#Junin Virus Triggers #Macrophage Activation and Modulates Polarization According to Viral Strain #Pathogenicity (Front Immunol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Front Immunol. 2019 Oct 22;10:2499. doi: 10.3389/fimmu.2019.02499. eCollection 2019.

Junin Virus Triggers Macrophage Activation and Modulates Polarization According to Viral Strain Pathogenicity.

Ferrer MF1, Thomas P1, López Ortiz AO1,2, Errasti AE3, Charo N2, Romanowski V1,4, Gorgojo J5, Rodriguez ME5, Carrera Silva EA2, Gómez RM1,4.

Author information: 1 Laboratorio de Virus Animales, Instituto de Biotecnología y Biología Molecular, CONICET-Universidad Nacional de La Plata, La Plata, Argentina. 2 Laboratorio de Trombosis Experimental, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina. 3 Facultad de Medicina, Instituto de Farmacologia, University of Buenos Aries, Buenos Aires, Argentina. 4 Global Viral Network, Baltimore, MD, United States. 5 Centro de Investigación y Desarrollo en Fermentaciones Industriales, CONICET-Universidad Nacional de La Plata, La Plata, Argentina.

 

Abstract

The New World arenavirus Junin (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF). Previous studies of human macrophage infection by the Old-World arenaviruses Mopeia and Lassa showed that while the non-pathogenic Mopeia virus replicates and activates human macrophages, the pathogenic Lassa virus replicates but fails to activate human macrophages. Less is known in regard to the impact of New World arenavirus infection on the human macrophage immune response. Macrophage activation is critical for controlling infections but could also be usurped favoring immune evasion. Therefore, it is crucial to understand how the JUNV infection modulates macrophage plasticity to clarify its role in AHF pathogenesis. With this aim in mind, we compared infection with the attenuated Candid 1 (C#1) or the pathogenic P strains of the JUNV virus in human macrophage cultures. The results showed that both JUNV strains similarly replicated and induced morphological changes as early as 1 day post-infection. However, both strains differentially induced the expression of CD71, the receptor for cell entry, the activation and maturation molecules CD80, CD86, and HLA-DR and selectively modulated cytokine production. Higher levels of TNF-α, IL-10, and IL-12 were detected with C#1 strain, while the P strain induced only higher levels of IL-6. We also found that C#1 strain infection skewed macrophage polarization to M1, whereas the P strain shifted the response to an M2 phenotype. Interestingly, the MERTK receptor, that negatively regulates the immune response, was down-regulated by C#1 strain and up-regulated by P strain infection. Similarly, the target genes of MERTK activation, the cytokine suppressors SOCS1 and SOCS3, were also increased after P strain infection, in addition to IRF-1, that regulates type I IFN levels, which were higher with C#1 compared with P strain infection. Together, this differential activation/polarization pattern of macrophages elicited by P strain suggests a more evasive immune response and may have important implications in the pathogenesis of AHF and underpinning the development of new potential therapeutic strategies.

Copyright © 2019 Ferrer, Thomas, López Ortiz, Errasti, Charo, Romanowski, Gorgojo, Rodriguez, Carrera Silva and Gómez.

KEYWORDS: IFN-I; TAM receptors; human macrophages; junin virus; macrophage activation; macrophage polarization

PMID: 31695702 PMCID: PMC6817498 DOI: 10.3389/fimmu.2019.02499

Keywords: Arenavirus; Junin virus; Argentine Hemorrhagic Fever; Mopeia virus; Lassa fever virus; Viral pathogenesis.

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#Lassa Fever: #Epidemiology, #Clinical Features, #Diagnosis, #Management and Prevention (Infect Dis Clin North Am., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Infect Dis Clin North Am. 2019 Dec;33(4):933-951. doi: 10.1016/j.idc.2019.08.002.

Lassa Fever: Epidemiology, Clinical Features, Diagnosis, Management and Prevention.

