Browsing by Author "Iturriaga, Carolina"

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    A 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.
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    A cluster randomized trial of interferon ß-1a for the reduction of transmission of SARS-Cov-2: protocol for the Containing Coronavirus Disease 19 trial (ConCorD-19)
    (2021) Iturriaga, Carolina; Eiffler, Nat; Aniba, Rad; Pérez Mateluna, Guillermo; Meyer, Jessica K. V.; Severino Cuevas, Nicolás Felipe; Borzutzky Schachter, Arturo; Perret Pérez, Cecilia; Castro Rodríguez, José Antonio; García-Huidobro Munita, Diego Nicolás; Iturriaga, Carolina; Eiffler, Nat; Aniba, Rad; Pérez Mateluna, Guillermo; Meyer, Jessica K. V.; Severino Cuevas, Nicolás Felipe; Borzutzky Schachter, Arturo; Perret Pérez, Cecilia; Castro Rodríguez, José Antonio; García-Huidobro Munita, Diego Nicolás; Iturriaga, Carolina; Eiffler, Nat; Aniba, Rad; Pérez Mateluna, Guillermo; Meyer, Jessica K. V.; Severino Cuevas, Nicolás Felipe; Borzutzky Schachter, Arturo; Perret Pérez, Cecilia; Castro Rodríguez, José Antonio; García-Huidobro Munita, Diego Nicolás; Iturriaga, Carolina; Eiffler, Nat; Aniba, Rad; Pérez Mateluna, Guillermo; Meyer, Jessica K. V.; Severino Cuevas, Nicolás Felipe; Borzutzky Schachter, Arturo; Perret Pérez, Cecilia; Castro Rodríguez, José Antonio; García-Huidobro Munita, Diego Nicolás
    Abstract Background SARS-CoV-2 infection rapidly spreads in populations due to the high rates of community transmission. Interrupting the shedding of SARS-CoV-2 may reduce the incidence of Coronavirus Disease 19 (COVID-19). Herein we provide a protocol for a cluster randomized trial that will examine the effectiveness of treatment with interferon (IFN) ß-1a compared to standard of care in limiting the transmission of SARS-CoV-2. Co-primary objectives are to determine whether IFN therapy reduces (a) the proportion of infected cases shedding SARS-CoV-2 at day 11 post randomization and (b) the incidence of transmission of SARS-CoV-2 infection from index cases to treatment-eligible household post-exposure contacts at day 11 after randomization. Secondary objectives include assessing the impact of IFN treatment on duration of viral clearance, hospitalizations and fatalities, and evaluating the safety of IFN treatment. Methods Three hundred and ten households, each including an index case with a recent COVID-19 diagnosis and at least one asymptomatic treatment-eligible household contact, will be randomized to receive 3 doses of 125 μg IFN ß-1a by subcutaneous administration (days 1, 6, and 11), or standard of care. All participants will be followed until day 29. Discussion The results from this trial will identify whether IFN ß treatment of mild or moderate COVID-19 cases accelerates viral clearance and prevents disease progression and whether IFN ß treatment of post-exposure contacts of COVID-19 cases reduces transmission of infection. Trial Registration: This trial is registered at ClinicalTrials.gov NCT04552379; date of registration September 17, 2020.
