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Nature Reviews. Microbiology Feb 2023Lassa virus (LASV) is endemic in the rodent populations of Sierra Leone, Nigeria and other countries in West Africa. Spillover to humans occurs frequently and results in... (Review)
Review
Lassa virus (LASV) is endemic in the rodent populations of Sierra Leone, Nigeria and other countries in West Africa. Spillover to humans occurs frequently and results in Lassa fever, a viral haemorrhagic fever (VHF) associated with a high case fatality rate. Despite advances, fundamental gaps in knowledge of the immunology, epidemiology, ecology and pathogenesis of Lassa fever persist. More frequent outbreaks, the potential for further geographic expansion of Mastomys natalensis and other rodent reservoirs, the ease of procurement and possible use and weaponization of LASV, the frequent importation of LASV to North America and Europe, and the emergence of novel LASV strains in densely populated West Africa have driven new initiatives to develop countermeasures for LASV. Although promising candidates are being evaluated, as yet there are no approved vaccines or therapeutics for human use. This Review discusses the virology of LASV, the clinical course of Lassa fever and the progress towards developing medical countermeasures.
Topics: Humans; Lassa Fever; Lassa virus; Africa, Western; Viral Vaccines
PubMed: 36097163
DOI: 10.1038/s41579-022-00789-8 -
Cell Host & Microbe Dec 2022The Lassa virus is endemic in parts of West Africa, and it causes hemorrhagic fever with high mortality. The development of a recombinant protein vaccine has been...
The Lassa virus is endemic in parts of West Africa, and it causes hemorrhagic fever with high mortality. The development of a recombinant protein vaccine has been hampered by the instability of soluble Lassa virus glycoprotein complex (GPC) trimers, which disassemble into monomeric subunits after expression. Here, we use two-component protein nanoparticles consisting of trimeric and pentameric subunits to stabilize GPC in a trimeric conformation. These GPC nanoparticles present twenty prefusion GPC trimers on the surface of an icosahedral particle. Cryo-EM studies of GPC nanoparticles demonstrated a well-ordered structure and yielded a high-resolution structure of an unliganded GPC. These nanoparticles induced potent humoral immune responses in rabbits and protective immunity against the lethal Lassa virus challenge in guinea pigs. Additionally, we isolated a neutralizing antibody that mapped to the putative receptor-binding site, revealing a previously undefined site of vulnerability. Collectively, these findings offer potential approaches to vaccine and therapeutic design for the Lassa virus.
Topics: Guinea Pigs; Rabbits; Animals; Lassa virus; Antibodies, Neutralizing; Lassa Fever; Glycoproteins; Vaccines, Synthetic; Nanoparticles
PubMed: 36400021
DOI: 10.1016/j.chom.2022.10.018 -
International Journal of Infectious... Jun 2022This summary on Lassa virus (LASV) infection and Lassa fever disease (LF) was developed from a clinical perspective to provide clinicians with a condensed, accessible... (Review)
Review
OBJECTIVES
This summary on Lassa virus (LASV) infection and Lassa fever disease (LF) was developed from a clinical perspective to provide clinicians with a condensed, accessible understanding of the current literature. The information provided highlights pathogenesis, clinical features, and diagnostics emphasizing therapies and vaccines that have demonstrated potential value for use in clinical or research environments.
METHODS
We conducted an integrative literature review on the clinical and pathological features, vaccines, and treatments for LASV infection, focusing on recent studies and in vivo evidence from humans and/or non-human primates (NHPs), when available.
RESULTS
Two antiviral medications with potential benefit for the treatment of LASV infection and 1 for post-exposure prophylaxis were identified, although a larger number of therapeutic candidates are currently being evaluated. Multiple vaccine platforms are in pre-clinical development for LASV prevention, but data from human clinical trials are not yet available.
CONCLUSION
We provide succinct summaries of medical countermeasures against LASV to give the busy clinician a rapid reference. Although there are no approved drugs or vaccines for LF, we provide condensed information from a literature review for measures that can be taken when faced with a suspected infection, including investigational treatment options and hospital engineering controls.
Topics: Animals; Antiviral Agents; Humans; Lassa Fever; Lassa virus; Viral Vaccines
PubMed: 35395384
DOI: 10.1016/j.ijid.2022.04.004 -
F1000Research 2019Lassa virus (LASV) is a highly prevalent mammarenavirus in West Africa and is maintained in nature in a persistently infected rodent host, , which is widely spread in... (Review)
Review
Lassa virus (LASV) is a highly prevalent mammarenavirus in West Africa and is maintained in nature in a persistently infected rodent host, , which is widely spread in sub-Saharan Africa. LASV infection of humans can cause Lassa fever (LF), a disease associated with high morbidity and significant mortality. Recent evidence indicates an LASV expansion outside its traditional endemic areas. In 2017, the World Health Organization (WHO) included LASV in top-priority pathogens and released a Target Product Profile (TPP) for vaccine development. Likewise, in 2018, the US Food and Drug Administration added LF to a priority review voucher program to encourage the development of preventive and therapeutics measures. In this article, we review recent progress in LASV vaccine research and development with a focus on the impact of LASV genetic and biological diversity on the design and development of vaccine candidates meeting the WHO's TPP for an LASV vaccine.
Topics: Africa, Western; Animals; Humans; Lassa Fever; Lassa virus; Murinae; Viral Vaccines
PubMed: 30774934
DOI: 10.12688/f1000research.16989.1 -
Cell Reports May 2023Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for...
Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines.
