LUANA DE MENDONCA OLIVEIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
15 resultados
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- Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants(2024) TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; BRANCO, Anna Claudia Calvielli Castelo; ALBERCA, Ricardo Wesley; SOUSA, Emanuella Sarmento Alho de; LEITE, Bruno Henrique de Sousa; ADAN, Wenny Camilla dos Santos; DUARTE, Alberto Jose da Silva; LINS, Roberto Dias; SATO, Maria Notomi; VIANA, Isabelle Freire TabosaZika virus (ZIKV) is a re-emerging pathogen with high morbidity associated to congenital infection. Despite the scientific advances since the last outbreak in the Americas, there are no approved specific treatment or vaccines. As the development of an effective prophylactic approach remains unaddressed, DNA vaccines surge as a powerful and attractive candidate due to the efficacy of sequence optimization in achieving strong immune response. In this study, we developed four DNA vaccine constructs encoding the ZIKV prM/M (pre-membrane/membrane) and E (envelope) proteins in conjunction with molecular adjuvants. The DNA vaccine candidate (called ZK_Delta STP), where the entire membrane-anchoring regions were completely removed, was far more immunogenic compared to their counterparts. Furthermore, inclusion of the tPA-SP leader sequence led to high expression and secretion of the target vaccine antigens, therefore contributing to adequate B cell stimulation. The ZK_Delta STP vaccine induced high cellular and humoral response in C57BL/6 adult mice, which included high neutralizing antibody titers and the generation of germinal center B cells. Administration of ZK-Delta STP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_Delta STP+Alum protected adult mice upon viral challenge. Collectively, the ZK_Delta STP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies.
- Tolerogenic microenvironment in neonatal period induced by maternal immunization with ovalbumin(2014) MUNIZ, Bruno Pacola; VICTOR, Jefferson Russo; OLIVEIRA, Luana de Mendonca; LIRA, Aline Aparecida de Lima; PERINI, Adenir; OLIVO, Clarice Rosa; ARANTES-COSTA, Fernanda Magalhaes; MARTINS, Milton Arruda; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiMaternal immunization with allergens, such as ovalbumin (OVA), can inhibit the development of an allergic response in offspring. The regulatory mechanisms seem to be mediated by maternal antibodies (MatAbs) and factors generated by the maternal fetal interface. The aim of this study was to verify the pathways of inhibitory Ab transference after maternal immunization with OVA and the effect of the offspring's dendritic cells (DCs) on the generation of regulatory T (Treg) cells. We verified that preconceptional OVA immunization induces high levels of proinflammatory and regulatory cytokines in the amniotic fluid, allowing the transference of high levels of anti-OVA IgG1 Abs to the offspring. Using an adoptive nursing protocol, we verified that maternal immunization leads to MatAb transference by the placental route and by breastfeeding contribute to the inhibition of anaphylactic IgE and IgG1 Ab responses in immunized offspring. We observed that maternal immunization decreased eosinophil numbers in recovered bronchoalveolar lavage fluid and in the lung tissue, whereas with a lack of control of airway responsiveness to methacholine. Maternal immunization induced in young offspring a decreased percentage of CD11c+ DCs expressing MHC class II and CD40 molecules. Moreover, DCs from both groups of offspring when pulsed with OVA, were able to induce Treg cells in vitro. Similarly, OVA immunization at the neonatal stage increased the frequency of Treg cells, regardless of the mother's immunization status. These findings emphasize that maternal immunization leads to a complex interaction of regulatory factors, with MatAbs, DCs and Treg cells affecting the tolerance of offspring during an allergic response.
