9 results on '"Audrey Vallve"'
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2. Pathogenesis of recent Lassa virus isolates from lineages II and VII in cynomolgus monkeys
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Mathieu Mateo, Jimmy Hortion, Emeline Perthame, Caroline Picard, Stéphanie Reynard, Alexandra Journeaux, Clara Germain, Xavier Carnec, Nicolas Baillet, Virginie Borges-Cardoso, Natalia Pietrosemoli, Audrey Vallve, Stéphane Barron, Ophélie Jourjon, Orianne Lacroix, Aurélie Duthey, Manon Dirheimer, Maïlys Daniau, Catherine Legras-Lachuer, Gregory Jouvion, Caroline Carbonnelle, Hervé Raoul, and Sylvain Baize
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Lassa virus ,cynomolgus monkeys ,pathogenesis ,immune responses ,viral hemorrhagic fevers ,Infectious and parasitic diseases ,RC109-216 - Abstract
The area of Lassa virus (LASV) circulation is expanding, with the emergence of highly pathogenic new LASV lineages. Benin recently became an endemic country for LASV and has seen the emergence of a new LASV lineage (VII). The first two outbreaks in 2014 and 2016 showed a relatively high mortality rate compared to other outbreaks. We infected cynomolgus monkeys with two strains belonging to lineage II and lineage VII that were isolated from deceased patients during the 2016 outbreak in Benin. The lineage VII strain (L7) caused uniform mortality. Death was associated with uncontrolled viral replication, unbalanced inflammatory responses characterized by increased concentrations of pro- and anti-inflammatory mediators, and the absence of efficient immune responses, resembling the pathogenesis associated with the prototypic Josiah strain in monkeys. The lineage II strain (L2) showed apparently lower virulence than its counterpart, with a prolonged time to death and a lower mortality rate. Prolonged survival was associated with better control of viral replication, a moderate inflammatory response, and efficient T-cell responses. Transcriptomic analyses also highlighted important differences in the immune responses associated with the outcome. Both strains caused strong inflammation in several organs. Notably, meningitis and encephalitis were observed in the cerebral cortex and cerebellum in all monkeys, independently of the outcome. Due to their apparently high pathogenicity, emerging strains from lineage VII should be considered in preclinical vaccine testing. Lineage II would also be beneficial in pathogenesis studies to study the entire spectrum of Lassa fever severity.
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- 2022
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3. Systemic viral spreading and defective host responses are associated with fatal Lassa fever in macaques
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Nicolas Baillet, Stéphanie Reynard, Emeline Perthame, Jimmy Hortion, Alexandra Journeaux, Mathieu Mateo, Xavier Carnec, Justine Schaeffer, Caroline Picard, Laura Barrot, Stéphane Barron, Audrey Vallve, Aurélie Duthey, Frédéric Jacquot, Cathy Boehringer, Grégory Jouvion, Natalia Pietrosemoli, Rachel Legendre, Marie-Agnès Dillies, Richard Allan, Catherine Legras-Lachuer, Caroline Carbonnelle, Hervé Raoul, and Sylvain Baize
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Biology (General) ,QH301-705.5 - Abstract
Baillet et al. use the cynomolgus monkey model to model Lassa virus and associated Lassa fever (LF). They provide a full characterisation of LF pathogenesis with the aim of assisting the development of early diagnostic tools.
