Browsing by Author "Urzua, Marcela"
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- ItemA Booster Dose of CoronaVac Increases Neutralizing Antibodies and T Cells that Recognize Delta and Omicron Variants of Concern(2022) Schultz, Barbara M.; Melo-Gonzalez, Felipe; Duarte, Luisa F.; Galvez, Nicolas M. S.; Pacheco, Gaspar A.; Soto, Jorge A.; Berrios-Rojas, Roslye, V; Gonzalez, Liliana A.; Moreno-Tapia, Daniela; Rivera-Perez, Daniela; Rios, Mariana; Vazquez, Yaneisi; Hoppe-Elsholz, Guillermo; Andrade-Parra, Catalina A.; Vallejos, Omar P.; Pina-Iturbe, Alejandro; Iturriaga, Carolina; Urzua, Marcela; Navarrete, Maria S.; Rojas, Alvaro; Fasce, Rodrigo; Fernandez, Jorge; Mora, Judith; Ramirez, Eugenio; Gaete-Argel, Aracelly; Acevedo, Monica; Valiente-Echeverria, Fernando; Soto-Rifo, Ricardo; Weiskopf, Daniela; Grifoni, Alba; Sette, Alessandro; Zeng, Gang; Meng, Weining; Gonzalez-Aramundiz, Jose, V; Gonzalez, Pablo A.; Abarca, Katia; Kalergis, Alexis M.; Bueno, Susan M.CoronaVac is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization (WHO). Previous studies reported increased levels of neutralizing antibodies and specific T cells 2 and 4 weeks after two doses of CoronaVac; these levels were significantly reduced at 6 to 8 months after the two doses. Here, we report the effect of a booster dose of CoronaVac on the anti-SARS-CoV-2 immune response generated against the variants of concern (VOCs), Delta and Omicron, in adults participating in a phase III clinical trial in Chile. Volunteers immunized with two doses of CoronaVac in a 4-week interval received a booster dose of the same vaccine between 24 and 30 weeks after the second dose. Neutralization capacities and T cell activation against VOCs Delta and Omicron were assessed 4 weeks after the booster dose. We observed a significant increase in neutralizing antibodies 4 weeks after the booster dose. We also observed a rise in anti-SARS-CoV-2-specific CD4(+) T cells over time, and these cells reached a peak 4 weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2-specific T cells induced by the booster showed activity against VOCs Delta and Omicron. Our results show that a booster dose of CoronaVac increases adults' humoral and cellular anti-SARS-CoV-2 immune responses. In addition, immunity induced by a booster dose of CoronaVac is active against VOCs, suggesting adequate protection. IMPORTANCE CoronaVac is an inactivated vaccine against SARS-CoV-2 that has been approved by WHO for emergency use. Phase III clinical trials are in progress in several countries, including China, Brazil, Turkey, and Chile, and have shown safety and immunogenicity after two doses of the vaccine. This report characterizes immune responses induced by two doses of CoronaVac followed by a booster dose 5 months after the second dose in healthy Chilean adults. The data reported here show that a booster dose increased the immune responses against SARS-CoV-2, enhancing levels of neutralizing antibodies against the ancestral strain and VOCs. Similarly, anti-SARS-CoV-2 CD4(+) T cell responses were increased following the booster dose. In contrast, levels of gamma interferon secretion and T cell activation against the VOCs Delta and Omicron were not significantly different from those for the ancestral strain. Therefore, a third dose of CoronaVac in a homologous vaccination schedule improves its immunogenicity in healthy volunteers.
