20 results on '"Sergio Gómez-Medina"'
Search Results
2. Sustained Elevated Cytokine Levels during Recovery Phase of Mayaro Virus Infection
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Dennis Tappe, José Vicente Pérez-Girón, Gudrun Just-Nübling, Gernot Schuster, Sergio Gómez-Medina, Stephan Günther, César Muñoz-Fontela, and Jonas Schmidt-Chanasit
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Mayaro virus ,arthralgia ,cytokine ,inflammation ,alphavirus ,travel ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Published
- 2016
- Full Text
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3. Chikungunya Outbreak in the Republic of the Congo, 2019-Epidemiological, Virological and Entomological Findings of a South-North Multidisciplinary Taskforce Investigation
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Fabrizio Carletti, Martina Rueca, Martin Parfait Aimè Coussoud-Mavoungou, Francesca Colavita, Maria Rosaria Capobianchi, Chiara Montaldo, Emanuela Giombini, Richard Kock, Najmul Haider, Cesare Ernesto Maria Gruber, Antonino Di Caro, Jacqueline Lydia Mikolo, Beatriz Escudero-Pérez, Concetta Castilletti, Vincent J. Munster, Stephanie N. Seifert, Biez Ulrich Judicaël, Emily V Nelson, Leonard E. G. Mboera, César Muñoz-Fontela, Vincenzo Puro, Robert J. Fischer, Francesco Vairo, Patrick K. Tungu, Francesco Messina, Francine Ntoumi, Emanuele Nicastri, Lambert Kitembo, Steve Diafouka-Diatela, Marco Iannetta, Barbara Bartolini, Giuseppe Ippolito, Alimuddin Zumla, Chantal Portella, Sergio Gómez-Medina, and Simone Lanini
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0301 basic medicine ,Male ,chikungunya ,Republic of Congo ,lcsh:QR1-502 ,medicine.disease_cause ,lcsh:Microbiology ,Disease Outbreaks ,0302 clinical medicine ,Aedes ,Chikungunya ,Aedes spp ,Child ,Phylogeny ,Phylogenetic tree ,virus diseases ,Middle Aged ,Infectious Diseases ,Congo ,Child, Preschool ,Larva ,Enzootic ,Sylvatic cycle ,Female ,Chikungunya virus ,Adult ,Adolescent ,030231 tropical medicine ,mosquito ,Mosquito Vectors ,Biology ,Arbovirus ,Article ,03 medical and health sciences ,Young Adult ,Virology ,medicine ,Animals ,Humans ,outbreak ,Outbreak ,Bayes Theorem ,medicine.disease ,biology.organism_classification ,Settore MED/17 ,030104 developmental biology ,arbovirus ,Vector (epidemiology) ,Mutation ,Chikungunya Fever ,ONE-HEALTH - Abstract
The Republic of Congo (RoC) declared a chikungunya (CHIK) outbreak on 9 February 2019. We conducted a ONE-Human-Animal HEALTH epidemiological, virological and entomological investigation. Methods: We collected national surveillance and epidemiological data. CHIK diagnosis was based on RT-PCR and CHIKV-specific antibodies. Full CHIKV genome sequences were obtained by Sanger and MinION approaches and Bayesian tree phylogenetic analysis was performed. Mosquito larvae and 215 adult mosquitoes were collected in different villages of Kouilou and Pointe-Noire districts and estimates of Aedes (Ae.) mosquitos’ CHIKV-infectious bites obtained. We found two new CHIKV sequences of the East/Central/South African (ECSA) lineage, clustering with the recent enzootic sub-clade 2, showing the A226V mutation. The RoC 2019 CHIKV strain has two novel mutations, E2-T126M and E2-H351N. Phylogenetic suggests a common origin from 2016 Angola strain, from which it diverged around 1989 (95% HPD 1985–1994). The infectious bite pattern was similar for 2017, 2018 and early 2019. One Ae. albopictus pool was RT-PCR positive. The 2019 RoC CHIKV strain seems to be recently introduced or be endemic in sylvatic cycle. Distinct from the contemporary Indian CHIKV isolates and in contrast to the original Central-African strains (transmitted by Ae. aegypti), it carries the A226V mutation, indicating an independent adaptive mutation in response to vector replacement (Ae. albopictus vs Ae. aegypti).
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- 2020
4. Severe Human Lassa Fever Is Characterized by Nonspecific T-Cell Activation and Lymphocyte Homing to Inflamed Tissues
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Stephan Günther, Donatus I Adomeh, Susanne Krasemann, Catherine Olal, Emily V Nelson, Jennifer Oyakhliome, Beatriz Escudero-Pérez, Ephraim Ogbani-Emovon, César Muñoz-Fontela, Lisa Oestereich, Danny Asogun, Monika Rottstegge, Thomas Olokor, Anita K. McElroy, Emmanuel Omomoh, Elisa Pallasch, Jonas Müller, Sergio Gómez-Medina, David M. Wozniak, Beate Becker-Ziaja, Yemisi Ighodalo, Julia R Port, and Kristin Hartmann
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CD4-Positive T-Lymphocytes ,Male ,viruses ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,Lymphocyte Activation ,Severity of Illness Index ,Disease Outbreaks ,Mice ,0302 clinical medicine ,Immunopathology ,host response ,Intestinal Mucosa ,Lassa fever ,Child ,Skin ,0303 health sciences ,Integrin beta1 ,pathogenesis ,virus diseases ,Middle Aged ,medicine.anatomical_structure ,Child, Preschool ,Female ,Adult ,Adolescent ,T cell ,Immunology ,T cells ,Nigeria ,Biology ,Microbiology ,Sierra leone ,Viral hemorrhagic fever ,03 medical and health sciences ,Interferon-gamma ,Lassa Fever ,Lysosomal-Associated Membrane Protein 1 ,Virology ,medicine ,Animals ,Humans ,viral hemorrhagic fever ,Lymphocyte homing receptor ,Lassa virus ,030304 developmental biology ,Aged ,Retrospective Studies ,Tumor Necrosis Factor-alpha ,Infant, Newborn ,Infant ,HLA-DR Antigens ,medicine.disease ,Survival Analysis ,Gene Expression Regulation ,Insect Science ,T-cell homing ,Pathogenesis and Immunity ,030215 immunology ,Homing (hematopoietic) - Abstract