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- 2021
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4. Control of Nipah Virus Infection in Mice by the Host Adaptors Mitochondrial Antiviral Signaling Protein (MAVS) and Myeloid Differentiation Primary Response 88 (MyD88)
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Hervé Raoul, Audrey Vallve, Claire Dumont, Rodolphe Pelissier, Kévin P. Dhondt, Mathieu Iampietro, Julia Spanier, Branka Horvat, Noémie Aurine, Ulrich Kalinke, and TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
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0301 basic medicine ,mice ,Mice, Transgenic ,Nipah virus ,Biology ,Mitochondrion ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Interferon ,TLR ,medicine ,Animals ,Immunology and Allergy ,Receptor ,TRIF ,innate immunity ,Adaptor Proteins, Signal Transducing ,Mitochondrial antiviral-signaling protein ,Henipavirus Infections ,Mice, Knockout ,Innate immune system ,Toll-Like Receptors ,Nipah Virus ,interferon ,Interferon-beta ,MAVS ,MyD88 ,Virology ,In vitro ,030104 developmental biology ,Infectious Diseases ,Gene Expression Regulation ,Interferon Type I ,Myeloid Differentiation Factor 88 ,DEAD Box Protein 58 ,Signal transduction ,030215 immunology ,medicine.drug - Abstract
Interferon (IFN) type I plays a critical role in the protection of mice from lethal Nipah virus (NiV) infection, but mechanisms responsible for IFN-I induction remain unknown. In the current study, we demonstrated the critical role of the mitochondrial antiviral signaling protein signaling pathway in IFN-I production and NiV replication in murine embryonic fibroblasts in vitro, and the redundant but essential roles of both mitochondrial antiviral signaling protein and myeloid differentiation primary response 88 adaptors, but not toll/interleukin-1 receptor/resistance [TIR] domain–containing adaptor–inducing IFN-β (TRIF), in the control of NiV infection in mice. These results reveal potential novel targets for antiviral intervention and help in understanding NiV immunopathogenesis.
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- 2019
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5. A single-shot Lassa vaccine induces long-term immunity and protects cynomolgus monkeys against heterologous strains
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P. Moreau, Ophélie Jourjon, Virginie Borges-Cardoso, Caroline Picard, Manon Dirheimer, Xavier Carnec, Lyne Fellmann, Othmann Merabet, Clara Germain, Mathieu Mateo, Aurélie Duthey, Stéphanie Reynard, Alexandra Journeaux, Hervé Raoul, Jimmy Hortion, Frédéric Tangy, Gregory Jouvion, Audrey Vallve, Stéphane Barron, Caroline Carbonnelle, Nicolas Baillet, Orianne Lacroix, Sylvain Baize, 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), Laboratoire P4 - Jean Mérieux, Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), École nationale vétérinaire - Alfort (ENVA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Université de Strasbourg (UNISTRA), Génomique Virale et Vaccination, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This study was entirely funded by a grant from the Coalition for Epidemic Preparedness and Innovations (CEPI-CfP-001) to S. Baize, 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], Institut Pasteur [Paris]-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], École nationale vétérinaire d'Alfort (ENVA), Baize, Sylvain, and 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] (IP)
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0301 basic medicine ,viruses ,Heterologous ,medicine.disease_cause ,Measles virus ,03 medical and health sciences ,[SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology ,Lassa Fever ,0302 clinical medicine ,Immune system ,medicine ,Animals ,030212 general & internal medicine ,Vector (molecular biology) ,Lassa virus ,biology ,virus diseases ,Outbreak ,Viral Vaccines ,General Medicine ,Vaccine efficacy ,biology.organism_classification ,Virology ,3. Good health ,Nucleoprotein ,Africa, Western ,Macaca fascicularis ,Nucleoproteins ,030104 developmental biology ,[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology - Abstract
Acknowledgments: We thank P. Regnard (Silabe, Strasbourg) for medical care given to the monkeys. We thank S. Mundweiller, S. Godard, E. Moissonnier, D. Thomas, S. Mély, B. Labrosse, D. Pannetier, and C. Léculier (P4 INSERM–Jean Mérieux, US003, INSERM) for assistance in conducting the BSL-4 experiments. We are grateful to G. Fourcaud and B. Lafoux (Institut Pasteur, CIRI, Lyon) for technical help with histological studies. We thank S. Becker for providing us with the Josiah strain and T. G. Ksiasek, P. E. Rollin, and P. Jahrling for the LASV monoclonal antibodies. We also thank L. Branco (Zalgen Labs) for providing recombinant proteins. We are grateful to THEMIS Bioscience GmbH, a wholly owned subsidiary of Merck & Co. Inc. (E. Tauber, A. Kort, K. Ramsauer, S. Schrauf, Y. Tomberger, and R. Tschismarov), to the Coalition for Epidemic Preparedness and Innovations (R. Hatchett, G. Thiry, and M. Saville), and to C. Gerke (Department of Innovation Development, Institut Pasteur) for invaluable support; International audience; A safe and protective Lassa virus vaccine is crucially needed in Western Africa to stem the recurrent outbreaks of Lassa virus infections in Nigeria and the emergence of Lassa virus in previously unaffected countries, such as Benin and Togo. Major challenges in developing a Lassa virus vaccine include the high diversity of circulating strains and their reemergence from 1 year to another. To address each of these challenges, we immunized cynomolgus monkeys with a measles virus vector expressing the Lassa virus glycoprotein and nucleoprotein of the prototypic Lassa virus strain Josiah (MeV-NP). To evaluate vaccine efficacy against heterologous strains of Lassa virus, we challenged the monkeys a month later with heterologous strains from lineage II or lineage VII, finding that the vaccine was protective against these strains. A second cohort of monkeys was challenged 1 year later with the homologous Josiah strain, finding that a single dose of MeV-NP was sufficient to protect all vaccinated monkeys. These studies demonstrate that MeV-NP can generate both long-lasting immune responses and responses that are able to protect against diverse strains of Lassa virus.