- ItemBlends based on amino acid functionalized poly (ethylene-alt-maleic anhydride) polyelectrolytes and PEO for nanofiber elaboration: Biocompatible and angiogenic polyelectrolytes(2022) Leal, Matias; Leiva, Angel; Villalobos, Valeria; Palma, Veronica; Carrillo, Daniela; Edwards, Natalie; Maine, Arianne; Cauich-Rodriguez, Juan, V; Tamayo, Laura; Neira-Carrillo, Andronico; Urzua, MarcelaA wide variety of polymers have been electrospun to obtain nanofibers. However, obtaining nanofibers from polyelectrolytes is less frequent due to the charges of these polymers, which hinder the electrospinning process. Poly (ethylene-alt-maleic anhydride) (PEMA) was modified with a series of amino acids (Aa). The functionalization of PEMA with Aa (PEMA-Aa) was demonstrated by FT-IR, H-1 NMR, and C-13 NMR. Blends of PEMA-Aa and poly (ethylene oxide), PEO, with different ratios were prepared. Nanofibers were obtained by electrospinning using blends of 10-20% w/v of PEMA-Aa and 10% w/v of PEO. The conductivity of blends decreased, and the surface tension increased as the quantity of PEO in the blends was increased. TGA showed intermediate thermal properties compared with the blend components. Nanofibers were obtained for all PEMA-Aa/PEO blends, with diameters between 170 and 350 nm. Continuous fibers without morphological defects were obtained at concentrations of 20% w/v and 10% w/v of PEMA-Aa and PEO. Wharton's Jelly Mesenchymal Stem Cells viability, chicken embryo chorioallantoic membrane (CAM) assay and embryo viability measurements were realized for PEMA-Aa. Cytotoxicity test showed both composition and concentration-dependent behavior for PEMA-Aa, with higher WJ-MSC viability at 0.1 mg/mL at 24 h. CAM assay showed the formation of a high number of blood vessels and chicken embryo viability was close to 100% in the presence of polyelectrolytes. This, study demonstrates that electrospun nanofibers obtained from PEMA-Aa/PEO modified polyelectrolyte blends can be considered as a promising material for biomedical applications.
- ItemConformational Changes of Poly(Maleic Anhydride-alt-styrene) Modified with Amino Acids in an Aqueous Medium and Their Effect on Cytocompatibility and Hemolytic Response(2023) Maine, Arianne; Tamayo, Laura; Leiva, Angel; Gonzalez, Alex; Rios, Hernan E.; Rojas-Romo, Carlos; Jara, Paul; Araya-Duran, Ingrid; Gonzalez-Nilo, Fernando; Yazdani-Pedram, Mehrdad; Santana, Paula; Leal, Matias; Gonzalez, Nicolas; Briones, Ximena; Villalobos, Valeria; Urzua, MarcelaThe conformational changes of poly-(maleic anhydride-alt-styrene) (PSMA) modified with different amino acids (PSMA-Aa) were studied in an aqueous medium as a function of ionic strength and pH. The specific viscosity of PSMA-Aa decreased with increasing salt concentration due to a more compact conformation. There was a decrease in surface tension with increasing concentrations of the modified polyelectrolyte having a greater effect for the PSMA modified with l-phenylalanine at pH 7.0, demonstrating a greater surface-active character. The conformational changes were also confirmed by molecular dynamics studies, indicating that PSMA-Aa exhibits a compact structure at pH 4.0 and a more extended structure at pH 7.0. On the other hand, the conformational changes of PSMA-Aa were related to its biological response, where the higher surface-active character of the PSMA modified with l-phenylalanine correlates very well with the higher hemolytic activity observed in red blood cells, in which the surface-active capacity supports lytic potency in erythrocytes. The cytocompatibility assays indicated that there were no significant cytotoxic effects of the PSMA-Aa. Additionally, in solvent-accessible surface area studies, it was shown that the carboxylate groups of the PSMA modified with l-phenylalanine are more exposed to the solvent at pH 7.0 and high salt concentrations, which correlates with lower fluorescence intensity, reflecting a loss of mitochondrial membrane potential. It is concluded that the study of the conformational changes in PE modified with amino acids is essential for their use as biomaterials and relevant to understanding the possible effects of PE modified with amino acids in biological systems.
- ItemDifferences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial(2022) Galvez, Nicolas M. S.; Pacheco, Gaspar A.; Schultz, Barbara M.; Melo-Gonzalez, Felipe; Soto, Jorge A.; Duarte, Luisa F.; Gonzalez, Liliana A.; Rivera-Perez, Daniela; Rios, Mariana; Berrios, Roslye, V; Vazquez, Yaneisi; Moreno-Tapia, Daniela; Vallejos, Omar P.; Andrade, Catalina A.; Hoppe-Elsholz, Guillermo; Iturriaga, Carolina; Urzua, Marcela; Navarrete, Maria S.; Rojas, Alvaro; Fasce, Rodrigo; Fernandez, Jorge; Mora, Judith; Ramirez, Eugenio; Gaete-Argel, Aracelly; Acevedo, Monica L.; Valiente-Echeverria, Fernando; Soto-Rifo, Ricardo; Weiskopf, Daniela; Grifoni, Alba; Sette, Alessandro; Zeng, Gang; Meng, Weining; Gonzalez-Aramundiz, Jose, V; Johnson, Marina; Goldblatt, David; Gonzalez, Pablo A.; Abarca, Katia; Bueno, Susan M.; Kalergis, Alexis M.Background: The development of vaccines to control the coronavirus disease 2019 (COVID-19) pandemic progression is a worldwide priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. Methods: This study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged & GE;18 years. Volunteers received two doses of CoronaVac separated by 2 (0-14 schedule) or 4 weeks (0-28 schedule); 2302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. Results: Both schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern (VOCs) between schedules. Stimulation of peripheral blood mononuclear cells (PBMCs) with Mega pools of Peptides (MPs) induced the secretion of interferon (IFN)-gamma and the expression of activation induced markers in CD4(+) T cells for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-gamma secretion. Conclusions: Immunization with CoronaVac in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule.