Lassa fever may cause severe disease in humans, in particular in areas of endemicity like Sierra Leone and Nigeria. Despite its public health importance, the pathophysiology of Lassa fever in humans is poorly understood. Here, we present clinical immunology data obtained in the field during the 2018 Lassa fever outbreak in Nigeria indicating that severe Lassa fever is associated with activation of T cells antigenically unrelated to Lassa virus and poor Lassa virus-specific effector T-cell responses. Mechanistically, we show that these bystander T cells express defined tissue homing signatures that suggest their recruitment to inflamed tissues and a putative role of these T cells in immunopathology. These findings open a window of opportunity to consider T-cell targeting as a potential postexposure therapeutic strategy against severe Lassa fever, a hypothesis that could be tested in relevant animal models, such as nonhuman primates., Lassa fever (LF) is a zoonotic viral hemorrhagic fever caused by Lassa virus (LASV), which is endemic to West African countries. Previous studies have suggested an important role for T-cell-mediated immunopathology in LF pathogenesis, but the mechanisms by which T cells influence disease severity and outcome are not well understood. Here, we present a multiparametric analysis of clinical immunology data collected during the 2017–2018 Lassa fever outbreak in Nigeria. During the acute phase of LF, we observed robust activation of the polyclonal T-cell repertoire, which included LASV-specific and antigenically unrelated T cells. However, severe and fatal LF cases were characterized by poor LASV-specific effector T-cell responses. Severe LF was also characterized by the presence of circulating T cells with homing capacity to inflamed tissues, including the gut mucosa. These findings in LF patients were recapitulated in a mouse model of LASV infection, in which mucosal exposure resulted in remarkably high lethality compared to skin exposure. Taken together, our findings indicate that poor LASV-specific T-cell responses and activation of nonspecific T cells with homing capacity to inflamed tissues are associated with severe LF. IMPORTANCE Lassa fever may cause severe disease in humans, in particular in areas of endemicity like Sierra Leone and Nigeria. Despite its public health importance, the pathophysiology of Lassa fever in humans is poorly understood. Here, we present clinical immunology data obtained in the field during the 2018 Lassa fever outbreak in Nigeria indicating that severe Lassa fever is associated with activation of T cells antigenically unrelated to Lassa virus and poor Lassa virus-specific effector T-cell responses. Mechanistically, we show that these bystander T cells express defined tissue homing signatures that suggest their recruitment to inflamed tissues and a putative role of these T cells in immunopathology. These findings open a window of opportunity to consider T-cell targeting as a potential postexposure therapeutic strategy against severe Lassa fever, a hypothesis that could be tested in relevant animal models, such as nonhuman primates.
- Published
- 2020
5. Ebola Virus Disease Survivors Show More Efficient Antibody Immunity than Vaccinees Despite Similar Levels of Circulating Immunoglobulins
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Matthias Pillny, Marylyn M. Addo, Till Koch, N’Faly Magassouba, Fara Raymond Koundouno, Emily V Nelson, Paula Ruibal, César Muñoz-Fontela, Sergio Gómez-Medina, Stephan Günther, My L Ly, Beatriz Escudero-Pérez, Christine Dahlke, Miles W. Carroll, Joseph Akoi Bore, and Monika Rottstegge
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0301 basic medicine ,Adult ,Male ,viruses ,030106 microbiology ,lcsh:QR1-502 ,Immunoglobulins ,Disease ,Immunological memory ,medicine.disease_cause ,Antibodies, Viral ,immune memory ,lcsh:Microbiology ,Article ,03 medical and health sciences ,Ebola virus ,Viral Envelope Proteins ,Immunity ,Virology ,vaccine ,medicine ,Humans ,antibodies ,Survivors ,Ebola Vaccines ,biology ,business.industry ,Vaccination ,virus diseases ,Vesiculovirus ,Hemorrhagic Fever, Ebola ,Viral Load ,biology.organism_classification ,Ebolavirus ,Antibodies, Neutralizing ,Clinical trial ,030104 developmental biology ,Infectious Diseases ,Vesicular stomatitis virus ,VSV ,biology.protein ,Female ,Antibody ,business ,Immunologic Memory - Abstract
The last seven years have seen the greatest surge of Ebola virus disease (EVD) cases in equatorial Africa, including the 2013&ndash, 2016 epidemic in West Africa and the recent epidemics in the Democratic Republic of Congo (DRC). The vaccine clinical trials that took place in West Africa and the DRC, as well as follow-up studies in collaboration with EVD survivor communities, have for the first time allowed researchers to compare immune memory induced by natural infection and vaccination. These comparisons may be relevant to evaluate the putative effectiveness of vaccines and candidate medical countermeasures such as convalescent plasma transfer. In this study, we compared the long-term functionality of anti-EBOV glycoprotein (GP) antibodies from EVD survivors with that from volunteers who received the recombinant vesicular stomatitis virus vectored vaccine (rVSV-ZEBOV) during the Phase I clinical trial in Hamburg. Our study highlights important differences between EBOV vaccination and natural infection and provides a framework for comparison with other vaccine candidates.
