Transcript Dr Roger Gilmour

3rd September 2010
INSERM, Lyon
The Centre for Emergency
Preparedness and Response
Translational Research
Miles Carroll
Director of Research
CEPR
[email protected]
Health Protection Agency
NIBSC
CfI
CEPR
HPA
RMN/LaRs
CRCE
CEPR: Translational Research Activities
Developing Interventions:
UK & Global Public Health
• Safe containment, diagnosis and study of dangerous
pathogens
• Applied research capability including animal facilities
• Development and production of highly specialised biological
products
• Emergency response capability
Working in Partnership with Industry and academia
Translational Research
• Vaccines
• Therapeutics
- Antibiotics/antivirals
- Immunotherapy
- Immune modulation
• Diagnostics
• Decontamination
Developing Interventions for UK Public Health:
In Partnership with Industry and Academia
An Integrated Capability for the
Development of Interventions
Development route is in vitro, in vivo, product development and clinical studies
NVEC
Discovery
Applied research
Development
Translational research
Licensure
Working with Partners to develop interventions.
Past successes: Whooping cough, Menningitis, Anthrax,
Plague, Dysport (cerebral Palsy), Erwinase (childhood
leukaemia treatment, Decontamination products
Translational Research Model
Industry
Vaccine Ags
Vaccine
Discovery
Product
CEPR(HPA)
Chlamydia
US Govt
MCM
Academia/Govt/NforP
HPA plays a pivotal role in development of future health care interventions
Key Research Activities
TB
Toxins
Correlates of
Protection
Vaccines
Antibiotics
Botulinum
Clostridium
Immunotherapy
Diagnostics
Biosafety
Detection
Decontam
HCAI/vCJD
Training
Animal Models
Efficacy studies
Aerosol
Path/ Imaging
SIV
Immune Assay
NVEC
Clinical Trials
Assay Validation
Research
Immune
Modulation
Inflammation
Adjuvants
Emerging
Diseases
Virology
Bacteriology
SPRU Support
Diagnostics
Technology
Diagnostics
Bio/Molecular
Mening &
Pertussis
Correlates
Vaccines
Medical
Counter
Measures
NIAID
Anthrax
Research Aligned with HPA Strategy and Programmes
Developing Interventions for Emerging Diseases
& Bio-threat Agents
Tradition route is in vitro, then human Phase 1, 2 and then Phase 3 trials
Discovery
Pure research
Development
Translational research
Licensure
Traditional clinical efficacy trials not possible with diseases
like Anthrax, Plague, Meliodosis, Glanders and Ebola
The FDAs “Animals Rule” provides an alternative where
Efficacy in 2 animal models may be accepted for licensure
The NIAID Programme at HPA CEPR
Anthrax in mice and NHPs (C1, D1)
Plague in mice (C18)
Q fever in mice (C19)
Melioidosis in mice (C19)
Filoviruses (C20)
Antibiotics, small molecules
& therapies
(A1, B1)
Discovery
Pure research
Vaccines
Development
Translational research
Anthrax in NHPs (D1)
Melioidosis in NHPs (D19)
Glanders in NHPs (D19)
Flu (E10)
Multiple agents in NHPs (D8, Dstl)
Monkeypox in NHPs (D4/D7, D18,
E07)
Licensure
Animal Models: Development of New
Interventions for Infectious Diseases
Development & evaluation of vaccines, therapeutics and diagnostics
• Easily Transmitted
• High mortality
• Limited / no treatment
High consequence pathogens Surveillance and development
of interventions
Viral Hemorrhagic Fevers:
Bacterial infections:
1% / 20%
~40%
Cutaneous Anthrax Inhalation Anthrax
5% / 90%
Pneumonic plague
30 - 80%
CCHF
Ebola
1% / 60%
Bubonic plague
50 - 95%
Viral infections:
Lassa fever
Dengue (HF)
Approximate
30 - 60%
Orthopox
<20%
<20%
mortality rates
High Consequence Pathogen Studies
Remit:
Responsible for maintaining research and development
programmes concerned with viral haemorrhagic fevers
and arboviruses in line with the department’s capacity
as a HPA reference centre and WHO collaborating
centre for virus research and reference.
Reduce the impact of new and re-emerging health
threats and help manage UK health protection
emergencies through effective early detection and
response.
Special Pathogens Reference Unit
Virus Reference service:
• Arboviruses
“To reduce the impact of
new and re-emerging
threats and manage UK
Flaviviridae
Virus research
programme
health protection
Bunyaviridae
provides ready toemergencies
action relevant
through
Togaviridae
effective capacity
early detection
skills and knowledge
to and
response”
Reoviridae
rapidly respond to new
virus
•
threats (c.f. expertise of virology
Haemorrhagic
Fever flu
viruses
staff to pandemic
activities)
Filoviridae
Arenaviridae
Others
• Orthopoxvirus
• Hantavirus
• Henipaviruses
“Work on high
consequence pathogens
through WHO
international
collaborations to build
preparedness to
infectious disease
threats”
Current virology projects
Programme built around GIA
Euro-P4
FP7
Georgia SC
DTRA / UK
DTRA
Ebola model
Surveillance
Understanding viruses
Japan-P4
Outputs:
• Assay development / validation
• Direct patient monitoring
• Assay roll out to global partners
• Underpinning Knowledge
• Training & Knowledge transfer
• Work at high containment (CL4)
• Scientific reputation
• Travel advice
“To reduce the impact of new and
re-emerging threats and manage
UK health protection emergencies
through effective early detection
and response”
Infrastructure
GIA
Epidemiology
GIA
Arbo / VHF
NIAID
Filovirus reagents
“Strengthening public
health capacity re better
diagnostics and
response”
“Building similar capacities in
partner / collaborating countries
leading to better preparedness
to new and re-emerging
threats”
Translational Research Activities
Product
Therapeutics
C.difficile
TB
Sepsis
MCM
Vaccines
Chlamydia
Meningitis
Pertussis
MCM
TB
Emerging Dis
Influenza
Diagnostics
MCM Pathogens
HCAI Diagnostics
vCJD Blood
Emerging Dis
Radiation
Research
Development Clinical
The Centre for
Emergency Preparedness and Response
Miles Carroll
Deputy Director
Head of Research
Understanding Pathogenesis and
Disease Kinetics: H1N1
Low dose (approx 10E2)
Intermediate dose (approx 10E4)
High dose (approx 10E6)
TCID50/ml (log 10)
7
6
5
4
3
2
0
1
2
3
4
5
Time post-challenge (days)
6
7
Nasal wash - viral load TCID50
Developed for Evaluation of swine flu vaccines
Influenza Animal Models:
How Realistic Are They?
Natural infection - dose ≈ 0.6 – 3.0 pfu
6
Ferret model – dose = 10 pfu
Human disease kinetics:incubation period 2-7 days for H1N1.
Would lower dose effect disease kinetics and pathogenesis?
Increased sensitivity for evaluation of vaccines and therapeutics