8 results on '"Marion Gransagne"'
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2. Safety and immunogenicity of a measles-vectored SARS-CoV-2 vaccine candidate, V591 / TMV-083, in healthy adults: results of a randomized, placebo-controlled Phase I study
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Odile Launay, Cécile Artaud, Marie Lachâtre, Mohand Ait-Ahmed, Jelle Klein, Liem Binh Luong Nguyen, Christine Durier, Bastiaan Jansen, Yvonne Tomberger, Nathalie Jolly, Anna Grossmann, Houda Tabbal, Jérémy Brunet, Marion Gransagne, Zaineb Choucha, Damien Batalie, Ana Delgado, Matthias Müllner, Roland Tschismarov, Pieter-Jan Berghmans, Annette Martin, Katrin Ramsauer, Nicolas Escriou, and Christiane Gerke
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SARS-CoV-2 ,COVID-19 ,vaccine ,measles vector ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein. Methods: We performed a randomized, placebo-controlled Phase I trial with an unblinded dose escalation and a double-blind treatment phase at 2 sites in France and Belgium to evaluate the safety and immunogenicity of V591. Ninety healthy SARS-CoV-2 sero-negative adults (18-55 years of age) were randomized into 3 cohorts, each comprising 24 vaccinees and 6 placebo recipients. Participants received two intramuscular injections of a low dose vaccine (1 × 105 median Tissue Culture Infectious Dose [TCID50]), one or two injections of a high dose vaccine (1 × 106 TCID50), or placebo with a 28 day interval. Safety was assessed by solicited and unsolicited adverse events. Immunogenicity was measured by SARS-CoV-2 spike protein-binding antibodies, neutralizing antibodies, spike-specific T cell responses, and anti-measles antibodies. ClinicalTrials.gov, NCT04497298. Findings: Between Aug 10 and Oct 13, 2020, 148 volunteers were screened of whom 90 were randomized. V591 showed a good safety profile at both dose levels. No serious adverse events were reported. At least one treatment-related adverse event was reported by 15 (20.8%) participants receiving V591 vs. 6 (33.3%) of participants receiving placebo. Eighty-one percent of participants receiving two injections of V591 developed spike-binding antibodies after the second injection. However, neutralizing antibodies were detectable on day 56 only in 17% of participants receiving the low dose and 61% receiving the high dose (2 injections). Spike-specific T cell responses were not detected. Pre-existing anti-measles immunity had a statistically significant impact on the immune response to V591, which was in contrast to previous results with the measles vector-based chikungunya vaccine. Interpretation: While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development.
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- 2022
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3. Plasmodium P36 determines host cell receptor usage during sporozoite invasion
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Giulia Manzoni, Carine Marinach, Selma Topçu, Sylvie Briquet, Morgane Grand, Matthieu Tolle, Marion Gransagne, Julien Lescar, Chiara Andolina, Jean-François Franetich, Mirjam B Zeisel, Thierry Huby, Eric Rubinstein, Georges Snounou, Dominique Mazier, François Nosten, Thomas F Baumert, and Olivier Silvie
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malaria ,hepatocyte ,sporozoite ,P. vivax ,P. berghei ,P. yoelii ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Plasmodium sporozoites, the mosquito-transmitted forms of the malaria parasite, first infect the liver for an initial round of replication before the emergence of pathogenic blood stages. Sporozoites represent attractive targets for antimalarial preventive strategies, yet the mechanisms of parasite entry into hepatocytes remain poorly understood. Here we show that the two main species causing malaria in humans, Plasmodium falciparum and Plasmodium vivax, rely on two distinct host cell surface proteins, CD81 and the Scavenger Receptor BI (SR-BI), respectively, to infect hepatocytes. By contrast, CD81 and SR-BI fulfil redundant functions during infection by the rodent parasite P. berghei. Genetic analysis of sporozoite factors reveals the 6-cysteine domain protein P36 as a major parasite determinant of host cell receptor usage. Our data provide molecular insights into the invasion pathways used by different malaria parasites to infect hepatocytes, and establish a functional link between a sporozoite putative ligand and host cell receptors.
