6 results on '"Laura Barrot"'
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2. Assessment of irradiated socket healing in the rabbit's mandible: Experimental study
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Aline, Desoutter, Laura, Barrot, Stephan, Langonnet, Jean-Christophe, Béra, and Anne-Gaëlle, Chaux
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- 2020
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3. Ribavirin does not potentiate favipiravir antiviral activity against Ebola virus in non-human primates
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Vincent Madelain, Aurélie Duthey, France Mentré, Frédéric Jacquot, Caroline Solas, Bruno Lacarelle, Audrey Vallvé, Stéphane Barron, Laura Barrot, Stéphanie Mundweiler, Damien Thomas, Caroline Carbonnelle, Hervé Raoul, Xavier de Lamballerie, and Jérémie Guedj
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0301 basic medicine ,Anemia ,viruses ,030106 microbiology ,Favipiravir ,medicine.disease_cause ,Virus Replication ,Antiviral Agents ,03 medical and health sciences ,chemistry.chemical_compound ,Virology ,Ribavirin ,medicine ,Animals ,Lassa fever ,Survival rate ,Pharmacology ,Ebola virus ,business.industry ,virus diseases ,Hemorrhagic Fever, Ebola ,Viral Load ,medicine.disease ,Ebolavirus ,Amides ,Disease Models, Animal ,Macaca fascicularis ,030104 developmental biology ,chemistry ,Viral replication ,Pyrazines ,Female ,business ,Viral load - Abstract
Background In spite of recurrent and dramatic outbreaks, there are no therapeutics approved against Ebola virus disease. Favipiravir, a RNA polymerase inhibitor active against several RNA viruses, recently demonstrated significant but not complete protection in a non-human primate model of Ebola virus disease. In this study, we assessed the benefit of the combination of favipiravir and ribavirin, another broad spectrum antiviral agent, in the same model. Methods 15 female cynomolgus macaques were challenged intramuscularly with 1,000 FFU of Ebola virus Gabon 2001 strain and followed for 21 days. All animals received favipiravir 180 mg/kg twice a day (BID), either as monotherapy (n = 5) or in combination with ribavirin (n = 10). Ribavirin was given either at the dose 10 mg/kg BID (n = 5) or 5 mg/kg BID (n = 5). Favipiravir and ribavirin were initiated two and one days before viral challenge respectively and treatment were continued for 14 days. Treatment effects on viral and hematological markers were assessed using a mathematical model. Survival rate of 0% and 20% were obtained in macaques receiving favipiravir plus ribavirin 10 and 5 mg/kg BID, respectively, compared to 40% in the favipiravir monotherapy group (P = 0.061 when comparing monotherapy and bitherapy, log rank). Viral dynamic modeling analysis did not identify an association between plasma concentrations of ribavirin and viral load levels. Using a model of erythropoiesis, plasma concentrations of ribavirin were strongly associated with a hemoglobin drop (p = 0.0015). Conclusion Ribavirin plus favipiravir did not extend survival rates and did not lower viral replication rate compared to favipiravir monotherapy in this animal model. Patients receiving this combination in other indications, such as Lassa fever, should be closely monitored to prevent potential toxicity associated with anemia.
