Publications by authors named "F E M Scholte"
Reverse genetic systems are powerful tools in molecular virology that allow the generation of infectious recombinant virus and the manipulation of viral genomes. Reverse genetic systems enable the incorporation of reporter genes, facilitating many virological assays, including high-throughput screening. Additionally, reverse genetic systems can be used to introduce targeted mutations into the viral genome, allowing investigations of viral genetic elements and protein functions in virus pathogenesis and biology.
View Article and Find Full Text PDFAdvancement of vaccine candidates that demonstrate protective efficacy in screening studies necessitates detailed safety and immunogenicity investigations in pre-clinical models. A non-spreading Crimean-Congo hemorrhagic fever virus (CCHFV) viral replicon particle (VRP) vaccine was developed for single-dose administration to protect against disease. To date, several studies have supported safety, immunogenicity, and efficacy of the CCHF VRP in multiple highly sensitive murine models of lethal disease, but the VRP had yet to be evaluated in large animals.
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- Development of broad-spectrum antiviral therapies, like 4'-fluorouridine (4'-FlU), is crucial for effectively responding to outbreaks and pandemics caused by emerging viruses, particularly those that cause hemorrhagic fevers, which have seen increasing morbidity and mortality rates.
- 4'-FlU has shown antiviral activity against several hemorrhagic fever viruses in cell cultures and has demonstrated high efficacy in guinea pig models infected with lethal arenaviruses, maintaining its effectiveness at low doses.
- When administered late in infection, 4'-FlU not only resolved clinical symptoms quickly but also showcased its potential as a therapeutic option with a broader application against various viral pathogens.
Immunizing mice with Crimean-Congo hemorrhagic fever virus (CCHFV) nucleoprotein (NP), glycoprotein precursor (GPC), or with the GP38 domain of GPC, can be protective when the proteins are delivered with viral vectors or as a DNA or RNA vaccine. Subunit vaccines are a safe and cost-effective alternative to some vaccine platforms, but Gc and Gn glycoprotein subunit vaccines for CCHFV fail to protect despite eliciting high levels of neutralizing antibodies. Here, we investigated humoral and cellular immune responses and the protective efficacy of recombinant NP, GP38, and GP38 forms (GP85 and GP160) associated with the highly glycosylated mucin-like (MLD) domain, as well as the NP + GP38 combination.
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