Browsing by Author "Duarte, Luisa"
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Publication Age and primary vaccination schedule impact humoral and cellular immunity with an inactivated SARS-CoV-2 vaccine(2025) Martínez, Yohana; Rodríguez, Linmar; Méndez, Constanza; Ríos, Mariana; Rivera, Daniela; Moreno, Daniela; Reyes, Humberto; Pereira, Patricia; Orellana, Claudia; Cabrera, Alex; Schultz, Bárbara; Duarte, Luisa; Gálvez, Nicolás; Melo, Felipe; Soto, Jorge; Iturriaga, Carolina; Urzúa, Marcela; Navarrete, Marıía; Rojas, Álvaro; Fasce, Rodrigo; Fernández, Jorge; Mora, Judith; Ramíez, Eugenio; Weiskopf, Daniela; Grifoni, Alba; Sette, Alessandro; Zeng, Gang; Meng, Weining; CoronaVac03CL Study Group; Alvarez, María; González, Jose; Domínguez, M. Angélica; González, Pablo; Abarca, Katia; Peñaloza, Hernán; Bueno, Susan; Kalergis, AlexisDespite widespread COVID-19 vaccination, questions remain about vaccine safety and immunogenicity in vulnerable populations, such as older adults. We evaluated the safety and immunogenicity of four doses of CoronaVac in adults above and below 60 who received the first two doses in two different schedules (0-14 and 0-28 days apart). While CoronaVac demonstrated excellent safety across age groups, older adults showed reduced reactogenicity. In the 0-28 schedule, both age groups exhibited similar frequencies of SARS-CoV-2-specific CD4+ and CD8+ T cells, though memory T cell distribution patterns differed. Notably, adults over 60 showed diminished virus-neutralizing antibody responses compared to younger participants. The 0-14 schedule produced equivalent cellular and neutralizing antibody responses between age groups, albeit at lower levels than the 0-28 schedule. Our data indicate that primary vaccination schedules can influence the humoral immune responses and memory T cell distribution between age groups.Publication Asymptomatic herpes simplex virus brain infection elicits cellular senescence phenotypes in the central nervous system of mice suffering multiple sclerosis-like disease(2024) Duarte, Luisa; Villalobos, Verónica; Farías, Mónica; Rangel, Maria; González, Enrique; Navarro, Areli; Carbone, Javier; Domínguez, Angélica; Alvarez, Alejandra; Riedel, Claudia; Bueno, Susan; Kalergis, Alexis; Cáceres, Mónica; González, PabloExperimental autoimmune encephalomyelitis (EAE) is a demyelinating disease affecting the central nervous system (CNS) in animals that parallels several clinical and molecular traits of multiple sclerosis in humans. Herpes simplex virus type 1 (HSV-1) infection mainly causes cold sores and eye diseases, yet eventually, it can also reach the CNS, leading to acute encephalitis. Notably, a significant proportion of healthy individuals are likely to have asymptomatic HSV-1 brain infection with chronic brain inflammation due to persistent latent infection in neurons. Because cellular senescence is suggested as a potential factor contributing to the development of various neurodegenerative disorders, including multiple sclerosis, and viral infections may induce a premature senescence state in the CNS, potentially increasing susceptibility to such disorders, here we examine the presence of senescence-related markers in the brains and spinal cords of mice with asymptomatic HSV-1 brain infection, EAE, and both conditions. Across all scenarios, we find a significant increases of senescence biomarkers in the CNS with some differences depending on the analyzed group. Notably, some senescence biomarkers are exclusively observed in mice with the combined conditions. These results indicate that asymptomatic HSV-1 brain infection and EAE associate with a significant expression of senescence biomarkers in the CNS.Publication Characterization of Hydrogel Beads for the Gradual Release of Origanum vulgare L. Essential Oil and Evaluation of Their Antifungal Activity Against Candida albicans(2025) Concha, Victoria; Díaz, Mario; Duarte, Luisa; Jara, José; Molina, AlfredoCandida albicans infections are associated with high morbidity and mortality