- LAMP-1 Chimeric to HIV-1 p55Gag in the Immunization of Neonate Mice Induces an Early Germinal Center Formation and AID Expression(2022) TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; PIETROBON, Anna Julia; SALLES, Erika Machado de; LIMA, Maria Regina D'Imperio; VIANA, Isabelle Freire Tabosa; LINS, Roberto Dias; RIGATO, Paula Ordonhez; MARQUES, Ernesto Torres de Azevedo; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiNeonates have a limited adaptive response of plasma cells, germinal center (GC) B cells, and T follicular helper cells (T-FH). As neonatal vaccination can be an important tool for AIDS prevention, these limitations need to be overcome. Chimeric DNA vaccine encoding p55Gag HIV-1 protein conjugated with lysosomal-associated membrane protein 1 (LAMP-1) has been described as immunogenic in the neonate period. Herein, we investigated the immunologic mechanisms involved in neonatal immunization with a LAMP-1/p55Gag (LAMP/Gag) DNA vaccine in a C57BL/6 mouse background. Neonatal LAMP/Gag vaccination induced strong Gag-specific T-cell response until adulthood and elevated levels of anti-Gag IgG antibodies. We also demonstrated for the first time that the immunogenicity of the neonatal period with LAMP/Gag is due to the induction of high-affinity anti-p24 IgG antibodies and long-term plasma cells. Together with that, there is the generation of early TFH cells and the formation of GC sites with the upregulation of activation-induced cytidine deaminase (AID) enzyme mRNA and protein expression in draining lymph nodes after neonatal LAMP/Gag vaccination. These findings underscore that the LAMP-1 strategy in the chimeric vaccine could be useful to enhance antibody production even in the face of neonatal immaturity, and they contribute to the development of new vaccine approaches for other emerging pathogens at an early stage of life.
- Generation of Cytotoxic T Cells and Dysfunctional CD8 T Cells in Severe COVID-19 Patients(2022) GOZZI-SILVA, Sarah Cristina; OLIVEIRA, Luana de Mendonca; ALBERCA, Ricardo Wesley; PEREIRA, Natalli Zanete; YOSHIKAWA, Fabio Seiti; PIETROBON, Anna Julia; YENDO, Tatiana Mina; ANDRADE, Milena Mary de Souza; RAMOS, Yasmim Alefe Leuzzi; BRITO, Cyro Alves; OLIVEIRA, Emily Araujo; BESERRA, Danielle Rosa; ORFALI, Raquel Leao; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCOVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The viral infection can evolve asymptomatically or can generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia based on the severity of symptoms in patients affected with COVID-19 is frequent. However, the profiles of CD4+ and CD8+ T cells regarding cytotoxicity and antiviral factor expression have not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study was to evaluate the phenotypic and functional profile of T lymphocytes in patients with moderate and severe/critical COVID-19. During the pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Notwithstanding lymphopenia, we observed an increase in the expression of CD28, a co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T lymphocytes as well as an increase in the frequency of CD4+ T cells, CD8+ T cells, and NK cells that express the immunological checkpoint protein PD-1 in patients with a severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T cells was already observed at the baseline level and scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T lymphocytes decreased the cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed by t-SNE, there were CD4+ T-cytotoxic and CD8+ T with low granzyme production, evidencing their dysfunction in severe/critical conditions. In addition, purified CD8+ T lymphocytes from patients with severe COVID-19 showed increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and, curiously, had reduced expression of TNF-alpha. The cytotoxic profile of CD4+ T cells may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T cells and CD8+ T cells in the severity of acute COVID-19 infection.
- COVID-19 Disease Course in Former Smokers, Smokers and COPD Patients(2021) ALBERCA, Ricardo Wesley; LIMA, Julia Cataldo; OLIVEIRA, Emily Araujo de; GOZZI-SILVA, Sarah Cristina; RAMOS, Yasmim Alefe Leuzzi; ANDRADE, Milena Mary de Souza; BESERRA, Danielle Rosa; OLIVEIRA, Luana de Mendonca; BRANCO, Anna Claudia Calvielli Castelo; PIETROBON, Anna Julia; PEREIRA, Natalli Zanete; TEIXEIRA, Franciane Mouradian Emidio; FERNANDES, Iara Grigoletto; DUARTE, Alberto Jose da Silva; BENARD, Gil; SATO, Maria NotomiThe severe respiratory and systemic disease named coronavirus disease-2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, the COVID-19 pandemic presents a huge social and health challenge worldwide. Many different risk factors are associated with disease severity, such as systemic arterial hypertension, diabetes mellitus, obesity, older age, and other co-infections. Other respiratory diseases such as chronic obstructive pulmonary disease (COPD) and smoking are common comorbidities worldwide. Previous investigations have identified among COVID-19 patients smokers and COPD patients, but recent investigations have questioned the higher risk among these populations. Nevertheless, previous reports failed to isolate smokers and COPD patients without other comorbidities. We performed a longitudinal evaluation of the disease course of smokers, former smokers, and COPD patients with COVID-19 without other comorbidities, from hospitalization to hospital discharge. Although no difference between groups was observed during hospital admission, smokers and COPD patients presented an increase in COVID-19-associated inflammatory markers during the disease course in comparison to non-smokers and former smokers. Our results demonstrated that smoking and COPD are risk factors for severe COVID-19 with possible implications for the ongoing pandemic.
