ALVINA CLARA FELIX
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
43 resultados
Resultados de Busca
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conferenceObject DENGUE IN SOUTHEASTERN BRAZIL: A LARGE OUTBREAK FOLLOWED BY A THREE-YEAR LOW INCIDENCE PERIOD. OBSERVATIONS FROM A PROSPECTIVE COHORT STUDY(2018) LUNA, Expedito; FIGUEIREDO, Gerusa; LEVI, Jose; CAMPOS, Sergio; FIGUEIREDO, Walter; COSTA, Angela; FELIX, Alvina; SOUZA, Nathalia; PANNUTI, Claudio- A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus(2017) MAGNANI, Diogo M.; SILVEIRA, Cassia G. T.; ROSEN, Brandon C.; RICCIARDI, Michael J.; PEDRENO-LOPEZ, Nuria; GUTMAN, Martin J.; BAILEY, Varian K.; MAXWELL, Helen S.; DOMINGUES, Aline; GONZALEZ-NIETO, Lucas; AVELINO-SILVA, Vivian I.; TRINDADE, Mateus; NOGUEIRA, Juliana; OLIVEIRA, Consuelo S.; MAESTRI, Alvino; FELIX, Alvina Clara; LEVI, Jose Eduardo; NOGUEIRA, Mauricio L.; MARTINS, Mauricio A.; MARTINEZ-NAVIO, Jose M.; FUCHS, Sebastian P.; WHITEHEAD, Stephen S.; BURTON, Dennis R.; DESROSIERS, Ronald C.; KALLAS, Esper G.; WATKINS, David I.The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient. One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation. This mAb neutralized ZIKV (Neut(50) similar to 2 mu g/ml) but did not react with any of the four dengue virus serotypes. Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes. This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation. Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting.
- DETECTION OF HUMAN ANTI-ZIKA VIRUS IgG BY ELISA USING AN ANTIGEN FROM in vitro INFECTED VERO CELLS: PRELIMINARY RESULTS(2016) SUMITA, Laura Masami; RODRIGUES, Jaqueline Polizeli; FERREIRA, Noely Evangelista; FELIX, Alvina Clara; SOUZA, Nathalia Caroline Santiago; MACHADO, Clarisse Martins; ANDRADE JUNIOR, Heitor Franco deZika virus (ZKV) infection is a huge public health problem in Brazil because of the increased incidence of microcephaly in neonates from infected mothers. Detection of specific IgG antibodies in maternal serum samples constitutes an important approach for diagnosing ZKV infection and evaluating its relationship with neonatal microcephaly. However, as there is no serological test produced in Brazil to detect IgM and IgG antibodies against ZKV, we sought to examine specific IgG in serum samples from patients or suspected mothers to detect previous infection and to test for specificity with regard to flaviviral infections occurring in the same area. Brazilian Zika virus native antigens were obtained from infected Vero cell layers or free virions in the culture medium and then used in ELISA. We tested sera from eight ZKV RNA-diagnosed infected patients (ZKVR), seven neonates with microcephaly and their mothers after delivery (MM), 140 dengue virus IgM-positive (DM) and IgG (DG)-positive patients, and 100 yellow fever (YF)-vaccinated patients. According to the ELISA, ZKVR samples were mostly positive (7/8), and all the MM serum samples were positive for ZKV IgG (7/7). In contrast, cross-reactions for dengue or yellow fever-vaccinated patients were observed, including DM (48/95), DG (10/45) or YF (3/100) serum samples; however, these cross-reactions exhibited low antigen avidity so that 6 M urea largely removed this cross-reactivity, with only a few cross-reacting samples remaining (8/140). ELISA based on extracted virions was much more specific, with all ZKVR (8/8) and MM sera being positive for ZKV IgG (7/7) and only borderline cross-reactivity found for DM (6/95), DG (3/45) or YF (4/100)-vaccinated serum samples. This technique (ELISA) can identify specific IgG in ZKV-infected patients and may be helpful in diagnosing congenital infetions after maternal RNA virus clearance or in epidemiological studies.