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    Association between obesity and atopic dermatitis in children: A case-control study in a high obesity prevalence population
    (2022) Iturriaga, Carolina; Bustos, María Francisca; Le Roy, Catalina; Rodríguez, Rocío; Cifuentes, Lorena; Silva-Valenzuela, Sergio; Vera-Kellet, Cristián; Cristi, Francisca; Pérez-Mateluna, Guillermo; Cabalín, Carolina; Hoyos-Bachiloglu, Rodrigo; Camargo Jr., Carlos A.; Borzutzky Schachter, Arturo
    Background/Objective: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Research suggests an association between obesity and AD, although evidence is lacking from Latin American populations. This study evaluated the association of obesity with AD in children from Chile, a country with high obesity prevalence. Methods: A case-control study was performed in children with active AD (cases) and healthy controls (HCs) from Santiago, Chile. Body mass index was evaluated by z-score (z-BMI), with overweight defined as z-BMI ≥+1 and <+2, and obesity as z-BMI ≥+2. Abdominal obesity was defined by a waist circumference-to-height ratio (WHR) ≥0.5. AD severity was evaluated by Scoring AD (SCORAD) index. Results: A total of 174 children with AD and 101 controls were included. AD patients had similar overweight (27% vs. 28%) and obesity (21% vs. 26%) rates as HCs (p = .65). Abdominal obesity rates were also comparable (64% vs. 62%, p = .81). In sex-specific analyses, girls with AD had higher abdominal obesity rates than HCs (71% vs. 53%, p < .05) while boys with AD had lower abdominal obesity rates than HCs (53% vs. 75%, p = .03). Among children with AD, higher z-BMI or WHR did not correlate with higher SCORAD, eosinophil counts or total IgE. Conclusion: In our study, Chilean children with AD had high but similar rates of obesity as HCs, but showed sex-specific associations of abdominal obesity and AD. Further research is needed to evaluate these associations and the roles that weight excess and weight loss could play in the pathogenesis and treatment of AD.
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    Differences 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.
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    Differential immune response induced by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial
    (2022) Galvez Arriagada, Nicolás Marcelo Salvador; Pacheco Ruidiaz, Gaspar Andrés; Schültz Lombardic, Barbara Melinka; Melo González, Felipe Andrés; Soto Ramírez, Jorge Andrés; Duarte Peñaloza, Luisa Fernanda; González Carreño, Liliana Andrea; Rivera Pérez, Daniela Belén; Ríos Raggio, Mariana; Berríos, Roslye V.; Vazquéz Hernandéz, Yaneisi; Moreno Tapia, Daniela Paz; Vallejos Galvez, Omar Patricio; Andrade Parra, Catalina Andrea; Hoppe Elsholz, Guillermo; Iturriaga, Carolina; Urzua, Marcela; Navarrete, María S.; Rojas González, Álvaro Miguel; Fasce Pineda, Rodrigo Andrés; Fernández, Jorge; Mora, Judith; Ramírez, Eugenio; Gaete Argel, Aracelly; Acevedo Blanco, Mónica Andrea; Valiente Echeverría, Fernando; Soto Rifo, Ricardo; Weiskopf, Daniela; Grifoni, Alba; Sette, Alessandro; Zeng, Gang; Meng, Weining; González Aramundiz, José Vicente; Goldblatt, David; Acuna González, Pablo Ernesto; Abarca Villaseca, Katia; Bueno Ramírez, Susan Marcela; Kalergis Parra, Alexis Mikes
    Background: The development of vaccines to control the COVID-19 pandemic progression is a worldwide priority. CoronaVac® is an inactivated 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 ≥18 years. Volunteers received two doses of CoronaVac® separated by two (0-14 schedule) or four weeks (0-28 schedule). 2,302 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 between schedules. Stimulation of PBMCs with MPs induced the secretion of IFN-γ and the expression of activation induced markers for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-γ 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.
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    Early origins of allergy and asthma (ARIES): study protocol for a prospective prenatal birth cohort in Chile.
