Abstract
The continuing outbreaks of ebola virus disease highlight the ongoing threat posed by filoviruses. Fortunately, licensed vaccines and therapeutics are now available for Zaire ebolavirus. However, effective medical countermeasures, such as vaccines for other filoviruses such as Sudan ebolavirus and the Marburg virus, are presently in early stages of development and, in the absence of a large outbreak, would require regulatory approval via the U.S. Food and Drug Administration (FDA) Animal Rule. The selection of an appropriate animal model and virus challenge isolates for nonclinical studies are critical aspects of the development program. Here, we have focused on the recommendation of challenge isolates for Sudan ebolavirus and Marburg virus. Based on analyses led by the Filovirus Animal and Nonclinical Group (FANG) and considerations for strain selection under the FDA Guidance for the Animal Rule, we propose prototype virus isolates for use in nonclinical challenge studies.
Highlights
The Filoviridae family represents a group of filamentous, single-stranded, negativesense RNA viruses known as the filoviruses [1,2]
The largest outbreak of ebolavirus disease (EVD) occurred in 2014–2016, resulting in more than 28,000 cases and 11,000 deaths as a result of infections by the EBOV, which triggered global investments to advance the development of medical countermeasures
In order to be consistent with the requirements of the Food and Drug Administration (FDA) Animal Rule, the challenge agent should be a low-passage isolate from a human fatal case that produces an infection in the animal model, that can be used to evaluate medical countermeasures intended to treat the authentic human disease
Summary
The Filoviridae family represents a group of filamentous, single-stranded, negativesense RNA viruses known as the filoviruses [1,2]. The largest outbreak of ebolavirus disease (EVD) occurred in 2014–2016, resulting in more than 28,000 cases and 11,000 deaths as a result of infections by the EBOV, which triggered global investments to advance the development of medical countermeasures. The SUDV has caused seven outbreaks of SUDV disease (SDV) to date, with the most consequential occurring in South Sudan in 2000, infecting over 400 people with a case fatality ratio of 53 percent [5]. Through 2020, twelve different outbreaks of MVD have occurred, with a total of 466 documented cases [8], with the most consequential occurring in 2004–2005 in Angola, resulting in 252 infections and a case fatality ratio of 90 percent. The only medical intervention for MVD available is palliative care
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