Demonstration of the Pre-Emergency Use Authorization Path Using 3 Minor Groove Binder-Hydrolysis Probe Assays to Detect Escherichia coli O104:H4.

Background: The Department of Defense (DoD) and the Food and Drug Administration (FDA) have collaboratively worked on a pre-Emergency Use Authorization (pre-EUA) process for in vitro diagnostic (IVD) devices, using FDA's regulatory flexibilities under the EUA authorities. The pre-EUA process enables FDA review of data in anticipation of a request for an EUA, advancing US government public health emergency preparedness efforts.

Methods: The IVD device developed to detect Escherichia coli O104:H4, for which an EUA has not been issued, serves as an example to illustrate that process.

Evaluation of ViroCyt® Virus Counter for rapid filovirus quantitation.

Development and evaluation of medical countermeasures for diagnostics, vaccines, and therapeutics requires production of standardized, reproducible, and well characterized virus preparations. For filoviruses this includes plaque assay for quantitation of infectious virus, transmission electron microscopy (TEM) for morphology and quantitation of virus particles, and real-time reverse transcription PCR for quantitation of viral RNA (qRT-PCR). The ViroCyt® Virus Counter (VC) 2100 (ViroCyt, Boulder, CO, USA) is a flow-based instrument capable of quantifying virus particles in solution.

Therapeutic intervention of Ebola virus infection in rhesus macaques with the MB-003 monoclonal antibody cocktail.

Ebola virus (EBOV) remains one of the most lethal transmissible infections and is responsible for high fatality rates and substantial morbidity during sporadic outbreaks. With increasing human incursions into endemic regions and the reported possibility of airborne transmission, EBOV is a high-priority public health threat for which no preventive or therapeutic options are currently available. Recent studies have demonstrated that cocktails of monoclonal antibodies are effective at preventing morbidity and mortality in nonhuman primates (NHPs) when administered as a post-exposure prophylactic within 1 or 2 days of challenge.

Drs2p-dependent formation of exocytic clathrin-coated vesicles in vivo.

The small GTP binding protein ARF has been implicated in budding clathrin-coated vesicles (CCVs) from Golgi and endosomal membranes. An arf1 synthetic lethal screen identified DRS2/SWA3 along with a clathrin heavy-chain conditional allele (chc1-5/swa5-1) and SWA2, encoding the yeast auxilin-like protein involved in uncoating CCVs. Drs2p/Swa3p is a P-type ATPase and a potential aminophospholipid translocase that localizes to the trans-Golgi network (TGN) in yeast.