Whole-genome sequencing surveillance of Siberian tick-borne encephalitis virus (TBEV) identifies an additional lineage in Kyrgyzstan.

Tick-borne encephalitis virus (TBEV) is the most prevalent tick-borne viral disease in Europe and Asia. There are three main subtypes of the virus: European, Siberian, and Far Eastern, each of which having distinctive ecology, clinical presentation, and geographic distribution. In recent years, other TBEV subtypes have been described, namely the Himalayan and Baikalian subtypes.

Recombinant Vaccine Production: Production of a Recombinant CCHF MVA Vaccine.

One of the key interventions against infection is immunization, including an increasing focus on development of vaccines against pathogenic bunyaviruses. Whilst different vaccine development approaches exist, recombinant viral vaccines have a strong safety record, are rapid to produce, are cost-effective, and have been demonstrated to be rolled out in response to outbreaks, including in low- and middle-income countries. One viral vector, modified Vaccinia Ankara (MVA), has been used to develop vaccine candidates against Crimean-Congo Haemorrhagic Fever (CCHF) virus through incorporation of the nucleoprotein (NP) and glycoprotein (GP) regions, with the former candidate having now progressed to being the first vaccine against CCHF virus to enter Phase 1 clinical trials.

Lymphocytic choriomeningitis arenavirus utilises intercellular connections for cell to cell spread.

The Arenaviridae family of segmented RNA viruses contains nearly 70 species with several associated with fatal haemorrhagic fevers, including Lassa, Lujo and Junin viruses. Lymphocytic choriomeningitis arenavirus (LCMV) is associated with fatal neurologic disease in humans and additionally represents a tractable model for studying arenavirus biology. Within cultured cells, a high proportion of LCMV spread is between directly neighbouring cells, suggesting infectivity may pass through intercellular connections, bypassing the canonical extracellular route involving egress from the plasma membrane.

Crimean-Congo haemorrhagic fever among healthcare workers in Iran 2000-2023, a report of National Reference Laboratory.

Background: Crimean-Congo haemorrhagic fever (CCHF) is a lethal acute viral zoonosis with a case fatality rate of 5-50%. Due to the potential of human-to human transmission of the disease, healthcare workers (HCWs) are at risk of occupational exposure to CCHF virus. Little is known about CCHF virus route of transmission and risks in Iranian HCWs.

Research and product development for Crimean-Congo haemorrhagic fever: priorities for 2024-30.

Crimean-Congo haemorrhagic fever (CCHF) is a widely distributed and potentially fatal tick-borne viral disease with no licensed specific treatments or vaccines. In 2019, WHO published an advanced draft of a research and development roadmap for CCHF that prioritised the development and deployment of the medical countermeasures most needed by CCHF-affected countries. This Personal View presents updated CCHF research and development priorities and is the product of broad consultation with a working group of 20 leading experts in 2023-24.

Understanding Viral Haemorrhagic Fevers: Virus Diversity, Vector Ecology, and Public Health Strategies.

Viral haemorrhagic fevers encompass a diverse group of severe, often life-threatening illnesses caused by viruses from multiple families, including , , , , and . Characterised by fever and haemorrhagic symptoms, these diseases challenge public health systems by overwhelming healthcare facilities, complicating diagnostic processes, and requiring extensive resources for containment and treatment, especially in resource-limited settings. This discussion explores the intricate relationships between VHFs and their transmission vectors-both animal and arthropod-and examines the impact of ecological and geographic factors on disease spread.

Development of targeted whole genome sequencing approaches for Crimean-Congo haemorrhagic fever virus (CCHFV).

Crimean-Congo haemorrhagic fever (CCHF) is the most prevalent human tick-borne viral disease, with a reported case fatality rate of 30 % or higher. The virus contains a tri-segmented, negative-sense RNA genome consisting of the small (S), medium (M) and large (L) segments encoding respectively the nucleoprotein (NP), the glycoproteins precursor (GPC) and the viral RNA-dependent RNA polymerase (RDRP). CCHFV is one of the most genetically diverse arboviruses, with seven distinct lineages named after the region they were first reported in and based on S segment phylogenetic analysis.

Convalescent human plasma candidate reference materials protect against Crimean-Congo haemorrhagic fever virus (CCHFV) challenge in an A129 mouse model.

