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

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Summary

Introduction

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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