PRISCILLA RAMOS COSTA
Projetos de Pesquisa
Unidades Organizacionais
LIM/60 - Laboratório de Imunologia Clínica e Alergia, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- 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.
- Prior Dengue Virus Exposure Shapes T Cell Immunity to Zika Virus in Humans(2017) GRIFONI, Alba; PHAM, John; SIDNEY, John; O'ROURKE, Patrick H.; PAUL, Sinu; PETERS, Bjoern; MARTINI, Sheridan R.; SILVA, Aruna D. de; RICCIARDI, Michael J.; MAGNANI, Diogo M.; SILVEIRA, Cassia G. T.; MAESTRI, Alvino; COSTA, Priscilla R.; DE-OLIVEIRA-PINTO, Luzia Maria; AZEREDO, Elzinandes Leal de; DAMASCO, Paulo Vieira; PHILLIPS, Elizabeth; MALLAL, Simon; SILVA, Aravinda M. de; COLLINS, Matthew; DURBIN, Anna; DIEHL, Sean A.; CERPAS, Cristhiam; BALMASEDA, Angel; KUAN, Guillermina; COLOMA, Josefina; HARRIS, Eva; CROWE JR., James E.; STONE, Mars; NORRIS, Phillip J.; BUSCH, Michael; VIVANCO-CID, Hector; COX, Josephine; GRAHAM, Barney S.; LEDGERWOOD, Julie E.; TURTLE, Lance; SOLOMON, Tom; KALLAS, Esper G.; WATKINS, David I.; WEISKOPF, Daniela; SETTE, AlessandroWhile progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here, we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether preexisting dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with tetravalent dengue attenuated vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors but declines in DENV-preexposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells from DENV-preexposed donors selectively upregulated granzyme B and PD1, unlike DENV-naive donors. Finally, we discovered that ZIKV structural proteins (E, prM, and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins. IMPORTANCE The issue of potential ZIKV and DENV cross-reactivity and how preexisting DENV T cell immunity modulates Zika T cell responses is of great relevance, as the two viruses often cocirculate and Zika virus has been spreading in geographical regions where DENV is endemic or hyperendemic. Our data show that memory T cell responses elicited by prior infection with DENV recognize ZIKV-derived peptides and that DENV exposure prior to ZIKV infection influences the timing, magnitude, and quality of the T cell response. Additionally, we show that ZIKV-specific responses target different proteins than DENV-specific responses, pointing toward important implications for vaccine design against this global threat.
- 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.
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.- Safety and immunogenicity of the tetravalent, live-attenuated dengue vaccine Butantan-DV in adults in Brazil: a two-step, double-blind, randomised placebo-controlled phase 2 trial(2020) KALLAS, Esper G.; PRECIOSO, Alexander Roberto; PALACIOS, Ricardo; THOME, Beatriz; BRAGA, Patricia Emilia; VANNI, Tazio; CAMPOS, Lucia M. A.; FERRARI, Lilian; MONDINI, Gabriella; SALOMAO, Maria da Graca; SILVA, Anderson da; ESPINOLA, Heloisa M.; SANTOS, Joane do Prado; SANTOS, Cecilia L. S.; TIMENETSKY, Maria do Carmo S. T.; MIRAGLIA, Joao Luiz; GALLINA, Neuza M. F.; WEISKOPF, Daniela; SETTE, Alessandro; GOULART, Raphaella; SALLES, Rafael Tavares; MAESTRI, Alvino; SALLUM, Adriana Maluf Elias; FARHAT, Sylvia Costa Lima; SAKITA, Neusa K.; FERREIRA, Juliana C. O. A.; SILVEIRA, Cassia G. T.; COSTA, Priscilla R.; RAW, Isaias; WHITEHEAD, Stephen S.; DURBIN, Anna P.; KALIL, JorgeBackground The Butantan Institute has manufactured a lyophilised tetravalent live-attenuated dengue vaccine Butantan-DV, which is analogous to the US National Institutes of Health (NIH) TV003 admixture. We aimed to assess the safety and immunogenicity of Butantan-DV. Methods We did a two-step, double-blind, randomised placebo-controlled phase 2 trial at two clinical sites in Sao Paulo, Brazil. We recruited healthy volunteers aged 18-59 years; pregnant women, individuals with a history of neurological, heart, lung, liver or kidney disease, diabetes, cancer, or autoimmune diseases, and individuals with HIV or hepatitis C were excluded. Step A was designed as a small bridge-study between Butantan-DV and TV003 in DENV-naive participants. In step A, we planned to randomly assign 50 dengue virus (DENV)-naive individuals to receive two doses of Butantan-DV, TV003, or placebo, given 6 months apart. In step B, we planned to randomly assign 250 participants (DENV-naive and DENV-exposed) to receive one dose of Butantan-DV or placebo. Participants were randomly assigned, by computer-generated block randomisation (block sizes of five); participants in step A were randomly assigned (2:2:1) to receive Butantan-DV, TV003, or placebo and participants in step B were randomly assigned (4:1) to receive Butantan-DV or placebo. Participants and study staff were unaware of treatment allocation. The primary safety outcome was the frequency of solicited and unsolicited local and systemic adverse reactions within 21 days of the first vaccination, analysed by intention to