conferenceObject ZIKA VIRUS INFECTION IN A COHORT STUDY TO ASSESS THE INCIDENCE OF DENGUE, STATE OF SAO PAULO, BRAZIL, 2015, 2016(2017) FIGUEIREDO, Gerusa M.; LUNA, Expedito J.; CARDOSO, Maria Regina; LEVI, Jose E.; FELIX, Alvina C.; SOUZA, Nathalia C. C.; SOUZA, Ana C.; CAMPOS, Sergio R. Campos R.; FIGUEIREDO, Walter M.; COSTA, Angela A.; PANNUTI, Claudio S.- Cross reactivity of commercial anti-dengue immunoassays in patients with acute Zika virus infection(2017) FELIX, Alvina Clara; SOUZA, Nathalia C. Santiago; FIGUEIREDO, Walter M.; COSTA, Angela A.; INENAMI, Marta; SILVA, Rosangela M. G. da; LEVI, Jose Eduardo; PANNUTI, Claudio Sergio; ROMANO, Camila MaltaSeveral countries have local transmission of multiple arboviruses, in particular, dengue and Zika viruses, which have recently spread through many American countries. Cross reactivity among Flaviviruses is high and present a challenge for accurate identification of the infecting agent. Thus, we evaluated the level of cross reactivity of anti-dengue IgM/G Enzyme-Linked Immunosorbent Assays (ELISA) from three manufacturers against 122 serum samples obtained at two time-points from 61 patients with non-dengue confirmed Zika virus infection. All anti-dengue ELISAs cross reacted with serum from patients with acute Zika infection at some level and a worrisome number of seroconversion for dengue IgG and IgM was observed. These findings may impact the interpretation of currently standard criteria for dengue diagnosis in endemic regions.
- Dengue Virus Serotype 2 Intrahost Diversity in Patients with Different Clinical Outcomes(2021) TORRES, Maria Celeste; MENDONCA, Marcos Cesar Lima de; RODRIGUES, Cintia Damasceno dos Santos; FONSECA, Vagner; RIBEIRO, Mario Sergio; BRANDAO, Ana Paula; CUNHA, Rivaldo Venancio da; DIAS, Ana Isabel; BOAS, Lucy Santos Vilas; FELIX, Alvina Clara; PEREIRA, Maira Alves; PINTO, Luzia Maria de Oliveira; SAKUNTABHAI, Anavaj; FILIPPIS, Ana Maria Bispo deIntrahost genetic diversity is thought to facilitate arbovirus adaptation to changing environments and hosts, and it might also be linked to viral pathogenesis. Dengue virus serotype 2 (DENV-2) has circulated in Brazil since 1990 and is associated with severe disease and explosive outbreaks. Intending to shed light on the viral determinants for severe dengue pathogenesis, we sought to analyze the DENV-2 intrahost genetic diversity in 68 patient cases clinically classified as dengue fever (n = 31), dengue with warning signs (n = 19), and severe dengue (n = 18). Unlike previous DENV intrahost diversity studies whose approaches employed PCR, here we performed viral whole-genome deep sequencing from clinical samples with an amplicon-free approach, representing the real intrahost diversity scenario. Striking differences were detected in the viral population structure between the three clinical categories, which appear to be driven mainly by different infection times and selection pressures, rather than being linked with the clinical outcome itself. Diversity in the NS2B gene, however, showed to be constrained, irrespective of clinical outcome and infection time. Finally, 385 non-synonymous intrahost single-nucleotide variants located along the viral polyprotein, plus variants located in the untranslated regions, were consistently identified among the samples. Of them, 124 were exclusively or highly detected among cases with warning signs and among severe cases. However, there was no variant that by itself appeared to characterize the cases of greater severity, either due to its low intrahost frequency or the conservative effect on amino acid substitution. Although further studies are necessary to determine their real effect on viral proteins, this heightens the possibility of epistatic interactions. The present analysis represents an initial effort to correlate DENV-2 genetic diversity to its pathogenic potential and thus contribute to understanding the virus's dynamics within its human host.
- MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection(2018) PAQUIN-PROULX, Dominic; AVELINO-SILVA, Vivian I.; SANTOS, Bianca A. N.; BARSOTTI, Nathalia Silveira; SIROMA, Fabiana; RAMOS, Jessica Fernandes; TONACIO, Adriana Coracini; SONG, Alice; MAESTRI, Alvino; CERQUEIRA, Natalia Barros; FELIX, Alvina Clara; LEVI, Jose Eduardo; GREENSPUN, Benjamin C.; ROUGVIE, Miguel de Mulder; ROSENBERG, Michael G.; NIXON, Douglas F.; KALLAS, Esper G.Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are pre-dominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barre A syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFN gamma response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFN gamma in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.
