Browsing by Author "Rios, Mariana"

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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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    ATP-Dependent Biomechanical Properties of Ciliated and Non-Ciliated Cells Measured by Atomic Force Microscopy
    (CELL PRESS, 2016) Droguett, Karla; Navarrete, Camilo; Fuentes, Christian; Rios, Mariana; Villalon, Manuel; Barrera, Nelson
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    Blocking ATP-releasing channels prevents high extracellular ATP levels and airway hyperreactivity in an asthmatic mouse model
    (AMER PHYSIOLOGICAL SOC, 2021) Arzola Martinez, Llilian; Benavente, Rebeca; Vega, Genesis; Rios, Mariana; Fonseca, Wendy; Rasky, Andrew J.; Morris, Susan; Lukacs, Nicholas W.; Villalon, Manuel J.
    Allergic asthma is a chronic airway inflammatory response to different triggers like inhaled allergens. Excessive ATP in fluids from patients with asthma is considered an inflammatory signal and an important autocrine/paracrine modulator of airway physiology. Here, we investigated the deleterious effect of increased extracellular ATP (eATP) concentration on the mucociliary clearance (MCC) effectiveness and determined the role of ATP releasing channels during airway inflammation in an ovalbumin (OVA)-sensitized mouse model. Our allergic mouse model exhibited high levels of eATP measured in the tracheal fluid with a luciferin-luciferase assay and reduced MCC velocity determined by microspheres tracking in the trachea ex vivo. Addition of ATP had a dual effect on MCC, where lower ATP concentration (mu M) increased microspheres velocity, whereas higher concentration (mM) transiently stopped microspheres movement. Also, an augmented ethidium bromide uptake by the allergic tracheal airway epithelium suggests an increase in ATP release channel functionality during inflammatory conditions. The use of carbenoxolone, a nonspecific inhibitor of connexin and pannexini channels reduced the eATP concentration in the allergic mouse tracheal fluid and dye uptake by the airway epithelium, providing evidence that these ATP release channels are facilitating the net flux of ATP to the lumen during airway inflammation. However, only the specific inhibition of pannexinl with (10)Panx peptide significantly reduced eATP in bronchoalveolar lavage and decreased airway hyperresponsiveness in OVA-allergic mouse model. These data provide evidence that blocking eATP may be a pharmacological alternative to be explored in rescue therapy during episodes of airflow restriction in patients with asthma.
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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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    Effect of oestradiol and progesterone on the instant and directional velocity of microsphere movements in the rat oviduct
    (2007) Rios, Mariana; Hermoso, Marcela; Sanchez, Trinidad M.; Croxatto, Horacio B.; Villalon, Manuel J.
    The oviducal transport of eggs to the uterus normally takes 72 - 96 h in the rat, but this is reduced to less than 20 h after a single injection of oestradiol ( E2). This accelerated transport is associated with an increased frequency of pendular movements in the isthmic segment of the oviduct, with increased levels of the gap junction ( GJ) component Connexin ( Cx) 43, and is antagonised by progesterone ( P). In the present study, we investigated the effect of these hormones on the instant and directional velocity of pendular movements and the role of the GJ and its Cx43 component in the kinetic response of the oviduct to E2 and P. Using microspheres as egg surrogates, microsphere instant velocity ( MIV) was measured following treatment with E2, P or P+ E2, which accelerate or delay egg transport. Microspheres were delivered into the oviduct of rats on Day 1 of pregnancy and their movement within the isthmic segment was recorded. Oestrogen increased MIV with faster movement towards the uterus. After P or P+ E2, MIV was similar to that in the control group. Two GJ uncouplers, namely 18 alpha- and 18 beta- glycyrrhetinic acid, blocked the effect of E2 on MIV. Connexin 43 mRNA levels increased over that seen in control with all treatments. In conclusion, the effects of E2 on MIV resulted in faster movements that produced accelerated egg transport towards the uterus. Gap junctions are probably involved as smooth muscle synchronisers in this kinetic effect of E2, but the opposing effects of E2 and P are not exerted at the level of Cx43 transcription.
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    Female offspring gestated in hypothyroxinemia and infected with human Metapneumovirus (hMPV) suffer a more severe infection and have a higher number of activated CD8+ T lymphocytes
    (2022) Funes, Samanta C.; Rios, Mariana; Fernandez-Fierro, Ayleen; Rivera-Perez, Daniela; Soto, Jorge A.; Valbuena, Jose R.; Altamirano-Lagos, Maria J.; Gomez-Santander, Felipe; Jara, Evelyn L.; Zoroquiain, Pablo; Roa, Juan C.; Kalergis, Alexis M.; Riedel, Claudia A.
    Maternal thyroid hormones (THs) are essential for the appropriate development of the fetus and especially for the brain. Recently, some studies have shown that THs deficiency can also alter the immune system development of the progeny and their ability to mount an appropriate response against infectious agents. In this study, we evaluated whether adult mice gestated under hypothyroxinemia (Hpx) showed an altered immune response against infection with human metapneumovirus (hMPV). We observed that female mice gestated under Hpx showed higher clinical scores after seven days of hMPV infection. Besides, males gestated under Hpx have higher lung viral loads at day seven post-infection. Furthermore, the female offspring gestated in Hpx have already reduced the viral load at day seven and accordingly showed an increased proportion of activated (CD71(+) and FasL(+)) CD8(+) T cells in the lungs, which correlated with a trend for a higher histopathological clinical score. These results support that T-4 deficiency during gestation might condition the offspring differently in males and females, enhancing their ability to respond to hMPV.
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    Glycated Albumin Triggers an Inflammatory Response in the Human Airway Epithelium and Causes an Increase in Ciliary Beat Frequency
    (2021) Aitken, Moira L.; Somayaji, Ranjani; Hinds, Thomas R.; Pier, Maricela; Droguett, Karla; Rios, Mariana; Skerrett, Shawn J.; Villalon, Manuel
    The role of inflammation in airway epithelial cells and its regulation are important in several respiratory diseases. When disease is present, the barrier between the pulmonary circulation and the airway epithelium is damaged, allowing serum proteins to enter the airways. We identified that human glycated albumin (GA) is a molecule in human serum that triggers an inflammatory response in human airway epithelial cultures. We observed that single-donor human serum induced IL-8 secretion from primary human airway epithelial cells and from a cystic fibrosis airway cell line (CF1-16) in a dose-dependent manner. IL-8 secretion from airway epithelial cells was time dependent and rapidly increased in the first 4 h of incubation. Stimulation with GA promoted epithelial cells to secrete IL-8, and this increase was blocked by the anti-GA antibody. The IL-8 secretion induced by serum GA was 10-50-fold more potent than TNF alpha or LPS stimulation. GA also has a functional effect on airway epithelial cells in vitro, increasing ciliary beat frequency. Our results demonstrate that the serum molecule GA is pro-inflammatory and triggers host defense responses including increases in IL-8 secretion and ciliary beat frequency in the human airway epithelium. Although the binding site of GA has not yet been described, it is possible that GA could bind to the receptor for advanced glycated end products (RAGE), known to be expressed in the airway epithelium; however, further experiments are needed to identify the mechanism involved. We highlight a possible role for GA in airway inflammation.
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    LPS increase of ciliary beat frequency in respiratory ciliated cells
    (FEDERATION AMER SOC EXP BIOL, 2013) Veronica Carreno, Daniela; Llados, Carmen; Rios, Mariana; Cohen, Noam; Villalon, Manuel