribas"". Patients older than 18 years admitted to hospital with fever or myalgia, headache, arthralgia, oedema, rash, or conjunctivitis were consecutively screened for inclusion in the present study. Consenting patients were included if they had travelled to geographical areas in which yellow fever virus cases had been previously confirmed. Yellow fever infection was confirmed by real-time PCR in blood collected at admission or tissues at autopsy. We sequenced the complete genomes of yellow fever virus from infected individuals and evaluated demographic, clinical, and laboratory findings at admission and investigated whether any of these measurements correlated with patient outcome (death). Findings Between Jan 11, 2018, and May 10, 2018, 118 patients with suspected yellow fever were admitted to Hospital das Clinicas, and 113 patients with suspected yellow fever were admitted to Infectious Diseases Institute ""Emilio Ribas"". 95 patients with suspected yellow fever were included in the study, and 136 patients were excluded. Three (3%) of 95 patients with suspected yellow fever who were included in the study were excluded because they received a different diagnosis, and 16 patients with undetectable yellow fever virus RNA were excluded. Therefore, 76 patients with confirmed yellow fever virus infection, based on detectable yellow fever virus RNA in blood (74 patients) or yellow fever virus confirmed only at the autopsy report (two patients), were included in our analysis. 27 (36%) of 76 patients died during the 60 day period after hospital admission. We generated 14 complete yellow fever virus genomes from the first 15 viral load-detectable samples. The genomes belonged to a single monophyletic clade of the South America I genotype, sub-genotype E. Older age, male sex, higher leukocyte and neutrophil counts, higher alanine aminotransferase, aspartate transaminase (AST), bilirubin, and creatinine, prolonged prothrombin time, and higher yellow fever virus RNA plasma viral load were associated with higher mortality. In a multivariate regression model, older age, elevated neutrophil count, increased AST, and higher viral load remained independently associated with death. All 11 (100%) patients with neutrophil counts of 4000 cells per mL or greater and viral loads of 5.1 log(10) copies/mL or greater died (95% CI 72-100), compared with only three (11%) of 27 (95% CI 2-29) among patients with neutrophil counts of less than 4000 cells per mL and viral loads of less than 5.1 log(10) copies/mL. Interpretation We identified clinical and laboratory predictors of mortality at hospital admission that could aid in the care of patients with yellow fever virus. Identification of these prognostic markers in patients could help clinicians prioritise admission to the intensive care unit, as patients often deteriorate rapidly. Moreover, resource allocation could be improved to prioritise key laboratory examinations that might be more useful in determining whether a patient could have a better outcome. Our findings support the important role of the virus in disease pathogenesis, suggesting that an effective antiviral could alter the clinical course for patients with the most severe forms of yellow fever.
- Humoral and cellular immune responses to CoronaVac up to one year after vaccination(2022) COSTA, Priscilla Ramos; CORREIA, Carolina Argondizo; MARMORATO, Mariana Prado; DIAS, Juliana Zanatta de Carvalho; THOMAZELLA, Mateus Vailant; SILVA, Amanda Cabral da; OLIVEIRA, Ana Carolina Soares de; GUSMAO, Arianne Fagotti; FERRARI, Lilian; FREITAS, Angela Carvalho; PATINO, Elizabeth Gonzalez; GRIFONI, Alba; WEISKOPF, Daniela; SETTE, Alessandro; SCHARF, Rami; KALLAS, Esper Georges; SILVEIRA, Cassia Gisele TerrassaniCoronavac is a widely used SARS-CoV-2 inactivated vaccine, but its long-term immune response assessment is still lacking. We evaluated SARS-CoV-2-specific immune responses, including T cell activation markers, antigen-specific cytokine production and antibody response following vaccination in 53 adult and elderly individuals participating in a phase 3 clinical trial. Activated follicular helper T (Tfh), non-Tfh and memory CD4(+) T cells were detected in almost all subjects early after the first vaccine dose. Activated memory CD4(+) T cells were predominantly of central and effector memory T cell phenotypes and were sustained for at least 6 months. We also detected a balanced Th1-, Th2- and Th17/Th22-type cytokine production that was associated with response over time, together with particular cytokine profile linked to poor responses in older vaccinees. SARS-CoV-2-specific IgG levels peaked 14 days after the second dose and were mostly stable over one year. CoronaVac was able to induce a potent and durable antiviral antigen-specific cellular response and the cytokine profiles related to the response over time and impacted by the senescence were defined.