conferenceObject A COHORT STUDY TO DETERMINE THE INCIDENCE OF ZIKA VIRUS INFECTION AMONG NEWBORNS, SANTOS, BRAZIL, 2016-2017(2017) LUNA, Expedito J.; ROMANO, Camila M.; ARAUJO, Evaldo S.; LEVI, Jose E.; OLIVEIRA, Olimpia N.; FERNANDES, Luis R.; FELIX, Alvina C.; SOUZA, Nathalia S.; FERNANDES, Joao H.; CAMPOS, Sergio R.; FRAGOSO, Danielli B.; PANNUTI, Claudio S.- Zika and chikungunya virus infections in hematopoietic stem cell transplant recipients and oncohematological patients(2017) MACHADO, Clarisse Martins; PEREIRA, Barbara Brito de Souza; FELIX, Alvina Clara; OLIVEIRA, Maria Carolina; DARRIGO JR., Luiz Guilherme; SOUZA, Mair Pedro de; PATON, Eduardo Jose de Alencar; NEVES, Fabia; COLTURATO, Vergilio Rensi; SIMOES, Belinda PintoAedes mosquitoes are well adapted in domestic environments and widespread in tropical regions. Since 2015, Brazil has been experiencing a triple epidemic of dengue (DENV), chikungunya (CHKV), and Zika (ZIKV) viruses. The last 2 viruses are likely following the path of DENV, which has been endemic in most parts of the country since the 1980s. Given this triple epidemic, we proposed a prospective and collaborative study to assess the prevalence, morbidity, andmortality of DENV, CHKV, and ZIKV infections in hematopoietic stem cell transplant (HSCT) recipients and oncohematological patients. A case definition strategy (fever and rash) was used to prompt diagnostic investigation of DENV, ZIKV, and CHKV, which was accomplished by real-time polymerase chain reaction with plasma and urine samples. Clinical follow-up was performed 7 and 30 days after symptom onset. We report here the first cases of ZIKV and CHKV infections diagnosed in this ongoing study. From February to May 2016, 9 of the 26 patients (34.6%) fulfilling case definition criteria were diagnosed with DENV (3 cases), ZIKV (4 cases), or CHKV (2 cases) infections. Prolonged viremia and viruria were observed in dengue and Zika fever cases, respectively. Thrombocytopenia was the most frequent complication. Delayed engraftment was noted in 1 patient who acquired ZIKV 25 days before HSCT. All patients survived without sequelae. With the geographic expansion of arboviruses, donor and recipient screening may become mandatory. Patients living in areas where these viruses are not endemic are also at risk, since these viruses can be transmitted by blood as well as organ or tissue transplantation
- Phylogenetics, Epidemiology and Temporal Patterns of Dengue Virus in Araraquara, São Paulo State(2024) SOUZA, Caio Santos de; CALEIRO, Giovana Santos; CLARO, Ingra Morales; JESUS, Jaqueline Goes de; COLETTI, Thais Moura; SILVA, Camila Alves Maia da; COSTA, Angela Aparecida; INENAMI, Marta; RIBEIRO, Andreia C.; FELIX, Alvina Clara; PAULA, Anderson Vicente de; FIGUEIREDO, Walter M.; LUNA, Expedito Jose de Albuquerque; SABINO, Ester C.; ROMANO, Camila M.Dengue virus (DENV) is a prominent arbovirus with global spread, causing approximately 390 million infections each year. In Brazil, yearly epidemics follow a well-documented pattern of serotype replacement every three to four years on average. Araraquara, located in the state of Sao Paulo, has faced significant impacts from DENV epidemics since the emergence of DENV-1 in 2010. The municipality then transitioned from low to moderate endemicity in less than 10 years. Yet, there remains an insufficient understanding of virus circulation dynamics, particularly concerning DENV-1, in the region, as well as the genetic characteristics of the virus. To address this, we sequenced 37 complete or partial DENV-1 genomes sampled from 2015 to 2022 in Araraquara. Then, using also Brazilian and worldwide DENV-1 sequences we reconstructed the evolutionary history of DENV-1 in Araraquara and estimated the time to the most recent common ancestor (tMRCA) for serotype 1, for genotype V and its main lineages. Within the last ten years, there have been at least three introductions of genotype V in Araraquara, distributed in two main lineages (L Ia and L Ib, and L II). The tMRCA for the first sampled lineage (2015/2016 epidemics) was approximately 15 years ago (in 2008). Crucially, our analysis challenges existing assumptions regarding the emergence time of the DENV-1 genotypes, suggesting that genotype V might have diverged more recently than previously described. The presence of the two lineages of genotype V in the municipality might have contributed to the extended persistence of DENV-1 in the region.