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: maria_s@influenza.spb.ru+78124991534+79215898308

Ebola diagnostics

viremia

3

IgM

ELISA IgM

0 10

IgG

ELISA IgG

days post onset of symptoms

RT-PCR

Fever