worldwide. Current antifungal therapies are limited by adverse effects and the emergence of resistant strains, which compromise long-term efficacy. Previous studies have shown that Origanum vulgare L. essential oil (OvEO) possesses strong antifungal activity; however, its volatility and physicochemical instability hinder clinical application. The aim of this study was to encapsulate OvEO in a hydrogel and evaluate its release kinetics, chemical composition, structural properties, and antifungal activity. We assessed its release kinetics, chemical composition, structural characteristics (FTIR; SEM), and antifungal activity against C. albicans. OvEO was successfully encapsulated into hydrogel beads, enabling a gradual release profile, with in vitro release of phenolic compounds reaching 100% at 48 min. SEM revealed an irregular surface with small pores and crystalline aggregates distributed across the bead surface. OvEO-loaded hydrogel beads inhibited C. albicans growth with an IC50 of 0.15 ± 0.05 mg/L for strain 90029 and 0.2 ± 0.06 mg/L for strain 10231. At these concentrations, adhesion to abiotic surfaces was reduced by 60–80%. These findings support the potential of OvEO-loaded hydrogel beads as an alternative approach for the treatment of fungal infections, offering a complementary strategy to current antifungal agents.Publication Gestational hypothyroxinemia causes an inflammatory environment at maternal-fetal tissues and fetal brain with impaired hippocampal dendritic spine maturation in the offspring(2025) González, Enrique; Rangel, Andreina; Opazo, María; Espinoza, Sebastián; Elgueta, Daniela; Cancino, Gonzalo; Mery, Elena; Ardiles, Álvaro; Duarte, Luisa; Soto, Jorge; Carreño, Leandro; Simon, Felipe; Bueno, Susan; González, Pablo; Kalergis, AlexisGestational hypothyroxinemia (HTX) is associated with cognitive impairments and autism traits in offspring. However, the underlying mechanisms remain unclear. Prenatal inflammation impairs cortical development and induces diverse neurodevelopmental outcomes. Since thyroid dysfunction elicits inflammation, we sought to investigate whether HTX triggers prenatal pro-inflammatory responses. Using a mouse model of gestational HTX, we found elevated levels of IL-6 and IL-17 A in maternal serum, placental tissues, and embryonic brains at embryonic day (E)14 compared to euthyroid (EUT) dams. We also found increased proportions of dendritic cells, NK cells, M1-like macrophages, and monocytes in the placental tissues of HTX dams. Furthermore, gestational HTX exposure led to reduced Tbr2⁺ progenitors, increased Tbr1⁺ neurons, and an expanded Iba1⁺ microglial population in HTX-exposed embryos compared to EUT-exposed embryos. At postnatal day (P)55, the offspring gestated under HTX exhibited reduced hippocampal dendritic spine density and maturity compared to the progeny gestated under EUT. Notably, restoring T4 levels during HTX induction (HTX + T4 dams) prevented these alterations during pregnancy and in the offspring of HTX + T4 dams. These findings show that gestational HTX causes inflammation during pregnancy and has neurodevelopmental effects on the progeny, opening new pathways related to how maternal HTX impairs neurodevelopment in the offspring.Publication HSV-1 alters lipid metabolism and induces lipid droplet accumulation in functionally impaired mouse dendritic cells(2025) Farías, Mónica; Cancino, Felipe; Navarro, Areli; Duarte, Luisa; Soto, Abel; Tognarelli, Eduardo; Ramm, Maximiliano; Alarcón, Bárbara; Cordero, José; San Martín, Sergio; Agurto, Cristian; Retamal, Angello; Riedel, Claudia; Barrera, Nelson; Bustamante, Luis; Bueno, Susan; Kalergis, Alexis; González, PabloHerpes simplex virus type 1 (HSV-1) significantly impairs dendritic cell (DC) function, ultimately eliciting the death of these cells. Here, we sought to assess whether HSV-1 modulates lipid metabolism in mouse DCs as a mechanism of immune evasion. For this, we performed RT-qPCR gene arrays with ingenuity pathway analysis (IPA), RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA), confocal