ETIDIOH - NEW

  Abstract Background :  Lassa fever (LF) is an acute viral hemorrhagic illness endemic to West Africa, with no licensed vaccines or targeted treatments available, highlighting a critical gap in global health preparedness. T cell-mediated immunity plays a central role in viral control and survival. Synthetic DNA vaccines offer a promising strategy to induce both humoral and cellular immunity against LF. Methods :  A Phase 1b, randomized, double-blind, placebo-controlled trial was conducted to assess the safety, tolerability, and immunogenicity of INO-4500 , a DNA vaccine encoding the Lassa virus (Josiah strain) glycoprotein precursor (GPC). A total of 220 healthy adults were randomized to receive either 1 mg or 2 mg of INO-4500 (intervention), or placebo, administered intradermally (ID) followed by electroporation (EP) at Day 0 and Week 4. Safety was evaluated through Week 48. Primary immunogenicity endpoints included humoral and cellular immune responses at multiple time...

  Abstract Background No vaccine is currently available for Lassa fever, a viral hemorrhagic disease that is estimated to cause thousands of deaths each year in western Africa . A replication-competent recombinant vesicular stomatitis virus–vectored vaccine encoding a Lassa virus (LASV) glycoprotein complex, rVSVΔG-LASV-GPC, has been developed, but data on its safety and immunogenicity are limited. Methods In this phase 1, double-blind trial conducted in the United States and Liberia, we randomly assigned healthy adults (18 to 50 years of age) to receive rVSVΔG-LASV-GPC or placebo intramuscularly . Participants received a single vaccine dose of 2×104 plaque-forming units (PFU), 2×105 PFU, 2×106 PFU, or 2×107 PFU or placebo or received two vaccine doses of 2×107 PFU or placebo, within a window of 6 to 20 weeks. The side-effect profile was assessed according to the incidence of solicited and unsolicited adverse events (primary end point). Because Lassa fever can cause sensorineural h...

Abstract Lassa mammarenavirus (LASV), a member of the family Arenaviridae , is a highly pathogenic virus capable of causing severe systemic infections in humans . The primary host reservoir is the Natal multimammate mouse (Mastomys natalensis), with human infections typically occurring through mucosal exposure to virus-containing aerosols from rodent excretions . To better understand the molecular mechanisms underlying LASV replication in the respiratory tract, we utilized differentiated primary human airway epithelial cells (HAECs) grown under air–liquid interface conditions, closely mimicking the bronchial epithelium in vivo. Our findings demonstrate that HAECs are permissive to LASV infection and support productive virus replication . While LASV entry into polarized HAECs occurred through both apical and basolateral surfaces , progeny virus particles were predominantly released from the apical surface , consistent with an intrinsic apical localization of the envelope glycoprotein GP...

{Excerpt} Highlights •  A new strain of Lassa virus (LASV) was successfully isolated and characterized. •  The combination of ribavirin and LHF-535 has been demonstrated to exhibit synergistic effects in inhibiting LASV. •  The findings provide new directions for the development of antiviral drugs and vaccines for Lassa fever. Dear Editor, Lassa virus (LASV) is the causative agent of the acute viral hemorrhagic Lassa fever (LF), which is classified into Mammarenavirus within the Arenaviridae family , with a single-stranded, negative-sense, bi-segmented RNA genome. Due to its high pathogenicity and lethality , LASV is considered as a priority threat to public health , with an estimated cases of 300,000 infections and 5,000 deaths annually . LASV was first isolated and described as a clinical entity in 1969 in Lassa, Nigeria (Garry, 2023). LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up t...

The UK Health Security Agency has been informed under the International Health Regulations that an individual travelled to England from Nigeria while they were unwell with Lassa fever at the end of February. The individual returned to Nigeria where they were diagnosed . We are now working to identify people who were in contact with the affected individual while they were in the country. Lassa fever does not spread easily between people and the overall risk to the public is very low . If you have not been contacted by UKHSA then you are very unlikely to have had any exposure to Lassa fever and do not need to take action. Lassa fever causes acute infections which can range from very mild symptoms through to a severe viral haemorrhagic fever. People usually become infected with Lassa virus through exposure to food or household items contaminated with urine or faeces of infected rats – present in some West African countries where the disease is endemic. The virus can also be spread between...