CASSIA GISELE TERRASSANI SILVEIRA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
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- 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.
- Global Assessment of Dengue Virus-Specific CD4(+) T Cell Responses in Dengue-Endemic Areas(2017) GRIFONI, Alba; ANGELO, Michael A.; LOPEZ, Benjamin; O'ROURKE, Patrick H.; SIDNEY, John; CERPAS, Cristhiam; BALMASEDA, Angel; SILVEIRA, Cassia G. T.; MAESTRI, Alvino; COSTA, Priscilla R.; DURBIN, Anna P.; DIEHL, Sean A.; PHILLIPS, Elizabeth; MALLAL, Simon; SILVA, Aruna D. De; NCHINDA, Godwin; NKENFOU, Celine; COLLINS, Matthew H.; SILVA, Aravinda M. de; LIM, Mei Qiu; MACARY, Paul A.; TATULLO, Filippo; SOLOMON, Tom; SATCHIDANANDAM, Vijaya; DESAI, Anita; RAVI, Vasanthapram; COLOMA, Josefina; TURTLE, Lance; RIVINO, Laura; KALLAS, Esper G.; PETERS, Bjoern; HARRIS, Eva; SETTE, Alessandro; WEISKOPF, DanielaBackground: Dengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV). To enable global assessment of CD4(+) T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4(+) T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua. Methods: HLA class II epitopes in the population of Managua were identified by an in vitro IFN gamma ELISPOT assay. CD4(+) T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen-presenting cells, followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a ""megapool"" (MP) consisting of 180 peptides specifically designed to achieve balanced HLA and DENV serotype coverage. The DENV CD4MP(180) was validated by intracellular cytokine staining assays. Results: We detected responses directed against a total of 431 epitopes, representing all 4 DENV serotypes, restricted by 15 different HLA-DRB1 alleles. The responses were associated with a similar pattern of protein immunodominance, overall higher magnitude of responses, as compared to what was observed previously in the Sri Lanka region. Based on these epitope mapping studies, we designed a DENV CD4 MP180 with higher and more consistent coverage, which allowed the detection of CD4(+) T cell DENV responses ex vivo in various cohorts of DENV exposed donors worldwide, including donors from Nicaragua, Brazil, Singapore, Sri Lanka, and U.S. domestic flavivirus-naive subjects immunized with Tetravalent Dengue Live-Attenuated Vaccine (TV005). This broad reactivity reflects that the 21 HLA-DRB1 alleles analyzed in this and previous studies account for more than 80% of alleles present with a phenotypic frequency >= 5% worldwide, corresponding to 92% phenotypic coverage of the general population (i.e., 92% of individuals express at least one of these alleles). Conclusion: The DENV CD4 MP180 can be utilized to measure ex vivo responses to DENV irrespective of geographical location.
- 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.