Crimean-Congo Haemorrhagic Fever Virus (CCHFV) is spread by infected ticks or direct contact with blood, tissues and fluids from infected patients or livestock. Infection with CCHFV causes severe haemorrhagic fever in humans which is fatal in up to 83 % of cases. CCHFV is listed as a priority pathogen by the World Health Organization (WHO) and there are currently no widely-approved vaccines.

Third International Conference on Crimean-Congo Hemorrhagic Fever in Thessaloniki, Greece, September 19-21, 2023.

The Third International Conference on Crimean-Congo Hemorrhagic Fever (CCHF) was held in Thessaloniki, Greece, September 19-21, 2023, bringing together a diverse group of international partners, including public health professionals, clinicians, ecologists, epidemiologists, immunologists, and virologists. The conference was attended by 118 participants representing 24 countries and the World Health Organization (WHO). Meeting sessions covered the epidemiology of CCHF in humans; Crimean-Congo hemorrhagic fever virus (CCHFV) in ticks; wild and domestic animal hosts; molecular virology; pathogenesis and animal models; immune response related to therapeutics; and CCHF prevention in humans.

Lymphocytic choriomeningitis arenavirus requires cellular COPI and AP-4 complexes for efficient virion production.

Unlabelled: Lymphocytic choriomeningitis virus (LCMV) is a bisegmented negative-sense RNA virus classified within the family of the order. LCMV is associated with fatal disease in immunocompromized populations, and as the prototypical arenavirus, acts as a model for the many serious human pathogens within this group. Here, we examined the dependence of LCMV multiplication on cellular trafficking components using a recombinant LCMV expressing enhanced green fluorescent protein in conjunction with a curated siRNA library.

Transauricular nerve stimulation in acute ischaemic stroke requiring mechanical thrombectomy: Protocol for a phase 2A, proof-of-concept, sham-controlled randomised trial.

Background: Labile blood pressure after acute ischaemic stroke requiring mechanical thrombectomy is independently associated with poor patient outcomes.

Objectives: This study protocol describes is designed to determine whether transauricular nerve stimulation, improves baroreflex sensitivity, reduces blood pressure variability in the first 24 hours after acute ischaemic stroke requiring mechanical thrombectomy.

Design: Phase 2a, Proof-of-concept, Sham-controlled Randomised Trial: Methods and Analysis: 36 individuals undergoing mechanical thrombectomy for acute ischaemic stroke with established hypertension aged >18 years will be randomly allocated to receive bilateral active or sham transauricular nerve stimulation for the duration of the mechanical thrombectomy procedure (AffeX-CT/001 investigational device).

Recovery of complete genome sequences of Crimean-Congo haemorrhagic fever virus (CCHFV) directly from clinical samples: A comparative study between targeted enrichment and metagenomic approaches.

Crimean-Congo haemorrhagic fever (CCHF) is the most prevalent human tick-borne viral disease, endemic to the Balkans, Africa, Middle East and Asia. There are currently no licensed vaccines or effective antivirals against CCHF. CCHF virus (CCHFV) has a negative sense segmented tripartite RNA genome consisting of the small (S), medium (M) and large (L) segments.

Systems-level temporal immune-metabolic profile in Crimean-Congo hemorrhagic fever virus infection.

Crimean-Congo hemorrhagic fever (CCHF) caused by CCHF virus (CCHFV) is one of the epidemic-prone diseases prioritized by the World Health Organisation as public health emergency with an urgent need for accelerated research. The trajectory of host response against CCHFV is multifarious and remains unknown. Here, we reported the temporal spectrum of pathogenesis following the CCHFV infection using genome-wide blood transcriptomics analysis followed by advanced systems biology analysis, temporal immune-pathogenic alterations, and context-specific progressive and postinfection genome-scale metabolic models (GSMM) on samples collected during the acute (T0), early convalescent (T1), and convalescent-phase (T2).

Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab') fragments.

The development of new therapies against SARS-CoV-2 is required to extend the toolkit of intervention strategies to combat the global pandemic. In this study, hyperimmune plasma from sheep immunised with whole spike SARS-CoV-2 recombinant protein has been used to generate candidate products. In addition to purified IgG, we have refined candidate therapies by removing non-specific IgG via affinity binding along with fragmentation to eliminate the Fc region to create F(ab') fragments.

