Abstract
.Filoviruses, which include ebolaviruses and marburgvirus, can cause outbreaks of highly lethal hemorrhagic fever. This disease causes significant morbidity and mortality in humans and non-human primates, with human fatality rates reaching 90% during some outbreaks. Currently, there is lack of licensed vaccines or antivirals for these viruses. Since early symptoms of filovirus infection mimic more common diseases, there is a strong unmet public health and biodefense need for broad-spectrum filovirus rapid diagnostics. We have generated a panel of mouse single-chain Fv-antibodies (scFvs) to filovirus glycoproteins (GPs) using cell-free ribosome display and determined their cross-reactivity profiles to all known filovirus species. Two scFvs (4-2 and 22-1) were able to detect all known Ebolavirus and Marburgvirus species. This is the first report on ribosome display scFvs that can detect a broad set of filovirus GPs, which demonstrates the potential for use in diagnostics.
Highlights
The recent Ebola virus pandemic was a health crisis with global repercussions (PMID: 27813879)
We report the use of a rapid, cell-free ribosomal display system to isolate a panel of single-chain Fvantibodies (scFvs) that can bind the glycoprotein (GP) of EBOV, SUDV, Reston virus (RESTV), BDBV, TAFV, and MARV
To determine whether ribosomal display is suitable for generation of antibodies against filoviruses, we vaccinated mice with viruslike particles (VLPs) consisting of EBOV VP40 and GP
Summary
The recent Ebola virus pandemic was a health crisis with global repercussions (PMID: 27813879). There are six filoviruses known to be pathogenic in humans: four ebolaviruses (Ebola [EBOV], Sudan [SUDV], Tai Forest [TAFV], and Bundibugyo [BDBV]) and two marburgviruses (Ravn [RAVV] and Marburg [MARV]) (PMID: 21046175). Diagnostics for active infection are largely based on realtime PCR assays. These are rapid, highly sensitive and specific detection, these methods are expensive and require an instrument with hands-on preparation for proper use. There are ELISA-based detection platforms for EBOV, SUDV, and BDBV VP40, but sensitivity and specificity are low relative to PCR-based assays.[1] most of the diagnostic platforms of all types have centered on detection of EBOV. In the presence of selective pressure, filoviruses have been shown to readily mutate.[6,7,8,9,10] There is, a strong unmet public health and biodefense need for broad-spectrum rapid diagnostics and outbreak control
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