- SARS-CoV-2 Infection and CMV Dissemination in Transplant Recipients as a Treatment for Chagas Cardiomyopathy: A Case Report(2021) GOZZI-SILVA, Sarah Cristina; BENARD, Gil; ALBERCA, Ricardo Wesley; YENDO, Tatiana Mina; TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; BESERRA, Danielle Rosa; PIETROBON, Anna Julia; OLIVEIRA, Emily Araujo de; BRANCO, Anna Claudia Calvielli Castelo; ANDRADE, Milena Mary de Souza; FERNANDES, Iara Grigoletto; PEREIRA, Natalli Zanete; RAMOS, Yasmim Alefe Leuzzi; LIMA, Julia Cataldo; PROVENCI, Bruna; MANGINI, Sandrigo; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has infected over 90 million people worldwide, therefore it is considered a pandemic. SARS-CoV-2 infection can lead to severe pneumonia, acute respiratory distress syndrome (ARDS), septic shock, and/or organ failure. Individuals receiving a heart transplantation (HT) may be at higher risk of adverse outcomes attributable to COVID-19 due to immunosuppressives, as well as concomitant infections that may also influence the prognoses. Herein, we describe the first report of two cases of HT recipients with concomitant infections by SARS-CoV-2, Trypanosoma cruzi, and cytomegalovirus (CMV) dissemination, from the first day of hospitalization due to COVID-19 in the intensive care unit (ICU) until the death of the patients.
- Platelet-Based Biomarkers for Diagnosis and Prognosis in COVID-19 Patients(2021) ALBERCA, Ricardo Wesley; SOLIS-CASTRO, Rosa Liliana; SOLIS-CASTRO, Maria Edith; CARDOSO, Fernanda; DUARTE, Alberto Jose da Silva; OLIVEIRA, Luana de Mendonca; PEREIRA, Natalli Zanete; GOZZI-SILVA, Sarah Cristina; OLIVEIRA, Emily Araujo de; AOKI, Valeria; ORFALI, Raquel Leao; BESERRA, Danielle Rosa; ANDRADE, Milena Mary de Souza; SATO, Maria NotomiCoronavirus disease 2019 (COVID-19) caused millions of deaths worldwide. COVID-19's clinical manifestations range from no symptoms to a severe acute respiratory syndrome, which can result in multiple organ failure, sepsis, and death. Severe COVID-19 patients develop pulmonary and extrapulmonary infections, with a hypercoagulable state. Several inflammatory or coagulatory biomarkers are currently used with predictive values for COVID-19 severity and prognosis. In this manuscript, we investigate if a combination of coagulatory and inflammatory biomarkers could provide a better biomarker with predictive value for COVID-19 patients, being able to distinguish between patients that would develop a moderate or severe COVID-19 and predict the disease outcome. We investigated 306 patients with COVID-19, confirmed by severe acute respiratory syndrome coronavirus 2 RNA detected in the nasopharyngeal swab, and retrospectively analyzed the laboratory data from the first day of hospitalization. In our cohort, biomarkers such as neutrophil count and neutrophil-to-lymphocyte ratio from the day of hospitalization could predict if the patient would need to be transferred to the intensive care unit but failed to identify the patients & PRIME; outcomes. The ratio between platelets and inflammatory markers such as creatinine, C-reactive protein, and urea levels is associated with patient outcomes. Finally, the platelet/neutrophil-to-lymphocyte ratio on the first day of hospitalization can be used with predictive value as a novel severity and lethality biomarker in COVID-19. These new biomarkers with predictive value could be used routinely to stratify the risk in COVID-19 patients since the first day of hospitalization.