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- 2020
6. Regulation of the Ebola Virus VP24 Protein by SUMO
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Santiago Vidal, Dolores Rodríguez, César Muñoz-Fontela, María Teresa Rejas, Carmen San Martín, Rosa Barrio, Viktorija Preitakaite, Maite Baz-Martínez, James D. Sutherland, Sergio Gómez-Medina, Rocío Seoane, Yanis Hichem Bouzaher, Ahmed El Motiam, Carmen Rivas, Manuel S. Rodriguez, Ministerio de Economía y Competitividad (España), Xunta de Galicia, German Center for Infection Research, European Commission, CIMUS Biomedical Research Institute [Santiago de Compostela], Functional Genomics, CIC Biogune, Environmental Engineering Research Centre, Universidad de los Andes [Bogota] (UNIANDES), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Molecular and Cellular Biology
- Subjects
Models, Molecular ,Protein Conformation ,[SDV]Life Sciences [q-bio] ,viruses ,medicine.disease_cause ,Deubiquitinating enzyme ,Ubiquitin-Specific Peptidase 7 ,Ebola virus ,Ubiquitin ,Interferon ,Chlorocebus aethiops ,Monoubiquitination ,0303 health sciences ,biology ,SUMO ,USP7 ,VP24 ,ubiquitin ,030302 biochemistry & molecular biology ,Ebolavirus ,Virus-Cell Interactions ,3. Good health ,Cell biology ,Protein Transport ,STAT1 Transcription Factor ,Host-Pathogen Interactions ,Interferon Type I ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Protein Binding ,Signal Transduction ,medicine.drug ,alpha Karyopherins ,Viral protein ,SUMO-1 Protein ,Immunology ,Microbiology ,Virus ,Viral Proteins ,03 medical and health sciences ,VP40 ,Protein Domains ,Virology ,medicine ,Animals ,Humans ,Vero Cells ,030304 developmental biology ,Binding Sites ,Sumoylation ,Immunity, Innate ,HEK293 Cells ,Gene Expression Regulation ,Insect Science ,Mutation ,biology.protein ,HeLa Cells - Abstract
Some viruses take advantage of conjugation of ubiquitin or ubiquitin-like proteins to enhance their own replication. One example is Ebola virus, which has evolved strategies to utilize these modification pathways to regulate the viral proteins VP40 and VP35 and to counteract the host defenses. Here, we show a novel mechanism by which Ebola virus exploits the ubiquitin and SUMO pathways. Our data reveal that minor matrix protein VP24 of Ebola virus is a bona fide SUMO target. Analysis of a SUMOylation-defective VP24 mutant revealed a reduced ability to block the type I interferon (IFN) pathway and to inhibit IFN-mediated STAT1 nuclear translocation, exhibiting a weaker interaction with karyopherin 5 and significantly diminished stability. Using glutathione S-transferase (GST) pulldown assay, we found that VP24 also interacts with SUMO in a noncovalent manner through a SIM domain. Mutation of the SIM domain in VP24 resulted in a complete inability of the protein to downmodulate the IFN pathway and in the monoubiquitination of the protein. We identified SUMO deubiquitinating enzyme ubiquitin-specific-processing protease 7 (USP7) as an interactor and a negative modulator of VP24 ubiquitination. Finally, we show that mutation of one ubiquitination site in VP24 potentiates the IFN modulatory activity of the viral protein and its ability to block IFN-mediated STAT1 nuclear translocation, pointing to the ubiquitination of VP24 as a negative modulator of the VP24 activity. Altogether, these results indicate that SUMO interacts with VP24 and promotes its USP7-mediated deubiquitination, playing a key role in the interference with the innate immune response mediated by the viral protein.IMPORTANCE The Ebola virus VP24 protein plays a critical role in escape of the virus from the host innate immune response. Therefore, deciphering the molecular mechanisms modulating VP24 activity may be useful to identify potential targets amenable to therapeutics. Here, we identify the cellular proteins USP7, SUMO, and ubiquitin as novel interactors and regulators of VP24. These interactions may represent novel potential targets to design new antivirals with the ability to modulate Ebola virus replication., Funding at the laboratory of C.R. is provided by Ministry of Science, Innovation and Universities and FEDER (BFU-2017-88880-P). C.R. also acknowledges grants GRC GI-2119 (Xunta de Galicia) and SAF2017-90900-REDT (UBIRed Program). S.V. is a predoctoral fellow funded by Xunta de Galicia. M.B.-M. is a postdoctoral fellow funded by Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria). A.E.M. is the recipient of a fellowship of the Spanish FPI program. This work was partially funded by the German Center for Infection Research (DZIF TTU 01.702_00 to C.M.-F.). R.B. and J.D.S. acknowledge grants BFU2017-84653-P (MINECO/FEDER, EU), SEV-2016-0644 (Severo Ochoa Excellence Program), 765445-EU (UbiCODE Program), and SAF2017- 90900-REDT (UBIRed Program). C.S.M. acknowledges grant BFU2016-74868-P.
- Published
- 2019
7. Monocyte-derived dendritic cells enhance protection against secondary influenza challenge by controlling the switch in CD8+ T-cell immunodominance
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Paula Ruibal, Juliana Idoyaga, César Muñoz-Fontela, Anja Lüdtke, Sergio Gómez-Medina, Jazmina L. G. Cruz, and José Vicente Pérez-Girón
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0301 basic medicine ,Monocyte ,Immunology ,Dendritic cell ,Immunodominance ,Biology ,Virology ,Virus ,Nucleoprotein ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,medicine ,biology.protein ,Immunology and Allergy ,Cytotoxic T cell ,CD8 ,Polymerase - Abstract
Influenza virus infection triggers an increase in the number of monocyte-derived dendritic cells (moDCs) in the respiratory tract, but the role of these cells during antiviral immunity is still unclear. Here we show that during influenza infection, moDCs dominate the late activation of CD8+ T cells and trigger the switch in immunodominance of the CD8+ T-cell response from acidic polymerase specificity to nucleoprotein specificity. Abrogation of monocyte recruitment or depletion of moDCs strongly compromised host resistance to secondary influenza challenge. These findings underscore a novel function of moDCs in the antiviral response to influenza virus, and have important implications for vaccine design.
- Published
- 2016
8. Comparative pathogenesis of Ebola virus and Reston virus infection in humanized mice
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Anja Lüdtke, Jürgen Müller-Guhl, Monika Rottstegge, Julia R Port, Susanne Krasemann, Estefanía Rodríguez, César Muñoz-Fontela, Paula Ruibal, Kristin Hartmann, Beatriz Escudero-Pérez, Emily V Nelson, and Sergio Gómez-Medina
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0301 basic medicine ,viruses ,Virulence ,Disease ,Mice, SCID ,Biology ,medicine.disease_cause ,Virus Replication ,Mouse models ,Virus ,Pathogenesis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Mice, Inbred NOD ,Virology ,medicine ,Animals ,Humans ,Ebolavirus ,Infectious disease ,Ebola virus ,Mucous Membrane ,General Medicine ,Hemorrhagic Fever, Ebola ,Viral Load ,3. Good health ,Disease Models, Animal ,030104 developmental biology ,Viral replication ,Infectious disease (medical specialty) ,030220 oncology & carcinogenesis ,Research Article - Abstract
Filoviruses of the genus Ebolavirus include 6 species with marked differences in their ability to cause disease in humans. From the highly virulent Ebola virus to the seemingly nonpathogenic Reston virus, case fatality rates can range between 0% and 90%. In order to understand the molecular basis of these differences, it is imperative to establish disease models that recapitulate human disease as faithfully as possible. Nonhuman primates (NHPs) are the gold-standard models for filovirus pathogenesis, but comparative studies are skewed by the fact that Reston virus infection can be lethal for NHPs. Here we used HLA-A2–transgenic, NOD–scid–IL-2γ receptor–knockout (NSG-A2) mice reconstituted with human hematopoiesis to compare Ebola virus and Reston virus pathogenesis in a human-like environment. While markedly less pathogenic than Ebola virus, Reston virus killed 20% of infected mice, a finding that was linked to exacerbated inflammation and viral replication in the liver. In addition, the case fatality ratios of different Ebolavirus species in humans were recapitulated in the humanized mice. Our findings point to humanized mice as a putative model to test the pathogenicity of newly discovered filoviruses, and suggest that further investigations on Reston virus pathogenesis in humans are warranted., Humanized mice reconstituted with human hematopoiesis recapitulate the pathogenicity of all ebolaviruses.