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- 2017
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4. Radial spoke protein 9 is necessary for axoneme assembly in Plasmodium but not in trypanosomatid parasites
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Chandra Ramakrishnan, Cécile Fort, Sara Rute Marques, David J. P. Ferguson, Marion Gransagne, Jake Baum, Soraya Chaouch, Elisabeth Mouray, Linda Kohl, Richard J. Wheeler, and Robert E. Sinden
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Cell Biology - Abstract
Flagella are important for eukaryote cell motility, including in sperm, and are vital for life cycle progression of many unicellular eukaryotic pathogens. The “9+2” axoneme in most motile flagella comprises nine outer doublet and two central-pair singlet microtubules. T-shaped radial spokes protrude from the outer doublets towards the central pair and are necessary for effective beating. We asked if there were radial spoke adaptations associated with parasite lineage-specific properties in apicomplexans and trypanosomatids. Following an orthologue search for experimentally uncharacterised radial spoke proteins (RSPs), we identified and analysed RSP9. Trypanosoma brucei and Leishmania mexicana, have an extensive RSP complement including two divergent RSP9 orthologs, necessary for flagellar beating and swimming. Detailed structural analysis showed that neither ortholog is needed for axoneme assembly in Leishmania. In contrast, Plasmodium has a reduced set of RSPs including a single RSP9 ortholog. deletion of which in Plasmodium berghei leads to failure of axoneme formation, failed male gamete release, greatly reduced fertilisation and inefficient life cycle progression in the mosquito. This indicates contrasting selection pressures on axoneme complexity, likely linked with the different mode of assembly of trypanosomatid versus Plasmodium flagella.
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- 2023
5. Prevalence of SARS-CoV-2 antibodies in France: results from nationwide serological surveillance
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Louise Perrin de Facci, Virgile Monnet, Pierre Charneau, Caroline Demeret, Jean-Baptiste Richard, Nicolas Escriou, Daniel Lévy-Bruhl, Gabrielle Jones, Thierry Rose, François Anna, Yvonnick Guillois, Marion Gransagne, Corinne Robin, Sophie Goyard, Stéphane Petres, Stéphane Le Vu, Marie-Noëlle Ungeheuer, Lucie Léon, Laurent Filleul, Sylvie van der Werf, Sibylle Bernard-Stoecklin, Olivier Helynck, Harold Noel, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology, Institut Pasteur [Paris], Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris]-TheraVectys, Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Chimie et Biocatalyse, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Laboratoire CERBA [Saint Ouen l'Aumône], Biomnis Sample Library (BSL), Eurofins Biomnis, Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), We thank Christine Larsen, Bruno Coignard and Jean-Claude Desenclos (Santé publiqueFrance) for their helpful contribution at setting up the study, from Institut Pasteur,Isabelle Cailleau for support in the funding process, Hélène Munier-Lehmann for accessto automate and supply management at the Unit of Chemistry and Biocatalysis, Yves L.Janin for providing the luciferase prosubstrate hikarazine 108, Philippe Souque forproduction of the lentiviral pseudo-types, the whole ICAReB team and COVID-19support staff for sample management at Institut Pasteur, Juliette Paireau (Institut Pas-teur, Santé publique France), Rodolphe Thiébaut (Bordeaux Université) and Xavier deLamballerie (Aix-Marseille Université) for valuable comments onfirst results. We alsothank the team from the Eurofins Biomnis Sample Library and from CerbaHealthcareBenedicte Roquebert (Laboratoire Cerba) and Marie Pierre Guerra (CerbaXpert) forcontributing to sample collection. Santé publique France provided funding to the NRCand to the two centralising biobanks to cover sample collection, preparation, transportand analysis costs. The funder had no role in analysis, interpretation of data or writing ofthe report. S.L.V., G.J. and H.N. had full access to all the data and had responsibility tosubmit for publication., Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-TheraVectys, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Lassailly-Bondaz, Anne, Santé publique France - French National Public Health Agency, Centre National de Référence des virus des infections respiratoires (dont la grippe) [Paris] (CNR), Santé publique France, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
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0301 basic medicine ,Male ,Epidemiology ,[SDV]Life Sciences [q-bio] ,General Physics and Astronomy ,Antibodies, Viral ,Serology ,0302 clinical medicine ,Seroepidemiologic Studies ,Case fatality rate ,Prevalence ,Cumulative incidence ,030212 general & internal medicine ,Child ,Aged, 80 and over ,0303 health sciences ,education.field_of_study ,Multidisciplinary ,biology ,Transmission (medicine) ,Middle Aged ,3. Good health ,[SDV] Life Sciences [q-bio] ,[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology ,Child, Preschool ,Female ,France ,medicine.symptom ,Antibody ,Adult ,medicine.medical_specialty ,Adolescent ,Science ,Population ,Asymptomatic ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Young Adult ,medicine ,Seroprevalence ,Humans ,education ,Epidemics ,030304 developmental biology ,Aged ,business.industry ,SARS-CoV-2 ,Public health ,Infant, Newborn ,COVID-19 ,Infant ,General Chemistry ,030104 developmental biology ,Viral infection ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,biology.protein ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,Demography - Abstract
Assessment of the cumulative incidence of SARS-CoV-2 infections is critical for monitoring the course and extent of the COVID-19 epidemic. Here, we report estimated seroprevalence in the French population and the proportion of infected individuals who developed neutralising antibodies at three points throughout the first epidemic wave. Testing 11,000 residual specimens for anti-SARS-CoV-2 IgG and neutralising antibodies, we find nationwide seroprevalence of 0.41% (95% CI: 0.05–0.88) mid-March, 4.14% (95% CI: 3.31–4.99) mid-April and 4.93% (95% CI: 4.02–5.89) mid-May 2020. Approximately 70% of seropositive individuals have detectable neutralising antibodies. Infection fatality rate is 0.84% (95% CI: 0.70–1.03) and increases exponentially with age. These results confirm that the nationwide lockdown substantially curbed transmission and that the vast majority of the French population remained susceptible to SARS-CoV-2 in May 2020. Our study shows the progression of the first epidemic wave and provides a framework to inform the ongoing public health response as viral transmission continues globally., The percentage of national populations infected during the first stages of the COVID-19 pandemic are unclear owing to limited early testing. Here the authors provide a nation-wide prevalence study of SARS-CoV-2 antibodies in France from the first wave of COVID-19 in 2020, including stratification based on age, sex and region.