Topics: Humans; Lassa virus; Antibodies, Neutralizing; Lassa Fever; Glycoproteins; Antigens, Viral
PubMed: 37209096
DOI: 10.1016/j.celrep.2023.112524 -
Journal of Clinical Microbiology Jun 2017Lassa virus remains an important cause of illness in West Africa and among the travelers returning from this region with an acute febrile illness. The symptoms of Lassa... (Review)
Review
Lassa virus remains an important cause of illness in West Africa and among the travelers returning from this region with an acute febrile illness. The symptoms of Lassa fever can be nonspecific and mimic those of other endemic infections, especially early in illness, making a clinical diagnosis difficult; therefore, laboratory testing is needed to confirm the diagnosis. An early identification of Lassa fever is crucial for maximizing the benefit of available antiviral therapy, as treatment efficacy rapidly decreases following the clinical onset of the disease. This minireview provides an overview of the currently available diagnostic tests for Lassa fever and their strengths and weaknesses.
Topics: Africa, Western; Clinical Laboratory Techniques; Diagnostic Tests, Routine; Humans; Lassa Fever; Lassa virus
PubMed: 28404674
DOI: 10.1128/JCM.00170-17 -
Biotechnology and Bioengineering Mar 2021Lack of experimental human models hinders research on Lassa hemorrhagic fever and the development of treatment strategies. Here, we report the first chip-based model for...
Lack of experimental human models hinders research on Lassa hemorrhagic fever and the development of treatment strategies. Here, we report the first chip-based model for Lassa hemorrhagic syndrome. The chip features a microvessel interfacing collagen network as a simple mimic for extracellular matrix, allowing for quantitative and real-time vascular integrity assessment. Luminal infusion of Lassa virus-like particles led to a dramatic increase in vascular permeability in a viral load-dependent manner. Using this platform, we showed that Fibrin-derived peptide FX06 can be used to suppress the vascular integrity loss. This simple chip-based model proved promising in the assessment of disease severity and provides an easy-to-use platform for future investigation of Lassa pathogenesis and drug development in a human-like setting.
Topics: Human Umbilical Vein Endothelial Cells; Humans; Lab-On-A-Chip Devices; Lassa Fever; Lassa virus; Microfluidic Analytical Techniques; Models, Biological; Shock, Hemorrhagic; Syndrome
PubMed: 33241859
DOI: 10.1002/bit.27636 -
Current Opinion in Virology Aug 2019Lassa fever is a unique viral hemorrhagic fever that is endemic in parts of West Africa, primarily Sierra Leone, Guinea, Liberia, and Nigeria. The disease is caused by... (Review)
Review
Lassa fever is a unique viral hemorrhagic fever that is endemic in parts of West Africa, primarily Sierra Leone, Guinea, Liberia, and Nigeria. The disease is caused by the Lassa virus, an Old World arenavirus that has as primary reservoir host the multimammate rodent Mastomys nataliensis, which lives in association with humans. Recent estimates suggest LF causes two million cases and 5000-10000 deaths annually, mainly in West Africa. Clinical diagnosis and laboratory confirmation have always been major challenges for effective management and control of the disease in afflicted areas of West Africa. Recent advancements in molecular biology, recombinant DNA technology, and genomics sequencing has facilitated major advancement in development of better diagnostic and surveillance tools for Lassa fever virus. These include, the multiplex, magnetic bead-based immunodiagnostics for both Lassa virus antigens and antibodies; molecular probe-based quantitative real-time PCR for genomic signatures; rapid diagnostics tests that detects the most prevalent West African lineages; and the successful utilization of next-generation sequencing technology to diagnose and characterize Lassa virus in West Africa. These advances will continue to improve disease treatment, control, and prevention. In this review we will discuss progression of Lassa virus diagnostics from the past and into the future.
Topics: Africa, Western; Antigens, Viral; Clinical Laboratory Techniques; Genomics; Humans; Lassa Fever; Lassa virus; Molecular Diagnostic Techniques; Serologic Tests
PubMed: 31518896
DOI: 10.1016/j.coviro.2019.08.002 -
Emerging Infectious Diseases Nov 2023Lassa fever, caused by Lassa virus (LASV), is endemic to West Africa, where ≈300,000 illnesses and ≈5,000 deaths occur annually. LASV is primarily spread by infected...
Lassa fever, caused by Lassa virus (LASV), is endemic to West Africa, where ≈300,000 illnesses and ≈5,000 deaths occur annually. LASV is primarily spread by infected multimammate rats via urine and fomites, highlighting the need to understand the environmental fate of LASV. We evaluated persistence of LASV Josiah and Sauerwald strains on surfaces, in aqueous solutions, and with sodium hypochlorite disinfection. Tested strains were more stable in deionized water (first-order rate constant [k] for Josiah, 0.23 days; for Sauerwald, k = 0.34 days) than primary influent wastewater (Josiah, k = 1.3 days; Sauerwald, k = 1.9 days). Both strains had similar decay rates on high-density polyethylene (Josiah, k = 4.3 days; Sauerwald, k = 2.3 days) and stainless steel (Josiah, k = 5.3 days; Sauerwald, k = 2.7 days). Sodium hypochlorite was highly effective at inactivating both strains. Our findings can inform future risk assessment and management efforts for Lassa fever.
Topics: Animals; Rats; Lassa virus; Lassa Fever; Disinfection; Sodium Hypochlorite; Africa, Western
PubMed: 37877545
DOI: 10.3201/eid2911.230678 -
Viruses Oct 2012Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000... (Review)
Review
Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host's immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Genome, Viral; Humans; Immune Evasion; Lassa Fever; Lassa virus; Liver; Necrosis; Viral Load; Viremia; Virus Replication
PubMed: 23202452
DOI: 10.3390/v4102031