    (2020) Hernández Vargas, Caroll Daffner; Casanello Toledo, Paola Cecilia; Harris D., Paul R.; Castro Rodríguez, José Antonio; Iturriaga, Carolina; Pérez Mateluna, Guillermo; Farías Jofré, Marcelo Enrique; Urzúa, Marcela; Hernández Carreño, Cherie Francisca; Serrano Honeyman, Carolina; Hernández Vargas, Caroll Daffner; Casanello Toledo, Paola Cecilia; Harris D., Paul R.; Castro Rodríguez, José Antonio; Iturriaga, Carolina; Pérez Mateluna, Guillermo; Farías Jofré, Marcelo Enrique; Urzúa, Marcela; Hernández Carreño, Cherie Francisca; Serrano Honeyman, Carolina
    Abstract Background Growing evidence shows that atopic dermatitis (AD), food allergy (FA), allergic rhinitis, and asthma are largely determined during the first 1000 days (time elapsed from conception to the 2nd birthday). The ARIES birth cohort aims to determine prenatal and perinatal conditions, as well as genetic and epigenetic factors, that participate in the early setting of immune responses, and the role of these in the later determination of the risk of allergic diseases and asthma in the offspring. Methods We have designed a birth cohort of 250 families with prenatal recruitment (~ 14 weeks). We will genotype relevant allergy/asthma-associated variants in trios and will perform immunophenotyping and evaluation of allergy biomarkers in cord blood. At 1 and 2 years of age we will assess if infants have developed allergic sensitization, AD, FA, as well as biomarkers of asthma including the asthma predictive index. We will also evaluate how maternal conditions modify immune programming through epigenetic modifications and will then depict newborn epigenetic cues of allergy/asthma risk. Next, we will assess composition/diversity of maternal gut, placenta, breastmilk and infant gut microbiome and their association with immunophenotype and biomarkers at birth, and clinical outcomes at age 1 and 2. Finally, we plan to assess how environmental exposures (perinatal outdoor and indoor pollution, allergens and endotoxin) affect the incidence of allergic sensitization, AD, FA, and risk of asthma. Discussion The in-depth study of the ARIES birth cohort shall provide crucial information to understand the rising incidence of allergies and asthma in developing countries, and hopefully provide cues on how to prevent and treat these diseases. Trial registration clinicaltrials.gov NCT04186949, retrospectively registered on December 5, 2019.
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    Estudio de validez diagnóstica de la prueba de hemorragia oculta fecal en lactantes con proctocolitis alérgica inducida por proteína alimentaria
    (2018) Concha, Sara; Cabalín, Carolina; Iturriaga, Carolina; Pérez Mateluna, Guillermo; Gómez, Constanza; Cifuentes, Lorena; Harris D., Paul R.; Gana Ansaldo, Juan Cristóbal; Borzutzky Schachter, Arturo
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    Hertoghe’s sign in atopic dermatitis
    (2020) Borzutzky Schachter, Arturo; Tejos-Bravo, Macarena; Venegas, Luis F.; Iturriaga, Carolina
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    High prevalence of lupin allergy among patients with peanut allergy: identification of γ-conglutin as majo allergen
    (American College of Allergy, Asthma and Immunology, 2022) Aguilera-Insunza, Raquel; Iturriaga, Carolina; Mariñanco, Angélica; Venegas, Luis; Aravena, Gabriela; Pérez-Mateluna, Guillermo; Baptista-Dias, Nathalia; Borzutzky Schachter, Arturo; Wandersleben, Traudy
    Background: Lupin is a protein-rich legume with a growing presence in the food market worldwide. With increased consumption, lupin allergy (LA) reports are also rising. Uncertainties exist on the cross-reactivity between peanut and lupin, the allergenic potential of different lupin species, and sensitization patterns among different populations. Objective: To evaluate the molecular basis of LA and to determine lupin allergens from 3 different species that may be involved in peanut allergy (PA) cross-reactivity. Methods: A total of 43 subjects with PA, those with LA, or controls without food allergy were evaluated with skin prick tests (SPTs) and specific IgEs (sIgEs). Lupin-sensitized subjects were offered a lupin oral food challenge (OFC). Immunoblots and enzyme-linked immunosorbent assays were performed on sera from lupin-sensitized