- ItemInterferon β-1a ring prophylaxis to reduce household transmission of SARS-CoV-2: a cluster randomised clinical trial(Elsevier Ltd, 2023) Castro Rodríguez, José Antonio; Fish, Eleanor; Montgomery, Samuel T.; Kollmann, Tobias R.; Iturriaga Ortiz, Carolina Alejandra; Shannon, Casey; Karpievitch, Yuliya; Ho, Joseph; Chen, Virginia; Balshaw, Robert; Ben-Othman, Rym; Aniba, Radhouane; Gidi Yunge, Francisca Andrea; Hartnell, Lucy; Hancock, David G.; Perez Mateluna, Guillermo Andrés; Urzua, Marcela; Tebbutt, Scott J.; Garcia-Huidobro, Munita Diego Nicolas; Perret, Perez Cecilia; Borzutzky Schachter, Arturo José; Stick, Stephen M.© 2023 The Author(s)Background: Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission. Methods: A cluster randomised open label clinical trial was undertaken to determine the effects of pegylated IFNβ-1a administration on SARS-CoV-2 household transmission between December 3rd, 2020 and June 29th, 2021. Index cases were identified from databases of confirmed SARS-CoV-2 individuals in Santiago, Chile. Households were cluster randomised (stratified by household size and age of index cases) to receive 3 doses of 125 μg subcutaneous pegylated IFNβ-1a (172 households, 607 participants), or standard care (169 households, 565 participants). The statistical team was blinded to treatment assignment until the analysis plan was finalised. Analyses were undertaken to determine effects of treatment on viral shedding and viral transmission. Safety analyses included incidence and severity of adverse events in all treatment eligible participants in the standard care arm, or in the treatment arm with at least one dose administered. Clinicaltrials.gov identifier: NCT04552379. Findings: 5154 index cases were assessed for eligibility, 1372 index cases invited to participate, and 341 index cases and their household contacts (n = 831) enrolled. 1172 participants in 341 households underwent randomisation, with 607 assigned to receive IFNβ-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNβ-1a treatment did not affect duration of viral shedding in index cases (absolute risk reduction = −0.2%, 95% CI = −8.46% to 8.06%) and transmission of SARS-CoV-2 to household contacts (absolute risk reduction = 3.87%, 95% CI = −3.6% to 11.3%). Treatment with IFNβ-1a resulted in significantly more treatment-related adverse events, but no increase in overall adverse events or serious adverse events. Interpretation: Based upon the primary analyses, IFNβ-1a treatment did not affect duration of viral shedding or the probability of SARS-CoV-2 transmission to uninfected contacts within a household. Funding: Biogen PTY Ltd. Supply of interferon as ‘Plegridy (peginterferon beta-1a).’ The study was substantially funded by BHP Holdings Pty Ltd.
- ItemMonolayers and Thin Films of Dextran Hydrophobically Modified(SOC BRASILEIRA QUIMICA, 2010) Leiva, Angel; Munoz, Natalia; Urzua, Marcela; Gargallo, Ligia; Radic, DeodatoA series of biodegradable graft copolymers were synthesized by grafting epsilon-caprolactone over dextran of different molecular weights. The obtained copolymers were characterized by Fourier transform infrared spectroscopy FTIR, proton nuclear magnetic resonance H-1 NMR, thermogravimetry and elemental analysis. Stable monolayers at the air-water interface and spin coated thin films were prepared and characterized by the Langmuir technique and by contact angle measurements respectively. The compressibility and static surface elasticity of the monolayers and the surface energy of copolymer thin films show dependence with the epsilon-caprolactone content. From these results it can be concluded that the surface properties of grafted copolymers can be modulated by their composition. Additionally, according to the obtained results, epsilon-caprolactone grafted-dextrans show potential for being used in different applications where surface properties are important.
