Browsing by Author "Bueno, Susan"
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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 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 Safety and Non-Inferiority Evaluation of Two Immunization Schedules with an Inactivated SARS-CoV-2 Vaccine in Adults: A Randomized Clinical Trial(2022) Abarca, Katia; Iturriaga, Carolina; Urzúa, Marcela; Le Corre, Nicole; Pineda, Augusto; Fernández, Carolina; Domínguez, Angélica; González, Pablo; Bueno, Susan; Donato, Paulina; Espinoza, Pilar; Fuentes, Daniela; González, Marcela; Guzmán, Paula; Muñoz Venturelli, Paula; Pérez, Carlos; Potin, Marcela; Rojas, Álvaro; González, José; Gálvez, Nicolás; Aguirre, Francisca; Aljaro, Sofía; Bátiz, Luis; Campisto, Yessica; Cepeda, Mariela; Cortés, Aarón; López, Sofía; Pérez, María; Schilling, Andrea; Kalergis, Alexis; On behalf of the CoronaVac CL Study GroupSeveral vaccines have been developed to control the COVID-19 pandemic. CoronaVac®, an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity, preventing severe COVID-19 cases. We investigate the safety and non-inferiority of two immunization schedules of CoronaVac® in a non-inferiority trial in healthy adults. A total of 2302 healthy adults were enrolled at 8 centers in Chile and randomly assigned to two vaccination schedules, receiving two doses with either 14 or 28 days between each. The primary safety and efficacy endpoints were solicited adverse events (AEs) within 7 days of each dose, and comparing the number of cases of SARS-CoV-2 infection 14 days after the second dose between the schedules, respectively. The most frequent local AE was pain at the injection site, which was less frequent in participants aged ≥60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. Most AEs were mild and transient. There were no significant differences for local and systemic AEs between schedules. A total of 58 COVID-19 cases were confirmed, and all but 2 of them were mild. No differences were observed in the proportion of COVID-19 cases between schedules. CoronaVac® is safe, especially in ≥60-year-old participants. Both schedules protected against COVID-19 hospitalization.