Ebola virus From Outbreak to Defense Mariia Sergeeva, PhD.
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Transcript of Ebola virus From Outbreak to Defense Mariia Sergeeva, PhD.
Ebola virus From Outbreak to Defense
Mariia Sergeeva, PhD
Ebola virus infection
Bio risk group 4 - highest (BSL4)
Bolivian and Argentine hemorrhagic feversMarburg virusEbola virusHantavirusesLassa fever virusCrimean–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 transmissionThrough 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 transmissionHigh 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
• 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
Hemorrhagic fever
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
• 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
2014 Ebola outbreak
Ebola treatment trialsProduct Type Developer Partner Phase
ZMapp Drug LeafBio , Mapp Biopharmaceutical Defyrus, USAMRIID, NIAID, PHAC
Preclinical
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
• 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.
Ebola vaccines
Ministry of Healthcare of the Russian Federation
Research Institute of InfluenzaGamaleya Research Institute for Epidemiology and Microbiology
Anti-Ebola vaccine and therapeutics
Research Institute of Influenza
•Influenza-based recombinant vector vaccine
•Chemotherapy drugs belonging to the group of azolo-azines
Gamaleya Research Institute for Epidemiology and Microbiology
•Adenovirus-based vaccine
•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
viremia
3
IgM
ELISA IgM
0 10
IgG
ELISA IgG
days post onset of symptoms
RT-PCR
Fever