Characterization of Ebola Virus from an Ongoing Outbreak in Ituri and North Kivu, DR Congo to Guide to Response Activities

Background: The ongoing Ebola virus (EBOV) outbreak in the Ituri and North Kivu provinces of the Democratic Republic of Congo (DRC) is the second largest ever recorded. Despite civil unrest, outbreak control measures, and the administration of experimental therapies and a vaccine, have been initiated. Lacking a virus isolate from this outbreak, we rescued recombinant, infectious EBOV-Ituri virus from plasmid DNA. Methods: We report a phylogenetic analysis of EBOV-Ituri. In addition, we evaluated experimental therapeutics currently undergoing clinical trials in DRC: remdesivir (GS-5734) and ZMapp monoclonal antibodies (mAbs) to inhibit EBOVI-Ituri. We also tested diagnostic assays used in DRC for detection of the EBOV-Ituri sequence despite having mismatches in the primer binding sites. EBOV-Ituri results were compared with the 2013-2016 outbreak EBOV-Makona. Findings: Our analysis suggests there are at least 2 EBOV strains in DRC, which have independently crossed into the human population. The EBOV-Ituri strain initially grew significantly slower than EBOV-Makona from the 2013-2016 outbreak, yet reached similar titers by 72H p.i. EBOV-Ituri was similar to EBOV-Makona in its susceptibility to inhibition by remdesivir, neutralizing ZMapp, and other EBOV mAbs. The Xpert Ebola and CDC RT-qPCR diagnostic assays detected EBOV-Ituri with high sensitivity despite primer site binding mismatches. Interpretation: Our findings provide a rationale for the continued testing of investigational therapies, confirm the effectiveness of the diagnostic assay used in the region, and establish a paradigm for the use of reverse genetics-launched strains to inform response activities in an ongoing outbreak. Funding: US Centers for Disease Control and Prevention. Declaration of Interest: Danielle Porter is an employee of Gilead. Ethical Approval: Not needed.