Asogun DA1, Günther S2, Akpede GO3, Ihekweazu C4, Zumla A5.

Author information: 1 Department of Public Health, College of Medicine, Ambrose Alli University, Ekpoma, Nigeria; Department of Public Health, Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, P.M.B 008, Kilometre 87, Benin City-Auchi Road, Irrua, Nigeria. Electronic address: asogun2001@yahoo.com. 2 Bernhard-Nocht Institute for Tropical Medicine, Strab 74, Hamburg 20359, Germany; German Centre for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany. 3 Department of Paediatrics, Faculty of Clinical Sciences, College of Medicine, Ambrose Alli University, Ekpoma, Nigeria. 4 Nigeria Centre for Disease Control, Plot 801, Ebitu Ukiwe Street, Jabi, Abuja, Nigeria. 5 Center for Clinical Microbiology, University College London, Royal Free Campus 2nd Floor, Rowland Hill Street, London NW3 2PF, United Kingdom.

 

Abstract

Lassa fever outbreaks West Africa have caused up to 10,000 deaths annually. Primary infection occurs from contact with Lassa virus-infected rodents and exposure to their excreta, blood, or meat. Incubation takes 2 to 21 days. Symptoms are difficult to distinguish from malaria, typhoid, dengue, yellow fever, and other viral hemorrhagic fevers. Clinical manifestations range from asymptomatic, to mild, to severe fulminant disease. Ribavirin can improve outcomes. Overall mortality is between 1% and 15%. Lassa fever should be considered in the differential diagnosis with travel to West Africa. There is an urgent need for rapid field-friendly diagnostics and preventive vaccine.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS: Clinical features; Diagnosis; Epidemic; Epidemiology; Lassa fever; Nosocomial transmission; Prevention; Rodents

PMID: 31668199 DOI: 10.1016/j.idc.2019.08.002

_

Keywords: Lassa fever.

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#Lassa virus circulating in #Liberia: a retrospective #genomic characterisation (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Lassa virus circulating in Liberia: a retrospective genomic characterisation

Michael R Wiley, PhD *, Lawrence Fakoli, BSc *, Andrew G Letizia, MD *, Stephen R Welch, PhD *, Jason T Ladner, PhD *, Karla Prieto, MSc, Daniel Reyes, MSc, Nicole Espy, PhD, Joseph A Chitty, BSc, Catherine B Pratt, MSc, Nicholas Di Paola, ScD, Fahn Taweh, MPH, Desmond Williams, MD, Jon Saindon, PhD, William G Davis, PhD, Ketan Patel, PhD, Mitchell Holland, MS, Daniel Negrón, MS, Ute Ströher, PhD, Stuart T Nichol, PhD, Shanmuga Sozhamannan, PhD, Pierre E Rollin, MD, John Dogba, MPH, Tolbert Nyenswah, MPH, Fatorma Bolay, PhD, César G Albariño, PhD †, Mosoka Fallah, MD †, Gustavo Palacios, PhD  †

Published: October 03, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30486-4

 

Summary

Background

An alarming rise in reported Lassa fever cases continues in west Africa. Liberia has the largest reported per capita incidence of Lassa fever cases in the region, but genomic information on the circulating strains is scarce. The aim of this study was to substantially increase the available pool of data to help foster the generation of targeted diagnostics and therapeutics.

Methods

Clinical serum samples collected from 17 positive Lassa fever cases originating from Liberia (16 cases) and Guinea (one case) within the past decade were processed at the Liberian Institute for Biomedical Research using a targeted-enrichment sequencing approach, producing 17 near-complete genomes. An additional 17 Lassa virus sequences (two from Guinea, seven from Liberia, four from Nigeria, and four from Sierra Leone) were generated from viral stocks at the US Centers for Disease Control and Prevention (Atlanta, GA) from samples originating from the Mano River Union (Guinea, Liberia, and Sierra Leone) region and Nigeria. Sequences were compared with existing Lassa virus genomes and published Lassa virus assays.

