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1. Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection

Author

Anne Schneider, Aurélie Velay, David Rey, Arnaud Fontanet, Timothée Bruel, Baptiste Panaget, Nicolas Meyer, Yves Hansmann, Laurence Kling-Pillitteri, Olivier Schwartz, Floriane Gallais, Samira Fafi-Kremer, Elodie Laugel, Pierre Gantner, María González, Nathalie Reix, Catherine Schmidt-Mutter, Jean-Marc Lessinger, Jérôme De Seze, Ludovic Glady, Marialuisa Partisani, Nicolas Collongues, Morgane Solis, Marie-Josée Wendling, Sophie Bayer, Delphine Planas, Bertram, Marie-Liesse, APPEL À PROJETS GÉNÉRIQUE 2018 - Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées - - HuMABK2018 - ANR-18-CE17-0028 - AAPG2018 - VALID, Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app - - TRANSPLANTEX2011 - ANR-11-LABX-0070 - LABX - VALID, Laboratoire de Virologie [Strasbourg], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Laboratoire de Génétique Moléculaire [CHRU Strasbourg], CHRU Strasbourg, CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Le Trait d'Union, centre de soins de l'infection par le VIH [CHU Strasbourg], Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité), Service des Maladies Infectieuses et Tropicales [CHU Strasbourg], Service de Santé Publique [Strasbourg] (HUS), Les Hôpitaux Universitaires de Strasbourg (HUS), This work was supported by Strasbourg University Hospital (SeroCoV-HUS, PRI 7782), the Agence Nationale de la Recherche (ANR-18-CE17-0028), Laboratoire d'Excellence TRANSPLANTEX (ANR-11-LABX-0070_TRANSPLANTEX), Strasbourg University and Institut National de la Santé et de la Recherche Médicale (UMR_S 1109)., ANR-18-CE17-0028,HuMABK,Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées(2018), ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)

Subjects
Male, Medicine (General), Time Factors, Antibodies, Viral, Neutralization, Immunoglobulin G, 0302 clinical medicine, Medicine, Longitudinal Studies, Prospective Studies, Prospective cohort study, 0303 health sciences, biology, Incidence (epidemiology), Antibody titer, General Medicine, Middle Aged, 3. Good health, Vaccination, Titer, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, Female, Antibody, Research Paper, Adult, COVID-19 Vaccines, Neutralizing antibodies, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, R5-920, Coronavirus Nucleocapsid Proteins, Humans, 030304 developmental biology, business.industry, SARS-CoV-2, Immunity, COVID-19, Phosphoproteins, Antibodies, Neutralizing, Immunity, Humoral, Kinetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Reinfection, Immunology, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

Background Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. Methods This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. Findings A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11–13 of 283 days (95% CI 231–349) for anti-N and 725 days (95% CI 623–921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42–1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. Interpretation Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants., Graphical abstract Image, graphical abstract

Published
2021
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2. Interleukin-6 chemiluminescent immunoassay on Lumipulse G600 II: analytical evaluation and comparison with three other laboratory analyzers

Author

Thomas Lavaux, Ludovic Glady, Jean-Marc Lessinger, Jean-Marc Lacorte, Rim Charchour, CHU Strasbourg, Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), and Sorbonne Université (SU)

Subjects
[SDV]Life Sciences [q-bio], Clinical Biochemistry, Lumipulse, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Chemiluminescent immunoassay, Fujirebio, Medicine, immunoassay, Interleukin 6, assay performances, ComputingMilieux_MISCELLANEOUS, IL-6, Chromatography, biology, medicine.diagnostic_test, business.industry, interleukin-6, Biochemistry (medical), General Medicine, 3. Good health, Method comparison, method comparison, Immunoassay, biology.protein, business, 030217 neurology & neurosurgery
Abstract

International audience

Published
2020
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3. Empagliflozin improved systolic blood pressure, endothelial dysfunction and heart remodeling in the metabolic syndrome ZSF1 rat

Author

A.W. Qureshi, Brigitte Pollet, Valérie B. Schini-Kerth, Hyun-Ho Lee, Djamel Benrahla, Jean-Marc Lessinger, Christophe Bruckert, Muhammad Akmal Farooq, Dominique Stephan, Eric Mayoux, Sin-Hee Park, Sébastien Gaertner, Cyril Auger, Patrick Ohlmann, Olivier Morel, Auger, Cyril, Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Hypertension et Maladies Vasculaires, Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire de Bioimagerie et Pathologies (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire [Strasbourg], Université de Strasbourg (UNISTRA)-Nouvel Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, and Boehringer Ingelheim Pharma GmbH & Co. KG