- Published
- 2018
9. Humanized Mice Reproduce Acute and Persistent Human Adenovirus Infection
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Gundula Pilnitz-Stolze, Wing Hang Ip, Estefanía Rodríguez, Thomas Dobner, Sergio Gómez-Medina, César Muñoz-Fontela, Nilgün Tekin, Viktoria Kolbe, Kristin Hartmann, and Susanne Krasemann
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0301 basic medicine ,030106 microbiology ,Mice, Transgenic ,Viremia ,Adaptive Immunity ,Biology ,Adenovirus Infections, Human ,Immunocompromised Host ,Mice ,03 medical and health sciences ,Immune system ,Bone Marrow ,medicine ,Animals ,Humans ,Immunology and Allergy ,Adenovirus infection ,Asymptomatic Infections ,Adenoviruses, Human ,virus diseases ,Viral Load ,medicine.disease ,Acquired immune system ,Virology ,eye diseases ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Liver ,Acute Disease ,DNA, Viral ,Immunology ,Humanized mouse ,Bone marrow ,Viral hepatitis ,Viral load - Abstract
Severe human adenovirus (HAdV) infections are an increasing threat for immunosuppressed individuals, particularly those who have received stem cell transplants. It has been previously hypothesized that severe infections might be due to reactivation of a persistent infection, but this hypothesis has been difficult to test owing to the lack of a permissive in vivo model of HAdV infection. Here we established a humanized mouse model that reproduces features of acute and persistent HAdV infection. In this model, acute infection correlated with high mortality, weight loss, liver pathology, and expression of viral proteins in several organs. In contrast, persistent infection was asymptomatic and led to establishment of HAdV-specific adaptive immunity and expression of early viral genes exclusively in the bone marrow. These findings validate the use of humanized mice to study acute and persistent HAdV infection and strongly suggest the presence of cellular reservoirs in the bone marrow.
- Published
- 2016
10. Distinct Immunogenicity and Efficacy of Poxvirus-Based Vaccine Candidates against Ebola Virus Expressing GP and VP40 Proteins
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Mariano Esteban, Karl Ljungberg, Mart Ustav, Peter Liljeström, Lucas Sánchez-Sampedro, César Muñoz-Fontela, Juan García-Arriaza, Adrián Lázaro-Frías, and Sergio Gómez-Medina
- Subjects
0301 basic medicine ,Zaire ebolavirus ,Neutrophils ,viruses ,Chick Embryo ,Antibodies, Viral ,medicine.disease_cause ,Sudan ,Mice ,chemistry.chemical_compound ,Vaccines, DNA ,Mice, Inbred BALB C ,biology ,Immunogenicity ,Vaccination ,Ebolavirus ,Killer Cells, Natural ,Democratic Republic of the Congo ,Chemokines ,Immunology ,Sudan ebolavirus ,complex mixtures ,Microbiology ,Virus ,Viral Matrix Proteins ,03 medical and health sciences ,Immune system ,VP40 ,Cell Line, Tumor ,Virology ,Vaccines and Antiviral Agents ,medicine ,Animals ,Humans ,Ebola Vaccines ,Glycoproteins ,Ebola virus ,Viral Vaccines ,Dendritic Cells ,Interferon-beta ,Hemorrhagic Fever, Ebola ,biology.organism_classification ,HEK293 Cells ,030104 developmental biology ,chemistry ,Immunoglobulin G ,Insect Science ,Vaccinia ,HeLa Cells - Abstract
Zaire and Sudan ebolavirus species cause a severe disease in humans and nonhuman primates (NHPs) characterized by a high mortality rate. There are no licensed therapies or vaccines against Ebola virus disease (EVD), and the recent 2013 to 2016 outbreak in West Africa highlighted the need for EVD-specific medical countermeasures. Here, we generated and characterized head-to-head the immunogenicity and efficacy of five vaccine candidates against Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV) based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA) expressing either the virus glycoprotein (GP) or GP together with the virus protein 40 (VP40) forming virus-like particles (VLPs). In a human monocytic cell line, the different MVA vectors (termed MVA-EBOVs and MVA-SUDVs) triggered robust innate immune responses, with production of beta interferon (IFN-β), proinflammatory cytokines, and chemokines. Additionally, several innate immune cells, such as dendritic cells, neutrophils, and natural killer cells, were differentially recruited in the peritoneal cavity of mice inoculated with MVA-EBOVs. After immunization of mice with a homologous prime/boost protocol (MVA/MVA), total IgG antibodies against GP or VP40 from Zaire and Sudan ebolavirus were differentially induced by these vectors, which were mainly of the IgG1 and IgG3 isotypes. Remarkably, an MVA-EBOV construct coexpressing GP and VP40 protected chimeric mice challenged with EBOV to a greater extent than a vector expressing GP alone. These results support the consideration of MVA-EBOVs and MVA-SUDVs expressing GP and VP40 and producing VLPs as best-in-class potential vaccine candidates against EBOV and SUDV. IMPORTANCE EBOV and SUDV cause a severe hemorrhagic fever affecting humans and NHPs. Since their discovery in 1976, they have caused several sporadic epidemics, with the recent outbreak in West Africa from 2013 to 2016 being the largest and most severe, with more than 11,000 deaths being reported. Although some vaccines are in advanced clinical phases, less expensive, safer, and more effective licensed vaccines are desirable. We generated and characterized head-to-head the immunogenicity and efficacy of five novel vaccines against EBOV and SUDV based on the poxvirus MVA expressing GP or GP and VP40. The expression of GP and VP40 leads to the formation of VLPs. These MVA-EBOV and MVA-SUDV recombinants triggered robust innate and humoral immune responses in mice. Furthermore, MVA-EBOV recombinants expressing GP and VP40 induced high protection against EBOV in a mouse challenge model. Thus, MVA expressing GP and VP40 and producing VLPs is a promising vaccine candidate against EBOV and SUDV.