Findings

The 23 new Liberian Lassa virus genomes grouped within two clades (IV.A and IV.B) and were genetically divergent from those circulating elsewhere in west Africa. A time-calibrated phylogeographic analysis incorporating the new genomes suggests Liberia was the entry point of Lassa virus into the Mano River Union region and estimates the introduction to have occurred between 300–350 years ago. A high level of diversity exists between the Liberian Lassa virus genomes. Nucleotide percent difference between Liberian Lassa virus genomes ranged up to 27% in the L segment and 18% in the S segment. The commonly used Lassa Josiah-MGB assay was up to 25% divergent across the target sites when aligned to the Liberian Lassa virus genomes.

Interpretation

The large amount of novel genomic diversity of Lassa virus observed in the Liberian cases emphasises the need to match deployed diagnostic capabilities with locally circulating strains and underscores the importance of evaluating cross-lineage protection in the development of vaccines and therapeutics.

Funding

Defense Biological Product Assurance Office of the US Department of Defense and the Armed Forces Health Surveillance Branch and its Global Emerging Infections Surveillance and Response Section.

Keywords: Lassa fever; Liberia.

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#Vaccines inducing #immunity to #Lassa virus glycoprotein and nucleoprotein protect #macaques after a single shot (Sci Transl Med., abstract)

[Source: Science Translational Medicine, full page: (LINK). Abstract, edited.]

Vaccines inducing immunity to Lassa virus glycoprotein and nucleoprotein protect macaques after a single shot

Mathieu Mateo1,2, Stéphanie Reynard1,2, Xavier Carnec1,2, Alexandra Journeaux1,2, Nicolas Baillet1,2, Justine Schaeffer1,2, Caroline Picard1,2, Catherine Legras-Lachuer3, Richard Allan3, Emeline Perthame4, Kenzo-Hugo Hillion4, Natalia Pietrosemoli4, Marie-Agnès Dillies4, Laura Barrot5, Audrey Vallve5, Stéphane Barron5, Lyne Fellmann6, Jean-Charles Gaillard7, Jean Armengaud7, Caroline Carbonnelle5, Hervé Raoul5, Frédéric Tangy8 and Sylvain Baize1,2,*

1 Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, Lyon, France. 2 Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, INSERM U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, CNRS UMR5308, Lyon, France. 3 ViroScan3D SAS, Trévoux, France. 4 Bioinformatics and Biostatistics Hub–Department of Computational Biology, USR 3756 CNRS, Institut Pasteur, Paris, France. 5 Laboratoire P4 INSERM–Jean Mérieux, INSERM US003, Lyon, France. 6 SILABE, Université de Strasbourg, Fort Foch, Niederhausbergen, France. 7 Laboratoire Innovations Technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Commissariat à l’Energie Atomique, Bagnols-sur-Cèze, France. 8 Viral Genomics and Vaccination, Institut Pasteur, CNRS UMR-3569, Paris, France.

*Corresponding author. Email: sylvain.baize@pasteur.fr

Science Translational Medicine  02 Oct 2019: Vol. 11, Issue 512, eaaw3163 / DOI: 10.1126/scitranslmed.aaw3163

 

A vaccine to fight Lassa fever

Thousands of people in Western Africa succumb to Lassa fever each year. Lassa virus infections can in some cases respond to antiviral treatment, but there is no vaccine. Mateo et al. tested three different viral-vectored Lassa virus vaccines in a nonhuman primate model. They compared transcriptomic and proteomic signatures as well as B cell and T cell responses after vaccination. One vaccine using a measles virus vector with Lassa virus glycoprotein and nucleoprotein provided almost sterilizing protection upon a lethal Lassa virus challenge. This vaccine will soon be tested in humans and has the potential to make a major impact on the incidence of Lassa fever.

 

Abstract

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.

Keywords: Lassa fever; Vaccines; Animal models.