- ItemNew Hybrid Nanocomposites with Catalytic Properties Obtained by In Situ Preparation of Gold Nanoparticles on Poly (Ionic Liquid)/Poly (4-Vinylpyridine) Nanofibers(2022) Ramirez, Oscar; Leal, Matias; Briones, Ximena; Urzua, Marcela; Bonardd, Sebastian; Saldias, Cesar; Leiva, AngelIn this work, we report the obtaining of new hybrid nanocomposites with catalytic activity formed by nanofibers of polymer blends and gold nanoparticles. The nanofibers were obtained by electrospinning blends of a poly (ionic liquid) (PIL) and its precursor polymer, poly (4-vinyl pyridine) (P4VPy). The characteristics of the nanofibers obtained proved to be dependent on the proportion of polymer in the blends. The nanofibers obtained were used to synthesize, in situ, gold nanoparticles on their surface by two-step procedure. Firstly, the adsorption of precursor ions on the nanofibers and then their reduction with sodium borohydride to generate gold nanoparticles. The results indicated a significant improvement in the performance of PIL-containing nanofibers over pure P4VPy NFs during ion adsorption, reaching a 20% increase in the amount of adsorbed ions and a 6-fold increase in the respective adsorption constant. The catalytic performance of the obtained hybrid systems in the reduction reaction of 4-nitrophenol to 4-aminophenol was studied. Higher catalytic conversions were obtained using the hybrid nanofibers containing PIL and gold nanoparticles achieving a maximum conversion rate of 98%. Remarkably, the highest value of kinetic constant was obtained for the nanofibers with the highest PIL content.
- ItemOn the Versatile Role of Electrospun Polymer Nanofibers as Photocatalytic Hybrid Materials Applied to Contaminated Water Remediation: A Brief Review(2022) Cordoba, Alexander; Saldias, Cesar; Urzua, Marcela; Montalti, Marco; Guernelli, Moreno; Focarete, Maria Letizia; Leiva, AngelA wide variety of materials, strategies, and methods have been proposed to face the challenge of wastewater pollution. The most innovative and promising approaches include the hybrid materials made of polymeric nanofibers and photocatalytic nanoparticles. Electrospun nanofibers with unique properties, such as nanosized diameter, large specific surface area, and high aspect ratio, represent promising materials to support and stabilize photocatalytic nanosized semiconductors. Additionally, the role performed by polymer nanofibers can be extended even further since they can act as an active medium for the in situ synthesis of photocatalytic metal nanoparticles or contribute to pollutant adsorption, facilitating their approach to the photocatalytic sites and their subsequent photodegradation. In this paper, we review the state of the art of electrospun polymer/semiconductor hybrid nanofibers possessing photocatalytic activity and used for the remediation of polluted water by light-driven processes (i.e., based on photocatalytic activity). The crucial role of polymer nanofibers and their versatility in these types of procedures are emphasized.
- ItemQuick and Easy Modification of Glassy Carbon Electrodes with Ionic Liquid and Tetraruthenated Porphyrins for the Electrochemical Determination of Atrazine in Water(2019) Calfuman, Karla; Honores, Jessica; Isaacs, Mauricio; Quezada, Diego; Valdebenito, Javier; Urzua, MarcelaAtrazine is a pesticide used to control broadleaf weeds, however its wide distribution and its high persistence in the soil and in surface waters has resulted in a public and environmental health problem. Present results shows the design, construction and characterization of glassy carbon electrodes modified with tetrarutenated metalloporphyrin (M=Ni (II) and Zn (II)) and 1-butyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide, BMIMNTF2. The modification was reproducible and sensitive for the electrochemical detection of atrazine in neutral media. The detection limit was 230 nM when using GC/BMIMNTF2/ZnTRP and 540 nM with GC/BMIMNTF2/NiTRP, meaning that his methodology can be a feasible and inexpensive way to detect atrazine in trace levels.