- Latent Mycobacterium tuberculosis Infection Is Associated With a Higher Frequency of Mucosal-Associated Invariant T and Invariant Natural Killer T Cells.(2018) PAQUIN-PROULX, Dominic; COSTA, Priscilla R.; SILVEIRA, Cassia G. Terrassani; MARMORATO, Mariana P.; CERQUEIRA, Natalia B.; SUTTON, Matthew S.; O'CONNOR, Shelby L.; CARVALHO, Karina I.; NIXON, Douglas F.; KALLAS, Esper G.Increasing drug resistance and the lack of an effective vaccine are the main factors contributing to Mycobacterium tuberculosis (Mtb) being a major cause of death globally. Despite intensive research efforts, it is not well understood why some individuals control Mtb infection and some others develop active disease. HIV-1 infection is associated with an increased incidence of active tuberculosis, even in virally suppressed individuals. Mucosal-associated invariant T (MAIT) and invariant natural killer T (iNKT) cells are innate T cells that can recognize Mtb-infected cells. Contradicting results regarding the frequency of MAIT cells in latent Mtb infection have been reported. In this confirmatory study, we investigated the frequency, phenotype, and IFN gamma production of MAIT and iNKT cells in subjects with latent or active Mtb infection. We found that the frequency of both cell types was increased in subjects with latent Mtb infection compared with uninfected individuals or subjects with active infection. We found no change in the expression of HLA-DR, PD-1, and CCR6, as well as the production of IFN. by MAIT and iNKT cells, among subjects with latent Mtb infection or uninfected controls. The proportion of CD4-CD8+ MAIT cells in individuals with latent Mtb infection was, however, increased. HIV-1 infection was associated with a loss of MAIT and iNKT cells, and the residual cells had elevated expression of the exhaustion marker PD-1. Altogether, the results suggest a role for MAIT and iNKT cells in immunity against Mtb and show a deleterious impact of HIV-1 infection on those cells.
conferenceObject SYNDECAN-1 AS A BIOMARKER OF SEVERITY IN ACUTE YELLOW FEVER(2019) SOUSA, Francielle Tramontini Gomes de; MANULI, Erika R.; ZANELLA, Luiz G.; HO, Yeh-Li; NETTO, Lucas Chaves; MARMORATO, Mariana P.; DIAS, Juliana Z.; THOMAZELLA, Mateus V.; CORREIA, Carolina A.; SILVEIRA, Cassia G.; COSTA, Priscilla R.; PEREIRA, Geovana M.; FERREIRA, Midia S.; ROMANO, Camila M.; KALLAS, Esper G.; HARRIS, Eva; SABINO, Ester C.- Viral Kinetics in Sylvatic Yellow Fever Cases(2023) I, Vivian Avelino-Silva; THOMAZELLA, Mateus Vailant; MARMORATO, Mariana Prado; CORREIA, Carolina A.; DIAS, Juliana Z. C.; MAESTRI, Alvino; CERQUEIRA, Natalia B.; V, Carlos H. Moreira; BUCCHERI, Renata; FELIX, Alvina C.; ZANELLA, Luiz G. F. A. B. E.; COSTA, Priscilla R.; KALLAS, Esper G.Yellow fever virus viral load was found to be independently associated with mortality, showing the importance of monitoring viremia and suggesting it as a target to improve disease outcome of an endemic disease with high lethality rate in Brazil. Background Yellow fever is a mosquito-borne zoonotic disease caused by yellow fever virus (YFV). Between 2017 and 2019, more than 504 human cases and 176 deaths were confirmed in the outskirts of Sao Paulo city. Throughout this outbreak, studies suggested a potential association between YFV viremia and mortality. Methods Viral ribonucleic acid was measured using reverse-transcription quantitative polymerase chain reaction in plasma samples collected at up to 5 time points, between 3 and 120 days after symptoms onset. Results Eighty-four patients with confirmed YFV infection were included. Most were males, median age was 42, and 30 (36%) died. Deceased patients were older than survivors (P = .003) and had a higher viremia across all time points (P = .0006). Mean values of viremia had a positive, statistically significant correlation with peak values of neutrophils, indirect bilirubin, aspartate transaminase, international normalized ratio, and creatinine. Finally, a Cox proportional hazards model adjusted for age and laboratory variables showed that viremia is independently associated with death, with a mean 1.84-fold increase (84%) in the hazard of death (P < .001) for each unit increase in mean log(10) viremia. Conclusions Our results raise the importance of monitoring YFV viremia and suggest a potential benefit of antiviral drugs or neutralizing monoclonal antibodies early in the course of this infection to improve disease outcomes.