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- 2021
6. High seroprevalence but short‐lived immune response to SARS‐CoV‐2 infection in Paris
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Pierre Charneau, Philippe Souque, Evelyne Dufour, Marion Gransagne, Stéphane Petres, Ana Ines Lalanne, Thierry Rose, Isabelle Turbiez, François Dejardin, François Anna, Odile Richard-Le Goff, Olivier Helynck, Maude Guillot-Delost, Sophie Goyard, Alexia Savignoni, François-Clément Bidard, Zaineb Choucha, Fabien Nevo, Franck Perez, Delphine Louis, Véronique Gillon, Yves L. Janin, A Gobillion, Nicolas Escriou, Olivier Lantz, Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris]-TheraVectys, Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Curie [Paris], Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology, Institut Pasteur [Paris], Laboratoire d’innovation : vaccins – Innovation lab : vaccines, Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Plateforme technologique Production et purification de protéines recombinantes – Production and Purification of Recombinant Proteins Technological Platform (PPR), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Chimie et Biocatalyse, This work was made possible thanks to the financial support obtained through the URGENCE nouveau coronavirus fundraising campaign of Institut Pasteur and the financial support of the Fondation Total. This study was funded in part by a grant from Fondation de France and by Institut Curie Institutional funding. The luciferin synthesis development has been supported by DARRI (ValoExpress 2016-2018). LuLISA development has been supported by IARP Pasteur-Carnot MI (2019-2020)., Institut Pasteur [Paris] (IP)-TheraVectys, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Université Paris-Saclay, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Lassailly-Bondaz, Anne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
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0301 basic medicine ,Male ,Time Factors ,Antibodies, Viral ,SARS‐CoV‐2 ,MESH: Antibodies, Neutralizing ,Serology ,0302 clinical medicine ,Seroepidemiologic Studies ,Epidemiology ,MESH: COVID-19 ,Immunology and Allergy ,030212 general & internal medicine ,Research Articles ,MESH: Immunoglobulin G ,0303 health sciences ,education.field_of_study ,MESH: Paris ,3. Good health ,Titer ,Research Article|Basic ,ELISA ,Female ,medicine.symptom ,Bioluminescence ,Adult ,MESH: Pandemics ,medicine.medical_specialty ,Paris ,Population ,Immunology ,Anosmia ,Immunity to infection ,Biology ,Asymptomatic ,Virus ,03 medical and health sciences ,COVID‐19 ,Internal medicine ,medicine ,Humans ,Basic ,education ,Pandemics ,030304 developmental biology ,LuLISA ,MESH: Seroepidemiologic Studies ,MESH: Humans ,SARS-CoV-2 ,business.industry ,MESH: Time Factors ,COVID-19 ,MESH: Adult ,Ageusia ,Antibodies, Neutralizing ,MESH: Male ,030104 developmental biology ,Immunization ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Immunoglobulin G ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,MESH: Female ,MESH: Antibodies, Viral ,030215 immunology - Abstract
International audience; Background Although the COVID-19 pandemic peaked in March/April 2020 in France, the prevalence of infection is barely known. Herein, we assessed the serological response against the SARS-CoV-2 virus in a large population working in one institution of the Paris conurbation. We set up two high-throughput and sensitive methods to assess SARS CoV-2 Nucleoprotein and Spike protein-specific IgG response along with a pseudo-neutralization assay in sera. We studied 1847 participants who also answered a web-based survey on clinical symptoms.Methods and Results In May-July 2020, 11% (95% CI: 9.7-12.6) of serums were positive for IgG against the SARS-CoV-2 N and S protein and 9.5% (CI:8.2-11.0) were pseudo-neutralizer. The prevalence of immunization was 11.6% (CI:10.2-13.2) considering positivity in at least one assays. In 5% (CI:3.9-7.1) of RT-qPCR positive individuals, no systemic IgGs were detected. Among immune individuals, 21% had been asymptomatic.Anosmia and ageusia occurred in 52% of the IgG-positive individuals and in 3% of the negative ones. In contrast, 30% of the anosmia-ageusia cases were seronegative suggesting that the true prevalence of infection may reach 16.6%. In sera obtained 4-8 weeks after the first sampling anti-N and anti-S IgG titers and pseudo-neutralization activity declined by 31%, 17% and 53%, respectively with half-life of 35, 87 and 28 days, respectively.Conclusions The population studied being not particularly exposed to SARS-CoV-2 infection is representative of active workers in the Paris conurbation, suggesting that the current epidemiological models may underestimate the true prevalence of infection. The short lifespan of the serological systemic responses hinders retrospective assessment of the epidemic extent.