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- 2019
4. Vaccines inducing immunity to Lassa virus glycoprotein and nucleoprotein protect macaques after a single shot
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Audrey Vallve, Laura Barrot, Caroline Picard, Nicolas Baillet, Sylvain Baize, Hervé Raoul, Mathieu Mateo, Frédéric Tangy, Emeline Perthame, Alexandra Journeaux, Stéphanie Reynard, Natalia Pietrosemoli, Jean Armengaud, Lyne Fellmann, Xavier Carnec, Richard Allan, Caroline Carbonnelle, Stéphane Barron, Catherine Legras-Lachuer, Kenzo-Hugo Hillion, Jean-Charles Gaillard, Marie-Agnès Dillies, Justine Schaeffer, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Viroscan3D SAS [Lyon, France], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire P4 Jean Mérieux-Inserm [Lyon] (Unité de service 3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Européen de Recherche en Virologie et Immunologie [Lyon] (Tour Inserm CERVI), Université de Strasbourg (UNISTRA), Laboratoire Innovations technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génomique virale et vaccination, This study was supported by the Grand Programme Fédérateur–Vaccinologie of the Institut Pasteur and the Fondation pour la Recherche Médicale (FRM team grant 2013). The MOPEVAC vaccine was supported by the LABEX ECOFECT (ANR-11-LABX-0048, Lyon University), within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007, French National Research Agency). The MeV-based LASV vaccines received funds from the Fondation pour l’Innovation en Infectiologie (FINOVI). M.M. was supported by a Pasteur Roux fellowship., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Male ,Proteomics ,030106 microbiology ,Biology ,medicine.disease_cause ,Measles ,Cell Line ,Measles virus ,03 medical and health sciences ,Viral Proteins ,Immune system ,Lassa Fever ,Immunity ,medicine ,Animals ,Humans ,Lassa fever ,Lassa virus ,Glycoproteins ,Vaccination ,General Medicine ,medicine.disease ,biology.organism_classification ,Flow Cytometry ,Virology ,3. Good health ,Nucleoprotein ,Macaca fascicularis ,030104 developmental biology ,Nucleoproteins ,Immunization ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology ,Transcriptome - Abstract
International audience; Lassa fever is a major threat in Western Africa. The large number of people living at risk for this disease calls for the development of a vaccine against Lassa virus (LASV). We generated live-attenuated LASV vaccines based on measles virus and Mopeia virus platforms and expressing different LASV antigens, with the aim to develop a vaccine able to protect after a single shot. We compared the efficacy of these vaccines against LASV in cynomolgus monkeys. The vaccines were well tolerated and protected the animals from LASV infection and disease after a single immunization but with varying efficacy. Analysis of the immune responses showed that complete protection was associated with robust secondary T cell and antibody responses against LASV. Transcriptomic and proteomic analyses showed an early activation of innate immunity and T cell priming after immunization with the most effective vaccines, with changes detectable as early as 2 days after immunization. The most efficacious vaccine candidate, a measles vector simultaneously expressing LASV glycoprotein and nucleoprotein, has been selected for further clinical evaluation.
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- 2019
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5. A Vaccine Platform against Arenaviruses Based on a Recombinant Hyperattenuated Mopeia Virus Expressing Heterologous Glycoproteins
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Stéphane Barron, Sylvain Baize, Elsie Laban Yekwa, Hervé Raoul, Audrey Page, Stéphanie Reynard, Mathieu Mateo, Xavier Carnec, Audrey Vallve, Laura Barrot, Jimmy Hortion, Caroline Picard, François Ferron, Caroline Carbonnelle, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Architecture et fonction des macromolécules biologiques (AFMB), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Laboratoire P4 Jean Mérieux-Inserm [Lyon] (Unité de service 3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Européen de Recherche en Virologie et Immunologie [Lyon] (Tour Inserm CERVI), This work was supported by the Fondation pour l'Innovation en Infectiologie (FINOVI) (Lyon, France), the Fondation pour la Recherche Médicale (FRM) (France), French National Research Agency grant ANR-11-BSV_019-02, and the Fondation Méditerranée Infection. This work was also supported by Labex Ecofect (grant ANR-11-LABX-0048, Lyon University) within the program Investissements d'Avenir (grant ANR-11-IDEX-0007, French National Research Agency)., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], ANR-11-IDEX-0007-02/11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), and ANR-11-IDEX-0007-02/11-IDEX-0007,Avenir L.S.E.,Avenir L.S.E.(2011)