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- 2021
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6. 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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7. 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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8. 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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9. Type I interferon signaling protects mice from lethal henipavirus infection
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Hervé Raoul, Marie Chalons, Cyrille Mathieu, Kévin P. Dhondt, Audrey Vallve, Joséphine M. Reynaud, Branka Horvat, 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), Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
MESH: Signal Transduction ,MESH: Interferon Type I ,encephalitis ,viruses ,MESH: Virus Internalization ,[SDV]Life Sciences [q-bio] ,MESH: Henipavirus Infections ,Nipah virus ,MESH: Virulence ,Antibodies, Viral ,Virus Replication ,medicine.disease_cause ,MESH: Mice, Knockout ,MESH: Antibodies, Neutralizing ,MESH: Hendra Virus ,Mice ,Hepatitis E virus ,Antibody Specificity ,Interferon ,Immunology and Allergy ,MESH: Animals ,Encephalitis, Viral ,MESH: Nipah Virus ,Cells, Cultured ,Henipavirus Infections ,Mice, Knockout ,0303 health sciences ,Virulence ,Brain ,virus diseases ,3. Good health ,MESH: Encephalitis, Viral ,Infectious Diseases ,MESH: Survival Analysis ,MESH: RNA, Viral ,Viruses ,Interferon Type I ,type I interferon ,RNA, Viral ,MESH: Neuroglia ,Neuroglia ,Encephalitis ,Signal Transduction ,medicine.drug ,Henipavirus ,MESH: Cells, Cultured ,MESH: Henipavirus ,Biology ,Hendra Virus ,Major Articles and Brief Reports ,03 medical and health sciences ,MESH: Brain ,Viral entry ,medicine ,Animals ,Humans ,MESH: Antibody Specificity ,MESH: Mice ,030304 developmental biology ,MESH: Humans ,030306 microbiology ,animal model ,MESH: Virus Replication ,Virus Internalization ,medicine.disease ,biology.organism_classification ,Antibodies, Neutralizing ,Survival Analysis ,Virology ,Disease Models, Animal ,Viral replication ,MESH: Disease Models, Animal ,Interferon type I ,MESH: Antibodies, Viral - Abstract
International audience; Hendra virus (HeV) and Nipah virus (NiV) are closely related, recently emerged paramyxoviruses that form Henipavirus genus and are capable of causing considerable morbidity and mortality in a number of mammalian species, including humans. However, in contrast to many other species and despite expression of functional virus entry receptors, mice are resistant to henipavirus infection. We report here the susceptibility of mice deleted for the type I interferon receptor (IFNAR-KO) to both HeV and NiV. Intraperitoneally infected mice developed fatal encephalitis, with pathology and immunohistochemical features similar to what was found in humans. Viral RNA was found in the majority of analyzed organs, and sublethally infected animals developed virus-specific neutralizing antibodies. Altogether, these results reveal IFNAR-KO mice as a new small animal model to study HeV and NiV pathogenesis, prophylaxis, and treatment and suggest the critical role of type I interferon signaling in the control of henipavirus infection.
- Published
- 2013
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