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- 2020
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7. SARS-CoV-2 serological analysis of COVID-19 hospitalized patients, pauci-symptomatic individuals and blood donors
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Lucie Le Fevre, Diane Descamps, Sylvie van der Werf, Nicolas Escriou, Delphine Planas, Olivier Schwartz, Flora Donati, Cyril Planchais, Rémy Robinot, Isabelle Staropoli, Bernadette Crescenzo, Bruno Hoen, Mireille Nowakowski, Marion Gransagne, Mélanie Albert, Jérémy Dufloo, Marc Eloit, Stéphane Petres, Camille Besombes, Ludivine Grzelak, Yazdan Yazdanpanah, Hugo Mouquet, Sarah Temmam, Arnaud Fontanet, Pierre Charneau, Marija Backovic, Vincent Enouf, Pascal Morel, Françoise Porrot, Quentin Le Hingrat, Audrey Lemaitre, Timothée Bruel, Philippe Souque, Maxime Chazal, Guillaume Mellon, Laura Tondeur, Anabelle Pourbaix, Simon Rolland, Félix A. Rey, Christèle Huon, Julian Buchrieser, Sylvie Behillil, Marie-Noëlle Ungeheuer, François Anna, Maaran Michael Rajah, Lila Bouadma, Florence Guivel, Jacques Bellalou, Marie-Aude Creach, Caroline Demeret, and Kuang-Yu Chen
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0303 health sciences ,education.field_of_study ,biology ,030306 microbiology ,business.industry ,Population ,Antibody titer ,Virology ,Asymptomatic ,3. Good health ,Serology ,03 medical and health sciences ,Antigen ,biology.protein ,Medicine ,Seroprevalence ,Antibody ,Seroconversion ,medicine.symptom ,education ,business ,030304 developmental biology - Abstract
It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their antibody response profile. Here, we performed a pilot study to assess the levels of anti-SARS-CoV-2 antibodies in samples taken from 491 pre-epidemic individuals, 51 patients from Hôpital Bichat (Paris), 209 pauci-symptomatic individuals in the French Oise region and 200 contemporary Oise blood donors. Two in-house ELISA assays, that recognize the full-length nucleoprotein (N) or trimeric Spike (S) ectodomain were implemented. We also developed two novel assays: the S-Flow assay, which is based on the recognition of S at the cell surface by flow-cytometry, and the LIPS assay that recognizes diverse antigens (including S1 or N C-terminal domain) by immunoprecipitation. Overall, the results obtained with the four assays were similar, with differences in sensitivity that can be attributed to the technique and the antigen in use. High antibody titers were associated with neutralisation activity, assessed using infectious SARS-CoV-2 or lentiviral-S pseudotypes. In hospitalized patients, seroconversion and neutralisation occurred on 5-14 days post symptom onset, confirming previous studies. Seropositivity was detected in 29% of pauci-symptomatic individuals within 15 days post-symptoms and 3 % of blood of healthy donors collected in the area of a cluster of COVID cases. Altogether, our assays allow for a broad evaluation of SARS-CoV2 seroprevalence and antibody profiling in different population subsets.
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- 2020
8. Author response: Plasmodium P36 determines host cell receptor usage during sporozoite invasion
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Marion Gransagne, Thomas F. Baumert, Sylvie Briquet, Thierry Huby, Olivier Silvie, Morgane Grand, Eric Rubinstein, François Nosten, Matthieu Tolle, Chiara Andolina, Giulia Manzoni, Dominique Mazier, Selma Topçu, Mirjam B. Zeisel, Julien Lescar, Jean-François Franetich, Carine Marinach, and Georges Snounou
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biology ,biology.organism_classification ,Receptor ,Plasmodium ,Virology - Published
- 2017
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