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0301 basic medicine ,viruses ,MESH: Monkey Diseases/prevention & control ,viral hemorrhagic fevers ,MESH: Cricetinae ,medicine.disease_cause ,MESH: Lassa Fever/prevention & control ,MESH: Lassa Fever/virology ,Cricetinae ,Chlorocebus aethiops ,MESH: Animals ,Arenaviridae ,Lassa fever ,arenavirus ,innate immunity ,MESH: Arenaviridae/genetics ,biology ,MESH: Arenaviridae/immunology ,Viral Vaccine ,Monkey Diseases ,Vaccination ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] ,3. Good health ,Hemorrhagic Fevers ,MESH: Monkey Diseases/virology ,MESH: HEK293 Cells ,Interferon Type I ,MESH: Lassa virus/immunology ,MESH: Hemorrhagic Fevers, Viral/transmission ,MESH: Lassa Fever/immunology ,MESH: Interferon Type I/immunology ,MESH: Viral Vaccines/immunology ,Hemorrhagic Fevers, Viral ,live-vector vaccines ,Immunology ,MESH: Vero Cells ,MESH: Hemorrhagic Fevers, Viral/pathology ,Vaccines, Attenuated ,Microbiology ,Virus ,Cell Line ,03 medical and health sciences ,Virology ,Vaccines and Antiviral Agents ,medicine ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Lassa virus ,Vero Cells ,Arenavirus ,MESH: Humans ,MESH: Vaccines, Attenuated/immunology ,Viral Vaccines ,MESH: Monkey Diseases/immunology ,MESH: Vaccination ,biology.organism_classification ,medicine.disease ,MESH: Cercopithecus aethiops ,MESH: Hemorrhagic Fevers, Viral/immunology ,MESH: Exoribonucleases/metabolism ,MESH: Cell Line ,Macaca fascicularis ,HEK293 Cells ,030104 developmental biology ,MESH: Macaca fascicularis ,MESH: Hemorrhagic Fevers, Viral/virology ,Insect Science ,Junin virus ,Exoribonucleases - Abstract
Several Old World and New World arenaviruses are responsible for severe endemic and epidemic hemorrhagic fevers, whereas other members of the Arenaviridae family are nonpathogenic. To date, no approved vaccines, antivirals, or specific treatments are available, except for Junín virus. However, protection of nonhuman primates against Lassa fever virus (LASV) is possible through the inoculation of the closely related but nonpathogenic Mopeia virus (MOPV) before challenge with LASV. We reasoned that this virus, modified by using reverse genetics, would represent the basis for the generation of a vaccine platform against LASV and other pathogenic arenaviruses. After showing evidence of exoribonuclease (ExoN) activity in NP of MOPV, we found that this activity was essential for multiplication in antigen-presenting cells. The introduction of multiple mutations in the ExoN site of MOPV NP generated a hyperattenuated strain (MOPV ExoN6b ) that is (i) genetically stable over passages, (ii) has increased immunogenic properties compared to those of MOPV, and (iii) still promotes a strong type I interferon (IFN) response. MOPV ExoN6b was further modified to harbor the envelope glycoproteins of heterologous pathogenic arenaviruses, such as LASV or Lujo, Machupo, Guanarito, Chapare, or Sabia virus in order to broaden specific antigenicity while preserving the hyperattenuated characteristics of the parental strain. Our MOPV-based vaccine candidate for LASV, MOPEVAC LASV , was used in a one-shot immunization assay in nonhuman primates and fully protected them from a lethal challenge with LASV. Thus, our hyperattenuated strain of MOPV constitutes a promising new live-attenuated vaccine platform to immunize against several, if not all, pathogenic arenaviruses. IMPORTANCE Arenaviruses are emerging pathogens transmitted to humans by rodents and responsible for endemic and epidemic hemorrhagic fevers of global concern. Nonspecific symptoms associated with the onset of infection make these viruses difficult to distinguish from other endemic pathogens. Moreover, the unavailability of rapid diagnosis in the field delays the identification of the virus and early care for treatment and favors spreading. The vaccination of exposed populations would be of great help to decrease morbidity and human-to-human transmission. Using reverse genetics, we generated a vaccine platform for pathogenic arenaviruses based on a modified and hyperattenuated strain of the nonpathogenic Mopeia virus and showed that the Lassa virus candidate fully protected nonhuman primates from a lethal challenge. These results showed that a rationally designed recombinant MOPV-based vaccine is safe, immunogenic, and efficacious in nonhuman primates.
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- 2018
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6. One-shot immunization using a Measles/Lassa vaccine fully protects cynomolgus monkeys against Lassa fever
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M. Jourdain, Alexandra Fizet, Stéphanie Reynard, Audrey Vallve, Laura Barrot, Hervé Raoul, Nicolas Baillet, Caroline Carbonnelle, Stéphane Barron, Caroline Picard, Mathieu Mateo, Xavier Carnec, F. Tangy, Justine Schaeffer, and Sylvain Baize
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Microbiology (medical) ,One shot ,Infectious Diseases ,Immunization ,business.industry ,Medicine ,General Medicine ,business ,Lassa fever ,medicine.disease ,Measles ,Virology - Published
- 2019
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