microscopy, transmission electron microscopy, ultra-high-performance liquid chromatography-quadrupole time-of-flight (UHPLC-QTOF) analysis, pharmacological inhibition of eight lipid-metabolism-related enzymes in HSV-1-infected DCs, co-cultures between virus-specific transgenic CD4+ and CD8+ T cells and HSV-1-infected DCs, and in vivo assays with mice. We found that HSV-1 significantly alters lipid metabolism in DCs and induces lipid droplet (LD) accumulation in these cells. Pharmacological inhibition of two particular lipid metabolism enzymes was found to partially restore DC function. Overall, these results suggest that lipid metabolism plays an important role in the impairment of DC function by HSV-1.Publication Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children(2022) Soto, Jorge; Melo, Felipe; Gutierrez, Cristián; Schultz, Bárbara; Berríos, Roslye; Rivera, Daniela; Piña, Alejandro; Hoppe, Guillermo; Duarte, Luisa; Vázquez, Yaneisi; Moreno, Daniela; Ríos, Mariana; Palacios, Pablo; Garcia, Richard; Santibañez, Álvaro; Pacheco, Gaspar; Mendez, Constanza; Andrade, Catalina; Silva, Pedro; Diethelm, Benjamín; Astudillo, Patricio; Calvo, Mario; Cárdenas, Antonio; González, Marcela; Goldsack, Macarena; Gutiérrez, Valentina; Potin, Marcela; Schilling, Andrea; Tapia, Lorena; Twele, Loreto; Villena, Rodolfo; Grifoni, Alba; Sette, Alessandro; Weiskopf, Daniela; Fasce, Rodrigo; Fernández, Jorge; Mora, Judith; Ramírez, Eugenio; Gaete, Aracelly; Acevedo, Mónica; Valiente, Fernando; Soto, Ricardo; Retamal, Angello; Muñoz, Nathalia; PedCoronaVac03CL Study Group; Meng, Xing; Xin, Qianqian; Alarcón, Eduardo; González, José; Le Corre, Nicole; Álvarez, María; González, Pablo; Abarca, Katia; Perret, Cecilia; Carreño, Leandro; Bueno, Susan; Kalergisa, AlexisMultiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD4+ T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD4+ T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD4+ T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials.gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD4+ T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron.Publication Therapeutic challenges in central nervous system viral infections: advancing mesenchymal stem cell-based strategies for treating neuroinflammation and promoting tissue repair(2025) Carbone, Javier; Fontecilla, Javiera; Sales, Nicolás; Chaparro, William; Molina, Alfredo; Ruete, María; González, Pablo; Machuca, Mayra; Opazo, Ma Cecilia; Ezquer, Marcelo; Duarte, LuisaAlthough significant progress has been made in medicine and antimicrobial research, viral infections continue to pose a critical global health challenge, particularly when they involve the central nervous system (CNS). Despite advances in vaccines, antiviral agents, and small molecule therapeutics, current strategies remain insufficient to address the complex consequences of many CNS infections fully. Notably, many viruses are neurotropic and can invade the CNS, triggering infectious neuroinflammation that often lead to chronic neurological disorders and lasting morbidity. Current therapeutic approaches are largely ineffective in preventing or reversing this long-term neurological damage, underscoring the urgent need for innovative prophylactic and therapeutic interventions. Mesenchymal stem cells (MSCs) have emerged as a promising strategy to counteract chronic neuroinflammation and promote tissue repair following viral CNS infections. This review provides a comprehensive overview of CNS viral infection and neuroinflammation, including epidemiology and pathophysiology, and critically examines the limitations of existing treatments, particularly their inability to mitigate persistent neurological sequelae. Furthermore, we summarize recent preclinical and clinical studies investigating the use of MSCs in the context of CNS viral infections, highlighting their immunomodulatory and neuroprotective mechanisms, and discuss the challenges and future directions for MSC-based therapies in clinical settings.