- Upregulation of PD-1 Expression and High sPD-L1 Levels Associated with COVID-19 Severity(2022) BESERRA, Danielle Rosa; ALBERCA, Ricardo Wesley; BRANCO, Anna Claudia Calvielli Castelo; OLIVEIRA, Luana de Mendonca; ANDRADE, Milena Mary de Souza; GOZZI-SILVA, Sarah Cristina; TEIXEIRA, Franciane Mouradian Emidio; YENDO, Tatiana Mina; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCOVID-19 has several mechanisms that can lead to lymphocyte depletion/exhaustion. The checkpoint inhibitor molecule programmed death protein 1 (PD-1) and its programmed death-ligand 1 (PDL-1) play an important role in inhibiting cellular activity as well as the depletion of these cells. In this study, we evaluated PD-1 expression in TCD4+, TCD8+, and CD19+ lymphocytes from SARS-CoV-2-infected patients. A decreased frequency of total lymphocytes and an increased PD-1 expression in TCD4+ and CD19+ lymphocytes were verified in severe/critical COVID-19 patients. In addition, we found a decreased frequency of total monocytes with an increased PD-1 expression on CD14+ monocytes in severe/critical patients in association with the time of infection. Moreover, we observed an increase in sPD-L1 circulant levels associated with the severity of the disease. Overall, these data indicate an important role of the PD-1/PDL-1 axis in COVID-19 and may provide a severity-associated biomarker and therapeutic target during SARS-CoV-2 infection.
- Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients(2022) PIETROBON, Anna Julia; ANDREJEW, Roberta; CUSTODIO, Ricardo Wesley Alberca; OLIVEIRA, Luana de Mendonca; SCHOLL, Juliete Nathali; TEIXEIRA, Franciane Mouradian Emidio; BRITO, Cyro Alves de; GLASER, Talita; KAZMIERSKI, Julia; GOFFINET, Christine; TURDO, Anna Claudia; YENDO, Tatiana; AOKI, Valeria; FIGUEIRO, Fabricio; BATTASTINI, Ana Maria; ULRICH, Henning; BENARD, Gill; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiEctonucleotidases modulate inflammatory responses by balancing extracellular ATP and adenosine (ADO) and might be involved in COVID-19 immunopathogenesis. Here, we explored the contribution of extracellular nucleotide metabolism to COVID-19 severity in mild and severe cases of the disease. We verified that the gene expression of ectonucleotidases is reduced in the whole blood of patients with COVID-19 and is negatively correlated to levels of CRP, an inflammatory marker of disease severity. In line with these findings, COVID-19 patients present higher ATP levels in plasma and reduced levels of ADO when compared to healthy controls. Cell type-specific analysis revealed higher frequencies of CD39+ T cells in severely ill patients, while CD4+ and CD8+ expressing CD73 are reduced in this same group. The frequency of B cells CD39+CD73+ is also decreased during acute COVID-19. Interestingly, B cells from COVID-19 patients showed a reduced capacity to hydrolyze ATP into ADP and ADO. Furthermore, impaired expression of ADO receptors and a compromised activation of its signaling pathway is observed in COVID-19 patients. The presence of ADO in vitro, however, suppressed inflammatory responses triggered in patients' cells. In summary, our findings support the idea that alterations in the metabolism of extracellular purines contribute to immune dysregulation during COVID-19, possibly favoring disease severity, and suggest that ADO may be a therapeutic approach for the disease.
- Frequencies of CD33+CD11b+HLA-DR-CD14-CD66b+and CD33+CD11b+HLA-DR-CD14+CD66b-Cells in Peripheral Blood as Severity Immune Biomarkers in COVID-19(2020) ALBERCA, Ricardo Wesley; ANDRADE, Milena Mary de Souza; BRANCO, Anna Claudia Calvielli Castelo; PIETROBON, Anna Julia; PEREIRA, Natalli Zanete; FERNANDES, Iara Grigoletto; OLIVEIRA, Luana de Mendonca; TEIXEIRA, Franciane Mouradian Emidio; BESERRA, Danielle Rosa; OLIVEIRA, Emily Araujo de; GOZZI-SILVA, Sarah Cristina; RAMOS, Yasmim Alefe Leuzzi; BRITO, Cyro Alves de; ARNONE, Marcelo; ORFALI, Raquel Leao; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCommon clinical features of patients with Coronavirus disease-2019 (COVID-19) vary from fever, to acute severe respiratory distress syndrome. Several laboratory parameters are reported as indicators of COVID-19 severity. We hereby describe the possible novel severity biomarkers for COVID-19, CD11b+CD33+HLA-DR-CD14+ cells and CD11b+CD33+HLA-DR-CD66b+ cells.