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#Molecular confirmation and #phylogeny of #Lassa fever virus in #Benin Republic 2014-2016 (Afr J Lab Med., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Afr J Lab Med. 2019 Aug 22;8(1):803. doi: 10.4102/ajlm.v8i1.803. eCollection 2019.

Molecular confirmation and phylogeny of Lassa fever virus in Benin Republic 2014-2016.

Salu OB1,2, James AB2,3, Bankolé HS4,5, Agbla JM5, Da Silva M5, Gbaguidi F5,6, Loko CF7, Omilabu SA1,2.

Author information: 1 Department of Medical Microbiology and Parasitology, College of Medicine, University of Lagos, Lagos, Nigeria. 2 Centre for Human and Zoonotic Virology, Central Research Laboratory, College of Medicine, University of Lagos, Lagos, Nigeria. 3 Department of Biochemistry, College of Medicine, University of Lagos, Lagos, Nigeria. 4 Department of Applied Microbiology and Pharmacology of Natural Sciences, University of Abomey-Calavi, Abomey-Calavi, Benin, Benin. 5 National Laboratory of Public Health, Ministry of Health, Benin, Benin. 6 Department of Pharmacognosy and Pharmaceutical Organic Chemistry, University of Abomey-Calavi, Abomey-Calavi, Benin. 7 De la Pharmacie, du Medicament et des Explorations Diagnostiques, Ministére de la Santé, Cotonou, Benin.

 

Abstract

BACKGROUND:

The changing epidemiology of the Lassa virus from endemic areas to other parts of West Africa has been reported. However, there have been no documented Lassa fever transmission chains in the Benin Republic. Two outbreaks of Lassa fever (November 2014 and January 2016) in the Benin Republic were characterised by a high number of deaths (more than 50%) among 27 confirmed and other unconfirmed cases.

OBJECTIVES:

We report the detection, confirmation and relatedness of the Lassa virus strains from the Benin Republic with other isolates within the West African Sub-region.

METHODS:

A total of 70 blood samples (16 from 2014 and 54 from 2016) from suspected cases with signs and symptoms suggestive of viral haemorrhagic fever were received for molecular analysis at the Centre for Human and Zoonotic Virology, College of Medicine, University of Lagos and the Lagos University Teaching Hospital. With the detection of the Lassa virus RNA by reverse transcriptase polymerase chain reaction, sequencing and phylogenetic analyses were performed using the Sanger dideoxy sequencing technology platform and the MEGA6 software.

RESULTS:

S segments of the Lassa virus RNA genome were detected in 5 (7.1%) of the 70 samples analysed. Sequencing and a phylogenetic tree construction confirmed that the strain of Lassa virus had close relationships with strains previously isolated from Nigeria.

CONCLUSION:

We confirmed the presence of the Lassa virus in the Benin Republic, with 2 strains having molecular epidemiological links with Lineage I and II strains from Nigeria. To reduce the likelihood of outbreaks, there is a need for heightened awareness and strengthened surveillance systems about Lassa fever, particularly in the sub-region.

KEYWORDS: Benin Republic; Lassa virus; West Africa; phylogeny; surveillance

PMID: 31534915 PMCID: PMC6739551 DOI: 10.4102/ajlm.v8i1.803

Keywords: Lassa fever; Benin; Nigeria.

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A review of #Lassa fever #vaccine candidates (Curr Opin Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Curr Opin Virol. 2019 Aug 28;37:105-111. doi: 10.1016/j.coviro.2019.07.006. [Epub ahead of print]

A review of Lassa fever vaccine candidates.

Salami K1, Gouglas D2, Schmaljohn C3, Saville M4, Tornieporth N5.