- Published
- 2018
11. Ebola Virus Disease in Mice with Transplanted Human Hematopoietic Stem Cells
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Sabrina Bockholt, Stephanie Wurr, Anja Lüdtke, Wing Hang Ip, Carol Stocking, Toni Rieger, Paula Ruibal, César Muñoz-Fontela, Stephan Günther, Elisa Pallasch, Lisa Oestereich, Sergio Gómez-Medina, and Estefanía Rodríguez
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viruses ,medicine.medical_treatment ,Immunology ,Hemorrhage ,Viremia ,Kaplan-Meier Estimate ,Hematopoietic stem cell transplantation ,Disease ,Biology ,medicine.disease_cause ,Microbiology ,Mice ,Mice, Inbred NOD ,Virology ,medicine ,Animals ,Humans ,Ebolavirus ,Ebola virus ,Fatty liver ,Hematopoietic Stem Cell Transplantation ,virus diseases ,Hemorrhagic Fever, Ebola ,medicine.disease ,Fatty Liver ,Disease Models, Animal ,Haematopoiesis ,Microscopy, Fluorescence ,Insect Science ,Heterografts ,Pathogenesis and Immunity ,Stem cell - Abstract
The development of treatments for Ebola virus disease (EVD) has been hampered by the lack of small-animal models that mimick human disease. Here we show that mice with transplanted human hematopoetic stem cells reproduce features typical of EVD. Infection with Ebola virus was associated with viremia, cell damage, liver steatosis, signs of hemorrhage, and high lethality. Our study provides a small-animal model with human components for the development of EVD therapies.
- Published
- 2015
12. Sustained Elevated Cytokine Levels during Recovery Phase of Mayaro Virus Infection
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Gernot Schuster, José Vicente Pérez-Girón, Sergio Gómez-Medina, Jonas Schmidt-Chanasit, Stephan Günther, Dennis Tappe, César Muñoz-Fontela, and Gudrun Just-Nübling
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0301 basic medicine ,myalgia ,Male ,Letter ,Epidemiology ,Arthritis ,lcsh:Medicine ,medicine.disease_cause ,Antibodies, Viral ,Gastroenterology ,Serology ,Germany ,cytokine ,Chikungunya ,travel ,media_common ,biology ,Convalescence ,imported infection ,Infectious Diseases ,C-Reactive Protein ,Joint pain ,Host-Pathogen Interactions ,Cytokines ,Female ,medicine.symptom ,Microbiology (medical) ,Adult ,medicine.medical_specialty ,Fever ,media_common.quotation_subject ,030106 microbiology ,Alphavirus ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Internal medicine ,medicine ,Sustained Elevated Cytokine Levels during Recovery Phase of Mayaro Virus Infection ,Animals ,Humans ,lcsh:RC109-216 ,viruses ,Alphavirus infection ,arthralgia ,Letters to the Editor ,business.industry ,Alphavirus Infections ,C-reactive protein ,lcsh:R ,South America ,medicine.disease ,Mayaro virus ,Insect Vectors ,030104 developmental biology ,arbovirus ,Culicidae ,inflammation ,Immunology ,biology.protein ,business - Abstract
To the Editor: Mayaro virus (MAYV), a mosquitoborne alphavirus endemic to South America, causes a self-limiting febrile arthralgia syndrome closely resembling Chikungunya fever (1). MAYV has been detected increasingly as imported infections in international travelers returning to Europe and North America (2–9). Joint pain, the most prominent symptom, is often long-lasting (several months), sometimes incapacitating (4,6,7,9), and may recur (8). Arthralgia develops during the acute phase and symmetrically affects the wrists, ankles, and small joints of hands and feet. Joint swelling may occur initially, but permanent joint damage has not been described (5). The clinical disease and diagnostic procedures have been described (1–9), but immunologic parameters and their possible role in the clinical follow-up of patients (i.e., during the postacute long-lasting arthralgia period) remain to be investigated. To further our knowledge of MAYV infection, we analyzed cytokine levels in serum samples from 6 travelers to South America who returned to Europe with Mayaro fever (MF). Two of the cases occurred during 2014; 4 occurred during 2011–2013 (2–5). The 6 travelers comprised 2 men and 4 women who were 20–54 (median 36) years of age (Technical Appendix Table). The 2 most recent cases occurred in spring 2014 in a 28-year-old female student and a 54-year-old male physician. Serologic testing was performed for both patients at the Bernhard Nocht Institute and confirmed by virus neutralization testing (4). The student had traveled for 3 weeks in Ecuador, visiting rainforest villages and hiking in the jungle. During her stay, she had experienced myalgia of the forearms, arthralgia of fingers and toes, subfebrile but elevated body temperatures, and maculopapular exanthema. On examination in Germany, the student had no clinical signs of disease, but she reported arthralgia of the ankles and hands. Laboratory test results showed a slightly increased C-reactive protein level (6.2 mg/L, reference value 12 months. In the examined patients, the prolonged arthralgia recovery phase was paralleled by significantly increased proinflammatory cytokine levels, indicating ongoing inflammation, probably related to arthritis. Elevated levels of RANTES and IP-10 suggest T-cell recruitment, possibly reflecting virus persistence and replication, as described for the related Chikungunya virus (10). Thus, cytokine measurements may be helpful for monitoring patient symptoms, especially when signs of arthritis (swellings and redness) and elevated standard serum inflammatory parameters are no longer present. In our study, the picture of MF cytokine elevations paralleled those described for Chikungunya virus infection (10); these elevated levels may help to elucidate the pathogenesis of MAYV-induced arthralgia. More immunology data are required to complete this evolving picture of viral arthralgia syndromes. Technical Appendix: International travelers who were recently diagnosed with Mayaro fever and were included in this study. Click here to view.(151K, pdf)
- Published
- 2016
13. Novel Cross-Reactive Monoclonal Antibodies against Ebolavirus Glycoproteins Show Protection in a Murine Challenge Model
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Lisa Oestereich, Adolfo García-Sastre, Benjamin R. tenOever, Fatima Amanat, Florian Krammer, James Duehr, Sergio Gómez-Medina, Veronika Chromikova, Ignacio Mena, Teddy John Wohlbold, César Muñoz-Fontela, Christopher F. Basler, and Madhusudan Rajendran
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0301 basic medicine ,Zaire ebolavirus ,medicine.drug_class ,Cross Protection ,Immunology ,Biology ,Antibodies, Viral ,medicine.disease_cause ,Monoclonal antibody ,Microbiology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Viral Envelope Proteins ,Virology ,Vaccines and Antiviral Agents ,medicine ,Animals ,Immunologic Factors ,030212 general & internal medicine ,Ebolavirus ,chemistry.chemical_classification ,Ebola virus ,Antibody-Dependent Cell Cytotoxicity ,Antibodies, Monoclonal ,Hemorrhagic Fever, Ebola ,biology.organism_classification ,Disease Models, Animal ,Treatment Outcome ,030104 developmental biology ,chemistry ,Vesicular stomatitis virus ,Insect Science ,Humoral immunity ,biology.protein ,Antibody ,Glycoprotein - Abstract
