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Ebola virus From Outbreak to Defense Mariia Sergeeva, PhD Ebola virus infection Bio risk group 4 - highest (BSL4) Bolivian and Argentine hemorrhagic fevers Marburg virus Ebola virus Hantaviruses Lassa fever virus Crimean–Congo hemorrhagic fever • Severe to fatal disease • High individual and community risk • No specific treatments currently available The Ebola virus Natural reservoir of virus Virus transmission Virus transmission Through broken skin or mucous membranes in, for example, the eyes, nose, or mouth • Environmental exposure - entering caves, buildings infested with bats • Direct contact of infected animals (primates, bats) – consumption Human to human transmission High Risk Exposures • Direct care of an EVD patient or exposure to body fluids without standard biosafety precautions • Laboratory worker processing body fluids of confirmed EVD patients without appropriate PPE or standard biosafety precautions • Participation in funeral rites which include direct exposure to human remains in the geographic area where outbreak is occurring without appropriate PPE Low Risk Exposures • Household member or other casual contact with an EVD patient Course of Disease • Incubation period: 8-10 days (rarely from 2–21 days) • Onset of symptoms • Virus quantity increases 3-5 days post-onset • If patient survives to day 14, increased chance of survival • Convalescence/resolution of viremia Ebola symptoms Hemorrhagic fever • Direct endothelium cells destruction, “cytokine storm”, generalized immunosuppression • Hemorrhagic symptoms in ~ 45% of cases • Mild: bruising, nose bleed, etc. • Severe: bloodily stools, multi-organ shock • Death of multi-organ failure, acute respiratory distress syndrome, coagulopathy Ebola virus outbreaks since 1976 Ebola situation report 29/08/2014 Ebola situation report 22/10/2014 Ebola situation report 21/11/2014 2014 Ebola outbreak 2014 Ebola outbreak 2014 Ebola outbreak Heavy casualties among health-care workers Infected - 588 94 in Guinea; 341 in Liberia; 2 in Mali; 11 in Nigeria; 136 in Sierra Leone; 1 in Spain; 3 in the USA Died - 337 Urgent need for specific prophylaxis development 2014 Ebola outbreak • The WHO Emergency Committee regarding the 2014 Ebola Virus Disease outbreak highlighted that a coordinated international response is deemed essential to stop spread of Ebola epidemic. • Active vaccine development and trials are ongoing in the several countries Ebola treatment trials Product Type Developer Partner ZMapp Drug TKM- Ebola Drug Tekmira Pharmaceuticals MCS-BDTX, JPM-MCS Phase I Brincidofovir Drug Chimerix CDC, NIH Phase 2 NIAID/GSK Ebola Vaccine GlaxoSmithKline NIAID Phase I BCX4430 Drug BioCryst Pharmaceuticals NIAID, USAMRIID Preclinical Favipiravir Drug Toyama Chemical Co. Ltd. MediVector, USAMRIID Preclinical AVI-7537 Drug Sarepta Therapeutics MCS-BDTX, JPM-MCS Phase 1 VSV-EBOV Vaccine NewLink Genetics PHAC, DTRA, WRAIR Phase 1 Alferon and Ampligen Drug Hemispherx Biopharma USAMRIID Preclinical TBD Drug NanoViricides N/A Preclinical Hyperimmune horse sera Drug Fab'entech Bpifrance Feasibility SynCon Vaccine Inovio Pharmaceuticals GeneOne Life Science Pre-IND VesiculoVax Vaccine Profectus Biosciences BARDA, HHS, DoD, NIAID, Army Preclinical Ebola Vaccine Vaccine Crucell NIAID Phase I MVA-BN Filo Vaccine Bavarian Nordic NIAID Preclinical JK- 05 Drug Sihuan Pharmaceutical AMMS Preclinical DPX-Ebola Vaccine Immunovaccine Inc. NIH/NIAID Preclinical TBD Vaccine Protein Sciences Corporation NIH Preclinical LeafBio , Mapp Biopharmaceutical Defyrus, USAMRIID, NIAID, PHAC Phase Preclinical Ebola vaccines • rVSV-ZEBOV (NewLink Genetics) is based on the recombinant vesicular stomatitis virus carrying Ebola virus GP - entered clinical trials • ChimpAd3-ZEBOV (GlaxoSmithKline) is based on the modified chimpanzee adenovirus carrying Ebola virus GP and NP - entered clinical trials • Human parainfluenza virus type 3 -based candidate vaccine developed by University of Texas (USA) (Bukreyev et al., 2010) - going to enter clinical trials in the nearest future. • Completed clinical trials are adenoviral vector-based vaccine (ClinicalTrials ID: NCT00374309) and Ebola DNA plasmid vaccine (ClinicalTrials ID: NCT00605514) - the results have not yet been published. Ministry of Healthcare of the Russian Federation Research Institute of Influenza Gamaleya Research Institute for Epidemiology and Microbiology Anti-Ebola vaccine and therapeutics Research Institute of Influenza Gamaleya Research Institute for Epidemiology and Microbiology • Influenza-based recombinant vector vaccine • Adenovirus-based vaccine • Chemotherapy drugs belonging to the group of azolo-azines • Therapeutic mini-antibodies Ebola virus and Influenza virus The Ebola virus The Ebola virus: high rate of mutations In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response. Research Institute of Influenza programmes Chemotherapy drugs Triazavirin and azolo-azines Influenza-based recombinant vector vaccine Thank you for attention Contact info: [email protected] +78124991534 +79215898308 Ebola diagnostics IgM IgG viremia 0 3 days post onset of symptoms 10 Fever RT-PCR ELISA IgM ELISA IgG