subjects. Results: In this study, 44% of the PA subjects were confirmed to have LA by OFC. Anaphylaxis was the most frequent manifestation after lupin consumption, with a minimal eliciting dosage of 1 g lupin flour. There was no difference in lupin sIgE or SPT wheal size between lupin-sensitized and confirmed LA subjects or in the severity of symptoms among confirmed LA subjects. Sera from lupin-sensitized subjects uniformly reacted to all 3 different lupin species. Immunoblotting and enzyme-linked immunosorbent assays revealed immunoglobulin E binding to a- and g-conglutin in all analyzed sera, whereas a- and b-conglutin recognition was variable. Conclusion: Our findings reveal a high prevalence of LA among PA subjects, emphasizing lupin must be labeled as an allergen in foods. Owing to high variability in lupin-sIgE and lupin-SPT results, LA diagnosis may require OFC. In our population, g-conglutin is the major allergen of lupin
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    Interim report: Safety and immunogenicity of an inactivated vaccine against SARS-CoV-2 in healthy chilean adults in a phase 3 clinical trial
    (2021) Bueno Ramírez, Susan; Abarca Villaseca, Katia; González Adonis, Pablo Andrés; Gálvez Arriagada, Nicolás Marcelo Salvador; Soto Ramírez, Jorge Andrés; Duarte Peñaloza, Luisa Fernanda; Schultz Lombardic, Bárbara M.; Pacheco, Gaspar A.; González Carreño, Liliana Andrea; Vázquez, Yaneisi; Ríos Raggio, Mariana; Melo González, Felipe; Rivera Pérez, Daniela; Iturriaga, Carolina; Urzúa Acevedo, Marcela del Pilar; Domínguez De Landa, María Angélica; Andrade Parra, Catalina Andrea; Berríos Rojas, Roslye; Canedo Marroquín, Giselda; Covián, Camila
    The ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile.
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    Oral vitamin D modulates the epidermal expression of the vitamin D receptor and cathelicidin in children with atopic dermatitis
    (2022) Cabalín, Carolina; Pérez-Mateluna, Guillermo; Iturriaga, Carolina; Camargo Jr., Carlos A.; Borzutzky Schachter, Arturo
    Although vitamin D (VD) is known to have multiple effects on the skin and immunity, its effects on atopic dermatitis (AD) severity remain unclear. We investigated whether oral cholecalciferol (VD3) supplementation changes stratum corneum expression of the vitamin D receptor (vdr), and the epidermal alarmins Cathelicidin Antimicrobial Peptide (camp/LL-37) and Thymic Stromal Lymphopoietin (tslp) in children with AD. We conducted an open-label supplementation study with weekly oral VD3 for six weeks in children with AD. Serum 25-hydroxyvitamin D (25OHD), lesional Staphylococcus aureus colonization, and AD severity evaluated by SCORAD index were evaluated before and after supplementation. Tape stripping (TS) was performed on non-lesional and lesional skin to measure mRNA expression of vdr, camp, and tslp through RT-qPCR and LL-37 peptide by ELISA. Twenty-two children with moderate–severe AD received weekly oral VD3 for six weeks. Total serum 25OHD increased from 45.1 ± 23 to 93.5 ± 24.3 nmoL/L (p < 0.0001), while SCORAD decreased from 41.4 ± 13.5 to 31.5 ± 15.8 (p < 0.0001). After treatment, epidermal gene expression of camp increased significantly in non-lesional (p = 0.014) and lesional (p = 0.0007) tape stripping samples, while vdr only increased in lesional skin samples (p < 0.0001). LL-37 peptide increased significantly only in lesional skin samples (p = 0.008). Gene expression of tslp did not change after oral VD3 treatment. In children with AD, oral VD3 supplementation was associated with improved VD status and AD severity, as well as increased VDR and Cathelicidin expression in lesional skin, which provide mechanistic clues on its effects.
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    Potenciales consecuencias neurocognitivas de infección por virus respiratorio sincicial humano
    (2016) Flores, Juan Carlos; Bohmwald Prieto, Karen; Espinoza Véliz, Janyra Alejandra; Jara, Cristina; Peña, Marcela; Hoyos Bachiloglu, Rodrigo Andrés; Iturriaga, Carolina; Kalergis Parra, Alexis Mikes; Borzutzky Schachter, Arturo
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    Safety, 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, Arturo
    Background 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.
