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:
maria_s@influenza.spb.ru
+78124991534
+79215898308
Ebola diagnostics
IgM
IgG
viremia
0
3
days post onset of
symptoms
10
Fever
RT-PCR
ELISA IgM
ELISA IgG