Subjects
Blood Glucose, lcsh:Diseases of the circulatory (Cardiovascular) system, Endocrinology, Diabetes and Metabolism, Empagliflozin, Blood Pressure, Type 2 diabetes, 030204 cardiovascular system & hematology, SGLT2, Ventricular Function, Left, chemistry.chemical_compound, ZSF1, 0302 clinical medicine, Glucosides, Endothelial dysfunction, Cellular Senescence, Original Investigation, Ventricular Remodeling, Metabolic syndrome, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.anatomical_structure, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cardiology and Cardiovascular Medicine, Artery, medicine.medical_specialty, Systole, Heart structure, 030209 endocrinology & metabolism, Senescence, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Diabetes mellitus, medicine, Animals, Obesity, Benzhydryl Compounds, Sodium-Glucose Transporter 2 Inhibitors, business.industry, Endothelial function, Heart function, medicine.disease, Rats, Zucker, Disease Models, Animal, Endocrinology, Blood pressure, chemistry, lcsh:RC666-701, Heart failure, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Endothelium, Vascular, business, Biomarkers, EMPA
Abstract

BackgroundEmpagliflozin (empa), a selective sodium–glucose cotransporter (SGLT)2 inhibitor, reduced cardiovascular mortality and hospitalization for heart failure in patients with type 2 diabetes at high cardiovascular risk independent of glycemic control. The cardiovascular protective effect of empa was evaluated in an experimental model of metabolic syndrome, the obese ZSF1 rat, and its’ lean control.MethodsLean and obese ZSF1 rats were either non-treated or treated with empa (30 mg/kg/day) for 6 weeks. Vascular reactivity was assessed using mesenteric artery rings, systolic blood pressure by tail-cuff sphygmomanometry, heart function and structural changes by echocardiography, and protein expression levels by Western blot analysis.ResultsEmpa treatment reduced blood glucose levels from 275 to 196 mg/dl in obese ZSF1 rats whereas normoglycemia (134 mg/dl) was present in control lean ZSF1 rats and was unaffected by empa. Obese ZSF1 rats showed increased systolic blood pressure, and blunted endothelium-dependent relaxations associated with the appearance of endothelium-dependent contractile responses (EDCFs) compared to control lean rats. These effects were prevented by the empa treatment. Obese ZSF1 rats showed increased weight of the heart and of the left ventricle volume without the presence of diastolic or systolic dysfunction, which were improved by the empa treatment. An increased expression level of senescence markers (p53, p21, p16), tissue factor, VCAM-1, SGLT1 and SGLT2 and a down-regulation of eNOS were observed in the aortic inner curvature compared to the outer one in the control lean rats, which were prevented by the empa treatment. In the obese ZSF1 rats, no such effects were observed. The empa treatment reduced the increased body weight and weight of lungs, spleen, liver and perirenal fat, hyperglycemia and the increased levels of total cholesterol and triglycerides in obese ZSF1 rats, and increased blood ketone levels and urinary glucose excretion in control lean and obese ZSF1 rats.ConclusionEmpa reduced glucose levels by 28% and improved both endothelial function and cardiac remodeling in the obese ZSF1 rat. Empa also reduced the increased expression level of senescence, and atherothrombotic markers at arterial sites at risk in the control lean, but not obese, ZSF1 rat.

Published
2020
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4. Effects of oxidation on the hydrolysis by cholesterol esterase of sitosteryl esters as compared to a cholesteryl ester

Author

Saïd Ennahar, Dalal Aoude-Werner, Michel Miesch, Francis Raul, Philippe Geoffroy, Diane Julien-David, Jean-Marc Lessinger, Eric Marchioni, and Barthel, Ingrid

Subjects
Swine, Clinical Biochemistry, Biochemistry, Intestinal absorption, chemistry.chemical_compound, Hydrolysis, Endocrinology, Functional food, Stearates, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Organic chemistry, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS, Hypolipidemic Agents, Pharmacology, chemistry.chemical_classification, Chromatography, Cholesterol, Organic Chemistry, Esters, Oxides, Sterol Esterase, Sitosterols, Sterol, Enzyme, chemistry, Low-density lipoprotein, Cholesteryl ester, lipids (amino acids, peptides, and proteins), Cholesterol Esters, Oxidation-Reduction, Oleic Acid
Abstract

Phytosteryl esters (PE) are used as ingredients in functional food to decrease plasma concentration of low density lipoprotein-cholesterol (LDL-C). Effective impairment of cholesterol absorption by PE suggests that these esters are hydrolyzed by the pancreatic cholesterol esterase (CEase, EC 3.1.1.13) and the liberated sterol may interfere with cholesterol reducing its intestinal absorption. PE-enriched foods are marketed for cooking purposes, and temperature is one of the most important factors leading to the formation of oxidation products. Very little is known about the outcome of PE oxides during the digestive process. A new analytical method based on mass spectrometric detection directly after enzymatic reaction was developed to determine in vitro the activity of CEase on PE and their oxides present in functional food. Using this method, we identified a new inhibitor of CEase: sitosteryl 9,10-dihydroxystearate, which behaves as a non-competitive inhibitor of the hydrolysis of cholesteryl oleate and sitosteryl oleate.

Published
2009

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