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VIRUS ALERT!
EBOLA: Will we be safe?
One Year Ago
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1 victim
Vector
Symptoms
Mode of Infection
Previous Breakouts
•13,676
•7606
•4910
Development
• cAd3-ZEBOV
– Chimp Adenovirus type 3
• VSV-EBOV
– Vesicular Stomatitis Virus
• ZMapp
Underlying Mechanisms
Underlying Mechanism: rVSV- EBOV
• rVSV – recombinant vesicular stomatitis virusbased vaccine
• Live-attenuated
• Animal virus, asymptomatic in humans
• Favorable features:
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Replication in all mammalian cell lines
High titres
Strong induction of innate and adaptive immunity
Low levels of pre-existing immunity to VSV in
general population
rVSV vaccine
1. Removal of VSV glycoprotein
(G) gene (rVSVΔG)
2. Insertion of Ebola virus (EBOV)
glycoproteins (rVSV/EBOV-GP)
3. Tranfection of VSV genomic
plasmid and expression
plasmids in cell culture
4. Production of recombinant
VSV proteins
N – nucleoprotein
P - phosphoprotein
L – polymerase
Underlying Mechanism: cAd3-EBO Z
• cAd3 - Recombinant Chimpanzee
Adenovirus Serotype 3 Vectored Ebola
Vaccine
• Non-replicating vector
• Use of chimpanzee adenovirus—little preexisting immunity
• Two types
– Monovalent (Zaire strain)
– Bivalent (Zaire and Sudan strains)
cAd3 vaccine
1. Removal of E1 gene and deletion of E4 gene
2. Insertion of Ebola virus (EBOV) glycoprotein
(EBOV-GP)
3. Transfection of cAd3 genomic plasmid and
expression plasmids in cell culture
4. Production of recombinant adenoviral proteins
Dosage
Dosage
• rVSV – 2x105 PU to 2x107 PU has been seen to
mount a strong immune response in NHP (up to 9
months)
• cAd3
– Monovalent - 1×1010 vp, 2.5×1010 vp, and
5×1010 vp
– Bivalent – 2x1010 PU and 2x1011 PU
• Boosters not possible for cAd3; questionable for
rVSV
• However, a single dose may confer longterm
immunity
The Companies
Who’s working on this?
GSK
• Europe & USA: Have already started trials
on human volunteers
• Vaccine used: ChAd3
• Virus altered: Adenovirus
• Developed by NIAID
Human Efficacy Trials
• Focus countries: Liberia & Sierra Leone
• Guinea also hard-hit, but trials not possible due
to poorly developed infrastructure
• Focus people: Healthcare workers and first-line
responders
• WHO estimate: 12000 healthcare workers,
17500 first-line responders in above three
countries
Human Efficacy Trials
• Liberia: the largest project; 12000
individuals
• Randomised administration:
vaccine/placebo
• Sierra Leone: parallel project; 8000
individuals
• No placebo
• Administered to healthcare workers at
different points in time
NewLink Genetics
• Developed by Public Health Agency of
Canada
• Vaccine used: VSV-EBOV
• Virus modified: Vesicular Stomatitis Virus
• NLG working on human trials
Human Trials
• 40 volunteers planned
• Planned at: Walter Reed Army Institute of
Research & National Institutes of Health
Clinical Center
• Phase 1 in progress
• Determining drug safety and proper dosage
Johnson and Johnson
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In collaboration with Bavarian Nordic
Two-step vaccine
Ready for testing in early 2015
Has been announced only
Crude Cost Estimates
Norwegian Institute of Public Health
27 million doses = $73 million est
Campaigning = $78 million est
NewLink Genetics put in $200 million to
speed up the research
• Could cause another spike in prices due to
competition
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Clinical Trials
Race against time?
Clinical Trials: cAd3-EBO Z
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1st Trial -> August 2014.
2nd Trial -> September 2014.
3rd Trial -> Mali, October 2014
Phase 1 (official title describes it to be in
Phase 1-B)
All studies are in early stages
Clinical Trials: cAd3-EBO Z
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The study that began in August was to see if the
vaccine was safe for humans
2 experimental groups; both given different doses
The study in Mali has begun and 3 people were
infected with vaccine, people in US and 40 people
from Gambia will also be taking part (2
experimental groups with different doses)
The third study from September will have 3 groups
of 20, given different doses
Clinical Trials: VSV-EBOV
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Phase 1 Clinical trial for VSV-EBOV was
launched in US in September
20 vials were sent to US for testing
On October 20th 800-1000 vials were sent to
Geneva along with additional funding
If this phase proves to be successful then the
next phase is to be carried out in west Africa
Results of this trial phase are expected in
December 2014
Clinical Trials: Issues
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Last week of September -> meeting to discuss the best
way to speed up clinical trials and overcome hurdles.
Practical issues that were singled out were:
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Keeping the vaccine at proper temperature
Getting proper staffing and funding
To speed things up they changed study designs and
deployed already available vaccine to workers
Everything said and done—a big enough dose won't be
ready till the first quarter of 2015, and Phase II trials
will also begin around that time.
Questions?
Prepared By GROUP 4
Aizaz Izzat
Ghazia Abbas
Muhammad Hassan Rizvi
Rabia Anjum