Out of an estimated 31,100 cases since their discovery in 1976, ebolaviruses have caused approximately 13,000 deaths. The vast majority (∼11,000) of these occurred during the 2013-2016 West African epidemic. Three out of five species in the genus are known to cause Ebola Virus Disease in humans. Several monoclonal antibodies against the ebolavirus glycoprotein are currently in development as therapeutics. However, there is still a paucity of monoclonal antibodies that can cross-react between the glycoproteins of different ebolavirus species, and the mechanism of these monoclonal antibody therapeutics is still not understood in detail. Here, we generated a panel of eight murine monoclonal antibodies (MAbs) utilizing a prime-boost vaccination regimen with a Zaire ebolavirus glycoprotein expression plasmid followed by infection with a vesicular stomatitis virus expressing the Zaire ebolavirus glycoprotein. We tested the binding breadth of the resulting monoclonal antibodies using a set of recombinant surface glycoproteins from Reston, Taï Forest, Bundibugyo, Zaire, Sudan, and Marburg viruses and found two antibodies that showed pan-ebolavirus binding. An in vivo Stat2 −/− mouse model was utilized to test the ability of these MAbs to protect from infection with a vesicular stomatitis virus expressing the Zaire ebolavirus glycoprotein. Several of our antibodies, including the broadly binding ones, protected mice from mortality despite lacking neutralization capability in vitro , suggesting their protection may be mediated by Fc-FcR interactions. Indeed, three antibodies displayed cellular phagocytosis and/or antibody-dependent cell-mediated cytotoxicity in vitro . Our antibodies, specifically the two identified cross-reactive monoclonal antibodies (KL-2E5 and KL-2H7), might add to the understanding of anti-ebolavirus humoral immunity. IMPORTANCE This study describes the generation of a panel of novel anti-ebolavirus glycoprotein monoclonal antibodies, including two antibodies with broad cross-reactivity to all known ebolavirus species. The antibodies were raised using a heterologous DNA-viral vector prime-boost regimen, resulting in a high proportion of cross-reactive antibodies (25%). Similar vaccination regimens have been used successfully to induce broad protection against influenza viruses in humans, and our limited data indicate that this might be a useful strategy for filovirus vaccines as well. Several of our antibodies showed protective efficacy when tested in a novel murine challenge model and may be developed into future therapeutics.
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- 2017
14. Ebola virus infection kinetics in chimeric mice reveal a key role of T cells as barriers for virus dissemination
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César Muñoz-Fontela, Estefanía Rodríguez, Stephanie Wurr, David M. Wozniak, Stephan Günther, Susanne Krasemann, Lisa Oestereich, Paula Ruibal, Sabrina Bockholt, Juliana Idoyaga, Anja Lüdtke, Xiangguo Qiu, Elisa Pallasch, Sergio Gómez-Medina, and Gary P. Kobinger
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0301 basic medicine ,Lymphoid Tissue ,T-Lymphocytes ,viruses ,Viremia ,Biology ,Virus Replication ,medicine.disease_cause ,Article ,Virus ,03 medical and health sciences ,Cross-Priming ,Antigen ,Antigens, CD ,Immunity ,Viral entry ,medicine ,Animals ,Mice, Knockout ,CD11b Antigen ,Multidisciplinary ,Ebola virus ,Dendritic Cells ,Hemorrhagic Fever, Ebola ,Ebolavirus ,medicine.disease ,Virology ,Mice, Inbred C57BL ,Kinetics ,030104 developmental biology ,Viral replication ,Host-Pathogen Interactions ,Immunology ,Integrin alpha Chains ,CD8 - Abstract
Ebola virus (EBOV) causes severe systemic disease in humans and non-human primates characterized by high levels of viremia and virus titers in peripheral organs. The natural portals of virus entry are the mucosal surfaces and the skin where macrophages and dendritic cells (DCs) are primary EBOV targets. Due to the migratory properties of DCs, EBOV infection of these cells has been proposed as a necessary step for virus dissemination via draining lymph nodes and blood. Here we utilize chimeric mice with competent hematopoietic-driven immunity, to show that EBOV primarily infects CD11b+ DCs in non-lymphoid and lymphoid tissues, but spares the main cross-presenting CD103+ DC subset. Furthermore, depletion of CD8 and CD4 T cells resulted in loss of early control of virus replication, viremia and fatal Ebola virus disease (EVD). Thus, our findings point out at T cell function as a key determinant of EVD progress and outcome.
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- 2017
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15. Mucosal Polyinosinic-Polycytidylic Acid Improves Protection Elicited by Replicating Influenza Vaccines via Enhanced Dendritic Cell Function and T Cell Immunity
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Paula Ruibal, Randy A. Albrecht, José Vicente Pérez-Girón, Anja Lüdtke, Jazmina L. G. Cruz, César Muñoz-Fontela, Alan Belicha-Villanueva, Sergio Gómez-Medina, Ebrahim Hassan, and Adolfo García-Sastre
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medicine.medical_treatment ,T cell ,Immunology ,Priming (immunology) ,Dendritic cell ,Biology ,Virology ,Vaccination ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Immunity ,Polyinosinic:polycytidylic acid ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Adjuvant - Abstract
Live-attenuated influenza vaccines (LAIVs) have the potential to generate CD8 T cell immunity that may limit the virulence of an antigenically shifted influenza strain in a population lacking protective Abs. However, current LAIVs exert limited T cell immunity restricted to the vaccine strains. One approach to improve LAIV-induced T cell responses is the use of specific adjuvants to enhance T cell priming by respiratory dendritic cells, but this hypothesis has not been addressed. In this study, we assessed the effect of the TLR3 ligand polyinosinic-polycytidylic acid (poly IC) on CD8 T cell immunity and protection elicited by LAIVs. Mucosal treatment with poly IC shortly after vaccination enhanced respiratory dendritic cell function, CD8 T cell formation, and production of neutralizing Abs. This adjuvant effect of poly IC was dependent on amplification of TLR3 signaling by nonhematopoietic radioresistant cells and enhanced mouse protection to homosubtypic, as well as heterosubtypic, virus challenge. Our findings indicate that mucosal TLR3 ligation may be used to improve CD8 T cell responses to replicating vaccines, which has implications for protection in the absence of pre-existing Ab immunity.