Use of a Preclinical Natural Transmission Model to Study Antiviral Effects of a Carbohydrate-Binding Module Therapy against SARS-CoV-2 in Hamsters.

The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and its expansion to a worldwide pandemic resulted in efforts to assess and develop interventions to reduce the disease burden. Despite the introduction of vaccine programmes against SARS-CoV-2, global incidence levels in early 2022 remained high, demonstrating a need for the development of physiologically relevant models, which are essential for the identification of alternative antiviral strategies. The hamster model of SARS-CoV-2 infection has been widely adopted due to similarities with humans in terms of host cell entry mechanism (via ACE2), and aspects of symptomology and virus shedding.

Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge model.

Background: The tick-borne bunyavirus, Crimean-Congo Haemorrhagic Fever virus (CCHFV), can cause severe febrile illness in humans and has a wide geographic range that continues to expand due to tick migration. Currently, there are no licensed vaccines against CCHFV for widespread usage.

Methods: In this study, we describe the preclinical assessment of a chimpanzee adenoviral vectored vaccine (ChAdOx2 CCHF) which encodes the glycoprotein precursor (GPC) from CCHFV.

Climate change and infectious disease: A prologue on multidisciplinary cooperation and predictive analytics.

Climate change impacts global ecosystems at the interface of infectious disease agents and hosts and vectors for animals, humans, and plants. The climate is changing, and the impacts are complex, with multifaceted effects. In addition to connecting climate change and infectious diseases, we aim to draw attention to the challenges of working across multiple disciplines.

Investigating the effect of ribavirin treatment on genetic mutations in Crimean-Congo haemorrhagic fever virus (CCHFV) through next-generation sequencing.

Crimean-Congo haemorrhagic fever (CCHF) is the most widespread tick-borne viral haemorrhagic fever affecting humans, and yet a licensed drug against the virus (CCHFV) is still not available. While several studies have suggested the efficacy of ribavirin against CCHFV, current literature remains inconclusive. In this study, we have utilised next-generation sequencing to investigate the mutagenic effect of ribavirin on the CCHFV genome during clinical disease.

Development of humanised antibodies for Crimean-Congo Haemorrhagic fever virus: Comparison of hybridoma-based versus phage library techniques.

Humanised antibodies targeting Crimean-Congo Haemorrhagic virus (CCHFV) are needed for the development and standardisation of serological assays. These assays are needed to address a shortfall in available tests that meet regulatory diagnostic standards and to aid surveillance activities to extend knowledge on the distribution of CCHFV. To generate a humanised monoclonal antibody against CCHFV, we have compared two methods: the traditional mouse hybridoma approach with subsequent sequencing and humanisation of antibodies versus a non-animal alternative using a human combinatorial antibody library (HuCAL).

Development of anti-Crimean-Congo hemorrhagic fever virus Gc and NP-specific ELISA for detection of antibodies in domestic animal sera.

Crimean-Congo hemorrhagic fever (CCHF) is a priority emerging disease. CCHF, caused by the CCHF virus (CCHFV), can lead to hemorrhagic fever in humans with severe cases often having fatal outcomes. CCHFV is maintained within a tick-vertebrate-tick cycle, which includes domestic animals.

Activity of a Carbohydrate-Binding Module Therapy, Neumifil, against SARS-CoV-2 Disease in a Hamster Model of Infection.

The rapid global spread of severe acute respiratory coronavirus 2 (SARS-CoV-2) has resulted in an urgent effort to find efficacious therapeutics. Broad-spectrum therapies which could be used for other respiratory pathogens confer advantages, as do those based on targeting host cells that are not prone to the development of resistance by the pathogen. We tested an intranasally delivered carbohydrate-binding module (CBM) therapy, termed Neumifil, which is based on a CBM that has previously been shown to offer protection against the influenza virus through the binding of sialic acid receptors.

Development of a cost-effective ovine antibody-based therapy against SARS-CoV-2 infection and contribution of antibodies specific to the spike subunit proteins.

Antibodies against SARS-CoV-2 are important to generate protective immunity, with convalescent plasma one of the first therapies approved. An alternative source of polyclonal antibodies suitable for upscaling would be more amendable to regulatory approval and widespread use. In this study, sheep were immunised with SARS-CoV-2 whole spike protein or one of the subunit proteins: S1 and S2.