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    Vitamin D status and supplementation in Antarctica: a systematic review and meta- analysis
    (2021) Cabalin, Carolina; Iturriaga, Carolina; Perez Mateluna, Guillermo; Echeverria, Denise; Camargo Jr, Carlos A.; Borzutzky Schachter, Arturo
    Living at high latitudes is associated with vitamin D (VD) deficiency. An ideal setting to study this is the Antarctic continent, which has temporary inhabitants, but the magnitude of the effect of living in Antarctica and the effects of VD supplementation on this population remain unclear. We performed a systematic review and meta-analysis to assess the effect of temporary residence in Antarctica and impact of VD supplementation on VD status of this population. Random-effects meta-analyses were performed to assess serum 25-hydroxyvitamin D (25(OH)D) concentration changes after Antarctic residence (13 studies, 294 subjects) and after VD supplementation (5 studies, 213 subjects). Serum 25(OH)D mean difference after temporary residence in Antarctica was -15.0 nmol/L (95%CI: -25.9, -4.2; I-2=92%). Subgroup meta-analyses of studies evaluating Antarctic summer and winter stays showed 25(OH)D only decreases when overwintering (winter 25(OH)D change -17.0 nmol/L [95%CI: -24.1, -9.8; I-2=83%] vs. summer 25(OH)D change 1.3 nmol/L [95%CI: -14.6, 17.1; I-2=86%]). The meta-analysis of VD supplementation studies in Antarctica showed a mean 25(OH)D increase after supplementation of 10.8 nmol/L (95%CI: 3.3, 18.3; I-2=88%). In conclusion, VD status significantly worsens after inhabiting Antarctica, particularly when over-wintering. VD supplementation can prevent worsening of VD status and should be considered in this population.
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    Weekly Vitamin D Supplementation to Prevent Acute Respiratory Infections in Young Children at Different Latitudes: A Randomized Controlled Trial
    (2024) Reyes, Maria Loreto; Vizcaya, Cecilia; Le Roy, Catalina; Loureiro, Carolina; Brinkmann, Karin; Campos, Laura; Arancibia, Monica; Iturriaga, Carolina; Perez-Mateluna, Guillermo; Rojas-McKenzie, Maite; Dominguez, Gonzalo; Camargo Jr, Carlos A.; Borzutzky, Arturo
    Objective: To evaluate the effectiveness of weekly vitamin D supplementation in reducing the number of acute respiratory infections (ARI) in preschool children. Study design: Randomized, double-blind, placebo-controlled trial in 303 children aged 1.5-3.5 years from 2014 to 2105 in 3 Chilean cities at different latitudes: Santiago (33 degrees S, n = 101), Talcahuano (37 degrees S, n = 103), and Punta Arenas (53 degrees S, n = 99). Participants were allocated (1:1:1) to receive placebo, cholecalciferol (vitamin D3 (VD3)) 5600 IU/week (low-dose), or 11 200 IU/week (high-dose) for 6 months. Primary outcome was parent-reported number of ARI; secondary outcomes included number of ARI hospitalizations, change of serum 25-hydroxyvitamin D (25(OH)D) and LL-37/cathelicidin levels, and adverse events. Results: The mean age of participants was 26 +/- 6 months; 45% were female. Baseline 25(OH)D was 24.9 +/- 6.1 ng/ml, with 23% having 25(OH)D <20 ng/ml. No significant baseline clinical or laboratory differences were observed among groups. Overall, 64% (n = 194) completed study participation, without baseline differences between subjects lost to follow-up vs those completing participation or differences in completion rates across groups. After 6 months, a dose-dependent increase in serum 25(OH)D was observed from the VD3 intervention (P < .001), with a higher proportion of subjects ending the trial with 25(OH)D <20 ng/ml in the placebo group (30.8%) vs the low-dose (7.4%) and high-dose groups (5.1%). However, no group differences were observed in number of ARI (P = .85), ARI hospitalizations (P = .20), LL-37/cathelicidin change (P = .30), or adverse events (P = .41). Conclusions: While weekly VD3 supplementation, in doses equivalent to 800 IU and 1600 IU daily, was associated with improved 25(OH)D levels in preschoolers, we did not find a reduced number of ARI in this sample.