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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 -
Cell Host & Microbe Jun 2023The COVID-19 pandemic galvanized the field of virus genomic surveillance, demonstrating its utility for public health. Now, we must harness the momentum that led to... (Review)
Review
The COVID-19 pandemic galvanized the field of virus genomic surveillance, demonstrating its utility for public health. Now, we must harness the momentum that led to increased infrastructure, training, and political will to build a sustainable global genomic surveillance network for other epidemic and endemic viruses. We suggest a generalizable modular sequencing framework wherein users can easily switch between virus targets to maximize cost-effectiveness and maintain readiness for new threats. We also highlight challenges associated with genomic surveillance and when global inequalities persist. We propose solutions to mitigate some of these issues, including training and multilateral partnerships. Exploring alternatives to clinical sequencing can also reduce the cost of surveillance programs. Finally, we discuss how establishing genomic surveillance would aid control programs and potentially provide a warning system for outbreaks, using a global respiratory virus (RSV), an arbovirus (dengue virus), and a regional zoonotic virus (Lassa virus) as examples.
Topics: Humans; COVID-19; Pandemics; Disease Outbreaks; Viruses; Public Health
PubMed: 36921604
DOI: 10.1016/j.chom.2023.03.003 -
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 -
Journal of Molecular Biology Aug 2023Although one member of the poxvirus family, variola virus, has caused one of the most devastating human infections worldwide, smallpox, the knowledge gained over the... (Review)
Review
Although one member of the poxvirus family, variola virus, has caused one of the most devastating human infections worldwide, smallpox, the knowledge gained over the last 30 years on the molecular, virological and immunological mechanisms of these viruses has allowed the use of members of this family as vectors for the generation of recombinant vaccines against numerous pathogens. In this review, we cover different aspects of the history and biology of poxviruses with emphasis on their application as vaccines, from first- to fourth-generation, against smallpox, monkeypox, emerging viral diseases highlighted by the World Health Organization (COVID-19, Crimean-Congo haemorrhagic fever, Ebola and Marburg virus diseases, Lassa fever, Middle East respiratory syndrome and severe acute respiratory syndrome, Nipah and other henipaviral diseases, Rift Valley fever and Zika), as well as against one of the most concerning prevalent virus, the Human Immunodeficiency Virus, the causative agent of Acquired Immunodeficiency Syndrome. We discuss the implications in human health of the 2022 monkeypox epidemic affecting many countries, and the rapid prophylactic and therapeutic measures adopted to control virus dissemination within the human population. We also describe the preclinical and clinical evaluation of the Modified Vaccinia virus Ankara and New York vaccinia virus poxviral strains expressing heterologous antigens from the viral diseases listed above. Finally, we report different approaches to improve the immunogenicity and efficacy of poxvirus-based vaccine candidates, such as deletion of immunomodulatory genes, insertion of host-range genes and enhanced transcription of foreign genes through modified viral promoters. Some future prospects are also highlighted.
Topics: Animals; Humans; Communicable Diseases, Emerging; COVID-19; Genetic Vectors; Mpox (monkeypox); Poxviridae; Smallpox; Vaccines, Attenuated; Vaccinia virus; Viral Vaccines; Virus Diseases; Zika Virus; Zika Virus Infection
PubMed: 37301278
DOI: 10.1016/j.jmb.2023.168173 -
Expert Review of Vaccines 2024
Topics: Humans; Vaccines; Virus Replication; Lassa virus; Lassa Fever; Arenaviridae Infections
PubMed: 38044877
DOI: 10.1080/14760584.2023.2290683 -
Cancer Gene Therapy Jun 2023Self-replicating RNA viruses have been engineered as efficient expression vectors for vaccine development for infectious diseases and cancers. Moreover, self-replicating... (Review)
Review
Self-replicating RNA viruses have been engineered as efficient expression vectors for vaccine development for infectious diseases and cancers. Moreover, self-replicating RNA viral vectors, particularly oncolytic viruses, have been applied for cancer therapy and immunotherapy. Among negative strand RNA viruses, measles viruses and rhabdoviruses have been frequently applied for vaccine development against viruses such as Chikungunya virus, Lassa virus, Ebola virus, influenza virus, HIV, Zika virus, and coronaviruses. Immunization of rodents and primates has elicited strong neutralizing antibody responses and provided protection against lethal challenges with pathogenic viruses. Several clinical trials have been conducted. Ervebo, a vaccine based on a vesicular stomatitis virus (VSV) vector has been approved for immunization of humans against Ebola virus. Different types of cancers such as brain, breast, cervical, lung, leukemia/lymphoma, ovarian, prostate, pancreatic, and melanoma, have been the targets for cancer vaccine development, cancer gene therapy, and cancer immunotherapy. Administration of measles virus and VSV vectors have demonstrated immune responses, tumor regression, and tumor eradication in various animal models. A limited number of clinical trials have shown well-tolerated treatment, good safety profiles, and dose-dependent activity in cancer patients.
