Browsing by Author "Carreño, L.J."

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    An inactivated SARS-CoV-2 vaccine is safe and induces humoral and cellular immunity against virus variants in healthy children and adolescents in Chile
    (2022) Soto, J.A.; Melo-González, F.; Gutierrez-Vera, C.; Schultz, B.M.; Berríos-Rojas, R.V.; Rivera-Pérez, D.; Piña-Iturbe, A.; Hoppe-Elsholz, G.; Duarte, L.F.; Vázquez, Y.; Moreno-Tapia, D.; Ríos, M.; Palacios, P.A.; Garcia-Betancourt, R.; Santibañez, Á.; Mendez, C.; Diethelm-Varela, B.; Astudillo, P.; Calvo, M.; Cárdenas, A.; González, M.; Goldsack, M.; Gutiérrez, V.; Potin, M.; Schilling, A.; Tapia, L.I.; Twele, L.; Villena, R.; Grifoni, A.; Sette, A.; Weiskopf, D.; Fasce, R.A.; Fernández, J.; Mora, J.; Ramírez, E.; Gaete-Argel, A.; Acevedo, M.; Valiente-Echeverría, F.; Soto-Rifo, R.; Retamal-Díaz, A.; Muñoz-Jofré, N.; Meng, X.; Xin, Q.; Alarcón-Bustamante, E.; González-Aramundiz, J.V.; Le Corre, N.; Álvarez, M.J.; González, P.A.; Abarca, K.; Perret, C.; Carreño, L.J.; Kalergis, A.M.; Bueno, S.M.
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    Gestational hypothyroidism increases the severity of experimental autoimmune encephalomyelitis in adult offspring
    (2013) Albornoz, E.A.; Carreño, L.J.; Cortes, C.M.; Gonzalez, P.A.; Cisternas, P.A.; Cautivo, K.M.; Catalán, T.P.; Opazo, M.C.; Eugenin, E.A.; Berman, J.W.; Bueno Ramirez, Susan Marcela; Kalergis, Alexis M.; Riedel, C.A.
    Background: Maternal thyroid hormones play a fundamental role in appropriate fetal development during gestation. Offspring that have been gestated under maternal hypothyroidism suffer cognitive impairment. Thyroid hormone deficiency during gestation can significantly impact the central nervous system by altering the migration, differentiation, and function of neurons, oligodendrocytes, and astrocytes. Given that gestational hypothyroidism alters the immune cell ratio in offspring, it is possible that this condition could result in higher sensitivity for the development of autoimmune diseases. Methods: Adult mice gestated under hypothyroidism were induced with experimental autoimmune encephalomyelitis (EAE). Twenty-one days after EAE induction, the disease score, myelin content, immune cell infiltration, and oligodendrocyte death were evaluated. Results: We observed that mice gestated under hypothyroidism showed higher EAE scores after disease induction during adulthood compared to mice gestated in euthyroidism. In addition, spinal cord sections of mice gestated under hypothyroidism that suffered EAE in adulthood showed higher demyelination, CD4+ and CD8+ infiltration, and increased oligodendrocyte death. Conclusions: These results show for the first time that a deficiency in maternal thyroid hormones during gestation can influence the outcome of a central nervous system inflammatory disease, such as EAE, in their offspring. These data strongly support evaluating thyroid hormones in pregnant women and treating hypothyroidism during pregnancy to prevent increased susceptibility to inflammatory diseases in the central nervous system of offspring. © Copyright 2013, Mary Ann Liebert, Inc. 2013.
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    Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children
    (2022) Soto, J.A.; Melo-González, F.; Gutierrez-Vera, C.; Schultz, B.M.; Berríos-Rojas, R.V.; Rivera-Pérez, D.; Piña-Iturbe, A.; Hoppe-Elsholz, G.; Duarte, L.F.; Vázquez, Y.; Moreno-Tapia, D.; Ríos, M.; Palacios, P.A.; Garcia-Betancourt, R.; Santibañez, Á.; Pacheco, G.A.; Mendez, C.; Andrade, C.A.; Silva, P.H.; Diethelm-Varela, B.; Astudillo, P.; Calvo, M.; Cárdenas, A.; González, M.; Goldsack, M.; Gutiérrez, V.; Potin, M.; Schilling, A.; Tapia, L.I.; Twele, L.; Villena, R.; Grifoni, A.; Sette, A.; Weiskopf, D.; Fasce, R.A.; Fernández, J.; Mora, J.; Ramírez, E.; Gaete-Argel, A.; Acevedo, M.L.; Valiente-Echeverría, F.; Soto-Rifo, R.; Retamal-Díaz, A.; Muñoz-Jofré, N.; Meng, X.; Xin, Q.; Alarcón-Bustamante, E.; González-Aramundiz, J.V.; Le Corre, N.; Álvarez-Figueroa, M.J.; González, P.A.; Abarca, K.; Perret, C.; Carreño, L.J.; Bueno, S.M.; Kalergis, A.M.
    Multiple 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.
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    Modulation of tumor immunity by soluble and membrane-bound molecules at the immunological synapse
    (2013) González, P.A.; Carreño, L.J.; Céspedes, P.F.; Bueno, S.M.; Riedel, C.A.; Kalergis, A.M.
    To circumvent pathology caused by infectious microbes and tumor growth, the host immune system must constantly clear harmful microorganisms and potentially malignant transformed cells. This task is accomplished in part by T-cells, which can directly kill infected or tumorigenic cells. A crucial event determining the recognition and elimination of detrimental cells is antigen recognition by the T cell receptor (TCR) expressed on the surface of T cells. Upon binding of the TCR to cognate peptide-MHC complexes presented on the surface of antigen presenting cells (APCs), a specialized supramolecular structure known as the immunological synapse (IS) assembles at the T cell-APC interface. Such a structure involves massive redistribution of membrane proteins, including TCR/pMHC complexes, modulatory receptor pairs, and adhesion molecules. Furthermore, assembly of the immunological synapse leads to intracellular events that modulate and define the magnitude and characteristics of the T cell response. Here, we discuss recent literature on the regulation and assembly of IS and the mechanisms evolved by tumors to modulate its function to escape T cell cytotoxicity, as well as novel strategies targeting the IS for therapy.