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Start Over Author "Columbia University Medical Center (CUMC)" Publisher elsevier
3 results on '"Columbia University Medical Center (CUMC)"'

1. A model for establishment, maintenance and reactivation of the immune response after vaccination against Ebola virus

Author

Balelli, Irene, Pasin, Chloé, Prague, Mélanie, Crauste, Fabien, Effelterre, Thierry Van, Bockstal, Viki, Solforosi, Laura, Thiébaut, Rodolphe, Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Columbia University Medical Center (CUMC), Columbia University [New York], Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Janssen Pharmaceutica [Beerse], Janssen Vaccines & Prevention [Leiden], This work has received funding from the Innovative Medicines Initiative2 Joint Undertaking under Grant Agreement EBOVAC1 (No. 115854). This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. This work was also supported by the Investissements d’Avenir program managed by the ANR under reference ANR-10-LABX-77., Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), This work has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement EBOVAC1 (N° 115854). This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. This work was also supported by the Investissements d’Avenir program managed by the ANR under reference ANR-10-LABX-77., Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), and Balelli, Irene

Subjects
Mechanistic modeling, Vaccination, [MATH] Mathematics [math], Immunological memory, SISTM, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Heterologous vaccination, Calibration, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, [MATH]Mathematics [math], Sensitivity analysis, Ebola Virus, Identifiability analysis
Abstract

International audience; The 2014-2016 Ebola outbreak in West Africa has triggered accelerated development of several preventive vaccines against Ebola virus. Under the EBOVAC1 consortium, three phase I studies were carried out to assess safety and immunogenicity of a two-dose heterologous vaccination regimen developed by Janssen Vaccines and Prevention in collaboration with Bavarian Nordic. To describe the immune responses induced by the two-dose heterologous vaccine regimen, we propose a mechanistic ODE based model, which takes into account the role of immunological memory. We perform identifiability and sensitivity analysis of the proposed model to establish which kind of biological data are ideally needed in order to accurately estimate parameters, and additionally, which of those are non-identifiable based on the available data. Antibody concentrations data from phase I studies have been used to calibrate the model and show its ability in reproducing the observed antibody dynamics. Together with other factors, the establishment of an effective and reactive immunological memory is of pivotal importance for several prophylactic vaccines. We show that introducing a memory compartment in our calibrated model allows to evaluate the magnitude of the immune response induced by a booster dose and its long-term persistence afterwards.

Published
2020
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2. Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab.

Author

Mehta H, Mashiko S, Angsana J, Rubio M, Hsieh YM, Maari C, Reich K, Blauvelt A, Bissonnette R, Muñoz-Elías EJ, and Sarfati M

Subjects
Adult, Aged, Antibodies, Monoclonal, Humanized therapeutic use, Cell Separation, Female, Flow Cytometry, Humans, Male, Middle Aged, Monocytes immunology, Psoriasis immunology, Psoriasis pathology, Skin cytology, Skin drug effects, Skin immunology, Skin pathology, T-Lymphocyte Subsets immunology, Young Adult, Antibodies, Monoclonal, Humanized pharmacology, Monocytes drug effects, Psoriasis drug therapy, T-Lymphocyte Subsets drug effects
Abstract

Cellular sources of IL-23 and IL-17A driving skin inflammation in psoriasis remain unclear. Using high-dimensional unsupervised flow cytometry analysis, mononuclear phagocytes and T cells were examined in the same lesions of patients before and during guselkumab (IL-23p19 blocker) or secukinumab (IL-17A blocker) treatment. Among CD11c + HLA-DR + mononuclear phagocytes, CD64 bright CD163 - CD14 bright CD1c - CD1a ‒ inflammatory monocyte‒like cells were the predominant IL-23-producing cells and, together with CD64 - CD163 - CD14 - IL-23p19 - TNF-α + inflammatory dendritic cell‒like cells, were increased in lesional compared with those in nonlesional skin taken from the same patient. Within T cells, CD8 + CD49a + and/or CD103 + tissue-resident memory T cells, CD4 + CD25 + FoxP3 + regulatory T cells, and CD4 + CD49a - CD103 - T cells were increased. Moreover, CD4 + CD49a - CD103 - T cells and the relatively rare CD8 + memory T cells equally contributed to IL-17A production. Both treatments decreased the frequencies of inflammatory monocyte‒like, inflammatory dendritic cell‒like, and CD4 + CD49a - CD103 - T cells. In contrast, guselkumab reduced memory T cells while maintaining regulatory T cells and vice versa for secukinumab. Neither drug modified the frequencies of IL-17A + IL ‒ 17F + / - CD4 + or CD8 + T cells. This study reveals the identity of the major IL-23 + mononuclear phagocyte and IL-17 + T-cell subsets in psoriatic skin lesions and paves the way for a better understanding of the mode of action of drugs targeting the IL-23/IL-17A pathway in psoriasis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2021
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3. Child/Adolescent anxiety multimodal study: evaluating safety.

Author

Rynn MA, Walkup JT, Compton SN, Sakolsky DJ, Sherrill JT, Shen S, Kendall PC, McCracken J, Albano AM, Piacentini J, Riddle MA, Keeton C, Waslick B, Chrisman A, Iyengar S, March JS, and Birmaher B

Subjects
Adolescent, Child, Combined Modality Therapy, Diagnostic and Statistical Manual of Mental Disorders, Double-Blind Method, Female, Humans, Logistic Models, Male, Psychiatric Status Rating Scales, Selective Serotonin Reuptake Inhibitors adverse effects, Sertraline adverse effects, Severity of Illness Index, Treatment Outcome, Anxiety, Separation therapy, Cognitive Behavioral Therapy, Phobic Disorders therapy, Selective Serotonin Reuptake Inhibitors therapeutic use, Sertraline therapeutic use
Abstract

Objective: To evaluate the frequency of adverse events (AEs) across 4 treatment conditions in the Child/Adolescent Anxiety Multimodal Study (CAMS), and to compare the frequency of AEs between children and adolescents., Method: Participants ages 7 to 17 years (mean = 10.7 years) meeting the DSM-IV criteria for 1 or more of the following disorders: separation anxiety disorder, generalized anxiety disorder, or social phobia were randomized (2:2:2:1) to cognitive-behavioral therapy (CBT, n = 139), sertraline (SRT, n = 133), a combination of both (COMB, n = 140), or pill placebo (PBO, n = 76). Data on AEs were collected via a standardized inquiry method plus a self-report Physical Symptom Checklist (PSC)., Results: There were no differences between the double-blinded conditions (SRT versus PBO) for total physical and psychiatric AEs or any individual physical or psychiatric AEs. The rates of total physical AEs were greater in the SRT-alone treatment condition when compared to CBT (p < .01) and COMB (p < .01). Moreover, those who received SRT alone reported higher rates of several physical AEs when compared to COMB and CBT. The rate of total psychiatric AEs was higher in children (≤12 years) across all arms (31.7% versus 23.1%, p < .05). Total PSC scores decreased over time, with no significant differences between treatment groups., Conclusion: The results support the tolerability/safety of selective serotonin reuptake inhibitor (SSRI) treatment for anxiety disorders even after adjusting for the number of reporting opportunities, leading to no differences in overall rates of AEs. Few differences occurred on specific items. Additional monitoring of psychiatric AEs is recommended in children (≤12 years). Clinical trial registration information-Child and Adolescent Anxiety Disorders (CAMS); http://clinicaltrials.gov; NCT00052078., (Copyright © 2015 American Academy of Child and Adolescent Psychiatry. All rights reserved.)

Published
2015
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