Topics: Male; Animals; Humans; RNA Viruses; Viruses; Neoplasms; RNA; Immunization; Genetic Vectors; Zika Virus; Zika Virus Infection
PubMed: 35169298
DOI: 10.1038/s41417-022-00436-7 -
Nature Communications Sep 2023Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate....
Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA vaccines that encode for the wild-type Lassa virus strain Josiah glycoprotein complex or the prefusion stabilized conformation of the Lassa virus glycoprotein complex. Hartley guinea pigs were vaccinated with two 10 µg doses, 28 days apart, of either construct. Vaccination induced strong binding antibody responses, specific to the prefusion conformation of glycoprotein complex, which were significantly higher in the prefusion stabilized glycoprotein complex construct group and displayed strong Fc-mediated effects. However, Lassa virus-neutralizing antibody activity was detected in some but not all animals. Following the challenge with a lethal dose of the Lassa virus, all vaccinated animals were protected from death and severe disease. Although the definitive mechanism of protection is still unknown, and assessment of the cell-mediated immune response was not investigated in this study, these data demonstrate the promise of mRNA as a vaccine platform against the Lassa virus and that protection against Lassa virus can be achieved in the absence of virus-neutralizing antibodies.
Topics: Humans; Guinea Pigs; Animals; Lassa virus; Antibodies, Neutralizing; Arenaviridae; mRNA Vaccines; Glycoproteins
PubMed: 37699929
DOI: 10.1038/s41467-023-41376-6 -
Virulence Dec 2023Recent viral hemorrhagic fever (VHF) disease outbreaks caused by Ebola virus (EBOV) and Marburg virus (MARV) in West Africa are unique and alarming. The intents of this...
Recent viral hemorrhagic fever (VHF) disease outbreaks caused by Ebola virus (EBOV) and Marburg virus (MARV) in West Africa are unique and alarming. The intents of this editorial are to highlight what is known about these viruses and the disease outbreaks that they cause in the African continent and elsewhere and to raise awareness of a related virus called Lassa virus (LASV) that causes endemic viral hemorrhagic fever infections and frequent outbreaks in West Africa.
Topics: Humans; Hemorrhagic Fevers, Viral; Lassa virus; Ebolavirus; Africa, Western; Disease Outbreaks; Hemorrhagic Fever, Ebola
PubMed: 36748841
DOI: 10.1080/21505594.2023.2176980 -
Virulence Dec 2023Mammarenaviruses, a genus of the family , are capable of infecting mammals and are primarily found in rodent reservoirs worldwide. Mammarenaviruses can be transmitted to...
Mammarenaviruses, a genus of the family , are capable of infecting mammals and are primarily found in rodent reservoirs worldwide. Mammarenaviruses can be transmitted to humans through contact with infected rodents, and though infection is often asymptomatic, some members of this genus can cause viral haemorrhagic fever which has mortality rates ranging from 1% to 50%. These viruses are typically restricted geographically, based on the geographical range of their host reservoirs. Lymphocytic choriomeningitis virus (LCMV) was previously thought to be the only mammarenavirus found across the globe. However, recent discoveries of two novel human mammarenaviruses, Wenzhou Virus (WENV) and Plateau Pika Virus (PPV), in Asia and Southeast Asia show that mammarenaviruses are more widespread than previously thought. This editorial article aims to raise awareness about these emerging viruses, their genetic and ecological diversities, and clinical significance, and to encourage further study of these emerging viruses.
Topics: Animals; Humans; Arenaviridae; Lymphocytic choriomeningitis virus; Asia, Southeastern; Asia; Mammals
PubMed: 37394841
DOI: 10.1080/21505594.2023.2231392