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- 2014
16. Cytokine kinetics of Zika virus-infected patients from acute to reconvalescent phase
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Davis Fernandes Ferreira, José Vicente Pérez-Girón, Sergio Gómez-Medina, Alessandro Bartoloni, Dennis Tappe, Thomas Jaenisch, Jürgen Rissland, Stephan Günther, César Muñoz-Fontela, Jonas Schmidt-Chanasit, and Lorenzo Zammarchi
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0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,Asia ,Time Factors ,Immunology ,Disease ,Pacific Islands ,Arbovirus ,Zika virus ,Dengue fever ,Pathogenesis ,03 medical and health sciences ,Medical microbiology ,medicine ,Immunology and Allergy ,Humans ,Cytokine ,Travel ,biology ,business.industry ,Zika Virus Infection ,Flavivirus ,Outbreak ,General Medicine ,T-Lymphocytes, Helper-Inducer ,Middle Aged ,biology.organism_classification ,medicine.disease ,Virology ,030104 developmental biology ,Zika fever ,Cytokines ,Female ,business ,Brazil ,Rapid Communication - Abstract
Zika virus is an emerging mosquito-borne flavivirus currently causing large epidemics in the Pacific Ocean region and Brazil. Clinically, Zika fever resembles dengue fever, but is less severe. Whereas the clinical syndrome and laboratory diagnostic procedures have been described, little attention was paid to the immunology of the disease and its possible use for clinical follow-up of patients. Here, we investigate the role of cytokines in the pathogenesis of Zika fever in travelers returning from Asia, the Pacific, and Brazil. Polyfunctional T cell activation (Th1, Th2, Th9, and Th17 response) was seen during the acute phase characterized by respective cytokine level increases, followed by a decrease in the reconvalescent phase.
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- 2015
17. Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
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Sergio Gómez-Medina, Anja Lüdtke, José Vicente Pérez-Girón, and César Muñoz-Fontela
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Influenza vaccine ,General Chemical Engineering ,T-Lymphocytes ,Immunology ,Biology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Influenza A Virus, H2N2 Subtype ,Mice ,Immune system ,Influenza A Virus, H1N1 Subtype ,Immunity ,medicine ,Influenza A virus ,Live attenuated influenza vaccine ,Animals ,Humans ,Immunity, Mucosal ,Vaccines, Synthetic ,Ebola virus ,General Immunology and Microbiology ,Chimera ,General Neuroscience ,Dendritic Cells ,Acquired immune system ,Virology ,Vaccination ,Mice, Inbred C57BL ,HEK293 Cells ,Influenza Vaccines ,Female - Abstract
Vaccines are one of the greatest achievements of mankind, and have saved millions of lives over the last century. Paradoxically, little is known about the physiological mechanisms that mediate immune responses to vaccines perhaps due to the overall success of vaccination, which has reduced interest into the molecular and physiological mechanisms of vaccine immunity. However, several important human pathogens including influenza virus still pose a challenge for vaccination, and may benefit from immune-based strategies. Although influenza reverse genetics has been successfully applied to the generation of live-attenuated influenza vaccines (LAIVs), the addition of molecular tools in vaccine preparations such as tracer components to follow up the kinetics of vaccination in vivo, has not been addressed. In addition, the recent generation of mouse models that allow specific depletion of leukocytes during kinetic studies has opened a window of opportunity to understand the basic immune mechanisms underlying vaccine-elicited protection. Here, we describe how the combination of reverse genetics and chimeric mouse models may help to provide new insights into how vaccines work at physiological and molecular levels, using as example a recombinant, cold-adapted, live-attenuated influenza vaccine (LAIV). We utilized laboratory-generated LAIVs harboring cell tracers as well as competitive bone marrow chimeras (BMCs) to determine the early kinetics of vaccine immunity and the main physiological mechanisms responsible for the initiation of vaccine-specific adaptive immunity. In addition, we show how this technique may facilitate gene function studies in single animals during immune responses to vaccines. We propose that this technique can be applied to improve current prophylactic strategies against pathogens for which urgent medical countermeasures are needed, for example influenza, HIV, Plasmodium, and hemorrhagic fever viruses such as Ebola virus.