- ItemSafety and Non-Inferiority Evaluation of Two Immunization Schedules with an Inactivated SARS-CoV-2 Vaccine in Adults: A Randomized Clinical TrialAbarca Villaseca, Katia; Iturriaga Ortiz, Carolina Alejandra; Urzua, Marcela; Le Corre Perez, Monique Nicole; Pineda Núñez, Augusto Naim; Fernandez Anwandter, Carolina; Domínguez De Landa, María Angelica; González Carbonell, Pablo Andrés; Bueno, Susan M.; Donato, Paulina; Espinoza, Pilar; Fuentes, Daniela; Gonzalez, Marcela; Guzman, Paula; Munoz-Venturelli, Paula; Perez, Carlos M.; Potin, Marcela; Rojas, Alvaro; Gonzalez-Aramundiz, Jose, V; Galvez, Nicolas M. S.; Aguirre-Boza, Francisca; Aljaro, Sofia; Federico Batiz, Luis; Campisto, Yessica; Cepeda, Mariela; Cortes, Aaron; Lopez, Sofia; Loreto Perez, Maria; Schilling, Andrea; Kalergis, Alexis M.Several vaccines have been developed to control the COVID-19 pandemic. CoronaVac (R), 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 (R) 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 (R) is safe, especially in >= 60-year-old participants. Both schedules protected against COVID-19 hospitalization.
- ItemSafety, Tolerability, Bioavailability, and Biological Activity of Inhaled Interferon-& alpha;2b in Healthy Adults: The (INCOVID)-C-2 Phase I Randomized Trial(2023) García-Huidobro Munita, Diego Nicolás; Iturriaga, Carolina; Perez-Mateluna, Guillermo; Fajuri, Paula; Severino Cuevas, Nicolás Felipe; Urzua, Marcela; Fraga, Juan Pablo; Cruz, Javiera de la; Poli, Cecilia; Castro Rodríguez, José Antonio; Fish, Eleanor; Borzutzky, ArturoBackground and ObjectivesInterferons have been identified as a potential treatment alternative for coronavirus disease 2019. This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-& alpha;2b (IFN)-& alpha;2b in healthy adults.MethodsA double-blind, randomized, phase I clinical trial was conducted with two cohorts of healthy subjects aged 18-50 years. The first cohort received 2.5 MIU of inhaled IFN-& alpha;2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-& alpha;2b in a similar scheme (n = 6) or placebo (n = 3). The first two doses were administered in an emergency department, then participants completed their treatment at home. Safety was measured through vital signs, new symptoms, and laboratory tests. Tolerability was measured as participants' treatment acceptability. Bioavailability and biological activity were measured from serum IFN & alpha; concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments.ResultsExposure to inhaled IFN-& alpha;2b at 2.5-MIU or 5-MIU doses did not produce statistically significant changes in participant vital signs, or elicit new symptoms, and standard hematological and biochemical blood measurements were comparable to those recorded in individuals who received placebo. A total of 58 adverse events were observed. All were mild or moderate and did not require medical care. All participants reported very high tolerability towards a twice-daily nebulized treatment for 10 days (98.0, 97.0, and 97.0 in the placebo, 2.5-MIU, and 5-MIU groups, respectively, on a 0- to 100-mm visual analog scale). A dose-dependent mild increase in serum IFN-& alpha; concentrations and an increase in serum RNA expression of IFN-induced genes were observed 11 days after treatment (p < 0.05 for all between-group comparisons).ConclusionsInhaled IFN-& alpha;2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects.
- ItemSpontaneous Adsorption of Gold Nanoparticles by Polyelectrolyte Thin Films(AMER SCIENTIFIC PUBLISHERS, 2012) Urzua, Marcela; Leiva, Angel; Espinoza Beltran, Francisco J.; Briones, Ximena; Saldias, Cesar; Pino, MaximilianoNanocomposed films constituted by gold nanoparticles immobilized onto polyelectrolytes were obtained and studied. To obtain the films, amino terminated silicon wafer surfaces were put in contact with aqueous solution of polyelectrolytes derived from Poly(maleic anhydride-alt-styrene) containing aryl and amine-alkyl groups in the side chains, in this condition the adsorption of macromolecules was achieved. The effects of the chemical nature of the side chains and ionic strength on the amounts of adsorbed polyelectrolytes were studied by ellipsometry. The adsorption of polyelectrolytes increases with increasing ionic strength in agreement with the screening-enhanced adsorption regime; the results are discussed considering the steric hindrance of the side chains and flexibility of the polymers. A spontaneous adsorption process of nanoparticles onto polyelectrolyte films took place when these last were immersed in a gold nanoparticles suspension. The adsorption amounts were qualitatively evaluated by SEM and AFM and these showed to be dependent on chemical structure of polyelectrolytes.