Author information: 1 R & D Blueprint for the Prevention of Epidemics, Room 3170, World Health Organization Headquarters, 20, Avenue Appia, Geneva 1211, Switzerland. 2 Coalition for Epidemic Preparedness Innovations, Marcus Thranes Gate 2, 0473 Oslo, Norway. 3 U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Frederick, MD 21702, USA. 4 Coalition for Epidemic Preparedness Innovations, Gibbs Building, 215 Euston Rd, Bloomsbury, London NW1 2BE, UK. Electronic address: Melanie.saville@cepi.net. 5 Coalition for Epidemic Preparedness Innovations, Gibbs Building, 215 Euston Rd, Bloomsbury, London NW1 2BE, UK.

 

Abstract

Lassa fever is a zoonotic disease caused by the Lassa virus, a rodent-borne arenavirus endemic to West Africa. Recent steady increase in reported cases of the disease in Nigeria, where 123 deaths occurred in 546 confirmed cases in 2019 has further underlined the need to accelerate the development of vaccines for preventing the disease. Intensified research and development of Lassa fever medical countermeasures have yielded some vaccine candidates with preclinical scientific plausibility using predominantly novel technology. The more advanced candidates are based on recombinant measles, Vesicular Stomatitis Virus or Mopiea and Lassa virus reassortants expressing Lassa virus antigens, and the deoxyribonucleic acid platform. However, the Lassa fever portfolio still lags behind other neglected tropical diseases’, and further investments are needed for continued development and additional research, such as the safety and efficacy of these vaccine candidates in special populations.

Copyright © 2019. Published by Elsevier B.V.

PMID: 31472333 DOI: 10.1016/j.coviro.2019.07.006

Keywords:  Lassa fever, Vaccines.

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A Single Dose of Modified #Vaccinia Ankara Expressing #Lassa #VLPs Protects Mice from Lethal Intra- #cerebral Virus Challenge (Pathogens., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Pathogens. 2019 Aug 28;8(3). pii: E133. doi: 10.3390/pathogens8030133.

A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge.

Salvato MS1, Domi A2, Guzmán-Cardozo C1, Medina-Moreno S1, Zapata JC1, Hsu H1, McCurley N3, Basu R4, Hauser M2, Hellerstein M2, Guirakhoo F5.

Author information: 1 Institute of Human Virology, University of Maryland, Baltimore, MD 21201, USA. 2 GeoVax, Inc., Smyrna, GA 30080, USA. 3 Office of Technology Licensing and Commercialization, Georgia State University, Atlanta, GA 30303, USA. 4 Department of Biology, Georgia State University, Atlanta, GA 30302, USA. 5 GeoVax, Inc., Smyrna, GA 30080, USA. fguirakhoo@geovax.com.

 

Abstract

Lassa fever surpasses Ebola, Marburg, and all other hemorrhagic fevers except Dengue in its public health impact. Caused by Lassa virus (LASV), the disease is a scourge on populations in endemic areas of West Africa, where reported incidence is higher. Here, we report construction, characterization, and preclinical efficacy of a novel recombinant vaccine candidate GEO-LM01. Constructed in the Modified Vaccinia Ankara (MVA) vector, GEO-LM01 expresses the glycoprotein precursor (GPC) and zinc-binding matrix protein (Z) from the prototype Josiah strain lineage IV. When expressed together, GP and Z form Virus-Like Particles (VLPs) in cell culture. Immunogenicity and efficacy of GEO-LM01 was tested in a mouse challenge model. A single intramuscular dose of GEO-LM01 protected 100% of CBA/J mice challenged with a lethal dose of ML29, a Mopeia/Lassa reassortant virus, delivered directly into the brain. In contrast, all control animals died within one week. The vaccine induced low levels of antibodies but Lassa-specific CD4+ and CD8+ T cell responses. This is the first report showing that a single dose of a replication-deficient MVA vector can confer full protection against a lethal challenge with ML29 virus.

KEYWORDS: Lassa vaccine; VLP formation; cell-mediated immunity; replication-deficient MVA vector; single-dose efficacy

PMID: 31466243 DOI: 10.3390/pathogens8030133

Keywords: Lassa fever; Vaccines; Animal models.

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