treat. The primary immunogenicity outcome was seroconversion rates of the DENV-1-4 serotypes measured 91 days after the first vaccination, analysed in the per-protocol population, which included all participants in step A, and all participants included in step B who completed all study visits with serology sample collection. This trial is registered with ClinicalTrials. gov, NCT01696422. Findings Between Nov 5, 2013, and Sept 21, 2015, 300 individuals were enrolled and randomly assigned: 155 (52%) DENV-naive participants and 145 (48%) DENV-exposed participants. Of the 155 DENV-naive participants, 97 (63%) received Butantan-DV, 17 (11%) received TV003, and 41 (27%) received placebo. Of the 145 DENV-exposed participants, 113 (78%) received Butantan-DV, three (2%) received TV003, and 29 (20%) received placebo. Butantan-DV and TV003 were both immunogenic, well-tolerated, and no serious adverse reactions were observed. In step A, rash was the most frequent adverse event (16 [845] of 19 participants in the Butantan-DV group and 13 [76%] of 17 participants in the TV003 group). Viraemia was similar between the Butantan-DV and TV003 groups. Of the 85 DENV-naive participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis and thus were included in the per-protocol analysis population, 74 (87%) achieved seroconversion to DENV-1, 78 (92%) to DENV-2, 65 (76%) to DENV-3, and 76 (89%) to DENV-4. Of the 101 DENV-exposed participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis, 82 (81%) achieved seroconversion to DENV-1, 79 (78%) to DENV-2, 83 (82%) to DENV-3, and 78 (77%) to DENV-4. Interpretation Butantan-DV and TV003 were safe and induced robust, balanced neutralising antibody responses against the four DENV serotypes. Efficacy evaluation of the Butantan-DV vaccine is ongoing.
- Potent Plasmablast-Derived Antibodies Elicited by the National Institutes of Health Dengue Vaccine(2017) MAGNANI, Diogo M.; SILVEIRA, Cassia G. T.; RICCIARDI, Michael J.; GONZALEZ-NIETO, Lucas; PEDRENO-LOPEZ, Nuria; BAILEY, Varian K.; GUTMAN, Martin J.; MAXWELL, Helen S.; DOMINGUES, Aline; COSTA, Priscilla R.; FERRARI, Lilian; GOULART, Raphaella; MARTINS, Mauricio A.; MARTINEZ-NAVIO, Jose M.; FUCHS, Sebastian P.; KALIL, Jorge; TIMENETSKY, Maria do Carmo; WRAMMERT, Jens; WHITEHEAD, Stephen S.; BURTON, Dennis R.; DESROSIERS, Ronald C.; KALLAS, Esper G.; WATKINS, David I.Exposure to dengue virus (DENV) is thought to elicit lifelong immunity, mediated by DENV-neutralizing antibodies (nAbs). However, Abs generated by primary infections confer serotype-specific protection, and immunity against other serotypes develops only after subsequent infections. Accordingly, the induction of these nAb responses acquired after serial DENV infections has been a long-sought-after goal for vaccination. Nonetheless, it is still unclear if tetravalent vaccines can elicit or recall nAbs. In this study, we have characterized the responses from a volunteer who had been previously exposed to DENV and was immunized with the live attenuated tetravalent vaccine Butantan-DV, developed by the NIH and Butantan Institute. Eleven days after vaccination, we observed an similar to 70-fold expansion of the plasmablast population. We generated 21 monoclonal Abs (MAbs) from singly sorted plasmablasts. These MAbs were the result of clonal expansions and had significant levels of somatic hypermutation (SHM). Nineteen MAbs (90.5%) neutralized at least one DENV serotype at concentrations of 1 mu g/ml or less; 6 of the 21 MAbs neutralized three or more serotypes. Despite the tetravalent composition of the vaccine, we observed a neutralization bias in the induced repertoire: DENV3 was targeted by 18 of the 19 neutralizing MAbs (nMAbs). Furthermore, the P3D05 nMAb neutralized DENV3 with extraordinary potency (concentration to achieve half-maximal neutralization [Neut(50)] = 0.03 mu g/ml). Thus, the Butantan-DV vaccine engendered a mature, antigen-selected B cell repertoire. Our results suggest that preexisting responses elicited by a previous DENV3 infection were recalled by immunization. IMPORTANCE The dengue epidemic presents a global public health challenge that causes widespread economic burden and remains largely unchecked by existing control strategies. Successful control of the dengue epidemic will require effective prophylactic and therapeutic interventions. Several vaccine clinical efficacy trials are approaching completion, and the chances that one or more live attenuated tetravalent vaccines (LATVs) will be introduced worldwide is higher than ever. While it is widely accepted that dengue virus (DENV)-neutralizing antibody (nAb) titers are associated with protection, the Ab repertoire induced by LATVs remain uncharacterized. Here, we describe the isolation of potent (Neut(50) < 0.1 mu g/ml) nAbs from a DENV-seropositive volunteer immunized with the tetravalent vaccine Butantan-DV, which is currently in phase III trials.