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- 2015
18. P114 Modulation of vaccine-induced T cell immunity by specific adjuvants
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Sergio Gómez-Medina, V. Perez-Giron, Cesar Munoz-Fontela, Alan Belicha-Villanueva, Jazmina Gonzalez-Cruz, Stefanie Ahrens, and Adolfo García-Sastre
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biology ,T cell ,Immunology ,Hematology ,Acquired immune system ,Biochemistry ,Virology ,Vaccination ,Immune system ,medicine.anatomical_structure ,Interferon ,biology.protein ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Molecular Biology ,Neuraminidase ,CD8 ,medicine.drug - Abstract
Introduction Successful vaccination requires generation of long-lasting and protective T cell responses, and thus, therapeutic strategies aimed to enhance vaccine-induced T cell immunity are a source of great interest. Here we have investigated the influence of toll-like receptor (TLR)-3 ligands as well as type I interferon (IFN) agonists on the maintenance of CD8 + T cell memory in the context of mucosal influenza vaccination. Methods Mice and vaccine studies. C57BL/6 J male mice between 8–10 weeks of age were used for our studies. Cold-adapted influenza vaccines were rescued by reverse genetics using A/Puerto Rico/8/34 (H1N1) hemagglutinin (HA) and neuraminidase (NA) segments in a A/Ann Arbor/6/60/ (H2N2) background (6 + 2 reassortant). Recombinant viruses were grown at 33 °C in 9-days old chicken eggs and titrated in Madin-Darby canine kidney cells (MDCKs) as described elsewhere. Nutlin-3 was purchased from Cayman Chemicals, poly I:C was purchased from Invivogen. Combinations of vaccine + adjuvants were administered intranasally in a maximum volume of 50 ml. Tissue samples were harvested from euthanized mice and processed for analysis of viral titers, quantitative RT-PCR, or ELISA. In survival experiments mice were sacrificed if their weight dropped more than 25% of their initial body weight as per institutional guidelines. The animal experiments were performed according to the guidelines of the German animal protection law. All animal protocols were approved by the relevant German authorities. Flow cytometry. Lung samples were enzymatically digested with 2 mg/ml of Collagenase D (Roche). Mediastinal lymph nodes were disrupted mechanically. Tissue samples were processed for flow cytometry and red cells were lysed using BD Red Blood Cell Lysing Buffer. Samples were acquired on a FACS canto II instrument and analyzed with FlowJO software (Treestar). Results Engagement of TLR3 and type I IFN signaling by candidate adjuvants of cold-adapted influenza vaccines in mice, increased vaccine-induced cytokine production early after mucosal administration, including enhanced production of MCP1, IP-10 and G-CSF. This increase in vaccine-induced early inflammatory responses resulted in robust cytotoxic T lymphocyte (CTL) activity, rapid viral clearance, and enhanced survival to influenza challenge. Conversely, vaccine adjuvants did not influence antibody titers in vaccinated individuals, suggesting that the early events that take place during the innate phase of the immune response play a chief role on the establishment and modulation of adaptive immunity. Conclusion Our results indicated that specific adjuvants with the ability to enhance TLR3 and type I IFN signaling enhance cytokine responses associated to vaccine administration, which resulted in improved CD8 + T cell-dependent recall responses. Of note, adjuvant-vaccine regimens reduced the vaccine dose necessary to provide protection to lethal challenge. These findings indicate that modulation of innate immunity via TLR ligands and type I IFN agonists may serve as a therapeutic strategy to enhance T cell memory maintenance after influenza vaccination, and may provide means to reduce the amount of vaccine stock necessary to protect individuals at risk in the face of an influenza pandemic.
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- 2012
19. Chikungunya Outbreak in the Republic of the Congo, 2019—Epidemiological, Virological and Entomological Findings of a South-North Multidisciplinary Taskforce Investigation
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Francesco Vairo, Martin Parfait Aimè Coussoud-Mavoungou, Francine Ntoumi, Concetta Castilletti, Lambert Kitembo, Najmul Haider, Fabrizio Carletti, Francesca Colavita, Cesare E. M. Gruber, Marco Iannetta, Francesco Messina, Simone Lanini, Biez Ulrich Judicaël, Emanuela Giombini, Chiara Montaldo, Chantal Portella, Steve Diafouka-Diatela, Martina Rueca, Richard Kock, Barbara Bartolini, Leonard Mboera, Vincent Munster, Robert Fischer, Stephanie Seifert, César Muñoz-Fontela, Beatriz Escudero-Pérez, Sergio Gomez-Medina, Emily V. Nelson, Patrick Kjia Tungu, Emanuele Nicastri, Vincenzo Puro, Antonino Di Caro, Maria Rosaria Capobianchi, Jacqueline Lydia Mikolo, Alimuddin Zumla, Giuseppe Ippolito, and on behalf of the Pandora-ID-NET Consortium Chikungunya Outbreak Group Taskforce
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chikungunya ,Republic of Congo ,outbreak ,Aedes spp ,mosquito ,arbovirus ,Microbiology ,QR1-502 - Abstract
The Republic of Congo (RoC) declared a chikungunya (CHIK) outbreak on 9 February 2019. We conducted a ONE-Human-Animal HEALTH epidemiological, virological and entomological investigation. Methods: We collected national surveillance and epidemiological data. CHIK diagnosis was based on RT-PCR and CHIKV-specific antibodies. Full CHIKV genome sequences were obtained by Sanger and MinION approaches and Bayesian tree phylogenetic analysis was performed. Mosquito larvae and 215 adult mosquitoes were collected in different villages of Kouilou and Pointe-Noire districts and estimates of Aedes (Ae.) mosquitos’ CHIKV-infectious bites obtained. We found two new CHIKV sequences of the East/Central/South African (ECSA) lineage, clustering with the recent enzootic sub-clade 2, showing the A226V mutation. The RoC 2019 CHIKV strain has two novel mutations, E2-T126M and E2-H351N. Phylogenetic suggests a common origin from 2016 Angola strain, from which it diverged around 1989 (95% HPD 1985–1994). The infectious bite pattern was similar for 2017, 2018 and early 2019. One Ae. albopictus pool was RT-PCR positive. The 2019 RoC CHIKV strain seems to be recently introduced or be endemic in sylvatic cycle. Distinct from the contemporary Indian CHIKV isolates and in contrast to the original Central-African strains (transmitted by Ae. aegypti), it carries the A226V mutation, indicating an independent adaptive mutation in response to vector replacement (Ae. albopictus vs Ae. aegypti).
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- 2020
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20. Ebola Virus Disease Survivors Show More Efficient Antibody Immunity than Vaccinees Despite Similar Levels of Circulating Immunoglobulins
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Till Koch, Monika Rottstegge, Paula Ruibal, Sergio Gomez-Medina, Emily V. Nelson, Beatriz Escudero-Pérez, Matthias Pillny, My Linh Ly, Fara Raymond Koundouno, Joseph Akoi Bore, N’Faly Magassouba, Christine Dahlke, Stephan Günther, Miles W. Carroll, Marylyn M. Addo, and César Muñoz-Fontela
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Ebola virus ,VSV ,vaccine ,antibodies ,immune memory ,Microbiology ,QR1-502 - Abstract
The last seven years have seen the greatest surge of Ebola virus disease (EVD) cases in equatorial Africa, including the 2013–2016 epidemic in West Africa and the recent epidemics in the Democratic Republic of Congo (DRC). The vaccine clinical trials that took place in West Africa and the DRC, as well as follow-up studies in collaboration with EVD survivor communities, have for the first time allowed researchers to compare immune memory induced by natural infection and vaccination. These comparisons may be relevant to evaluate the putative effectiveness of vaccines and candidate medical countermeasures such as convalescent plasma transfer. In this study, we compared the long-term functionality of anti-EBOV glycoprotein (GP) antibodies from EVD survivors with that from volunteers who received the recombinant vesicular stomatitis virus vectored vaccine (rVSV-ZEBOV) during the Phase I clinical trial in Hamburg. Our study highlights important differences between EBOV vaccination and natural infection and provides a framework for comparison with other vaccine candidates.
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- 2020
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