Contenu connexe Similaire à Innate response targets for therapy CDE themed competition launch (20) Plus de Defence and Security Accelerator (20) Innate response targets for therapy CDE themed competition launch7. Scope
• Mission
• Future Force 2020
• CBRN protection requirement
– Threat
– Policy
• CBRN programme
– Policy
– CBR protection
– Current capabilities and challenges
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8. Defence in a changing world
Defence’s mission:
To protect our country and
guarantee its security and independence
UNCLASSIFIED© Crown copyright 2014 Dstl
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Source: Defence Transformation
9. FF 2020
• Significant Defence reform
– Post Afghanistan Contingency
– ‘Carter’s circles’
– FF 2020 structure
– Budget c.£36Bn pa
– Manpower: c.175k
• Navy c.30k
• Army c.82k + 30k
• RAF c.33k
Homeland
Defence
Force
Projection
Defence
Engagement
UNCLASSIFIED© Crown copyright 2014 Dstl
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Source: Defence Transformation
11. UNCLASSIFIED© Crown copyright 2014 Dstl
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CBR Protection Requirement
(Threat)
State Threat
Lone Wolf Threat Industrial Threat
Terrorist Threat
Source: Open source
12. CBR Protection Requirement
(Threat - 2)
Nervous system
• Nerve agents
• Toxins
Lung
• Sulphur mustard
• Phosgene
• Toxic industrial
chemicals
Skin
• Sulphur mustard
• Nitrogen mustard
• Toxic industrial
chemicals
Multiple
targets
• Ionising
radiation
• Biological
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13. • Hazard area
• ‘Detect to treat’
CBR Protection Requirement
(Threat - 3)
UNCLASSIFIED© Crown copyright 2014 Dstl
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Source: Open source
14. CBRN Protection Requirement
(Policy)
Prevention of
Supply
ProtectionElimination
Arms
Control
Disablement
Deterrence
Cooperative Non-Cooperative
UK CBRN Protection Policy: Armed Forces should be able to “Survive and
Operate” in all CBRN environments
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21. • Way forward?
– A variety of projects are underway to improve our capability
– There is a plan
– Some funding has been allocated
CBRN Protection Requirement
(Capability - 7)
UNCLASSIFIED© Crown copyright 2014 Dstl
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22. Summary
• Defence Reform – FF 2020
• Evolving threat – State and non-state
• Policy challenges
– Bio: ‘Detect to treat’
– ‘Survive and operate in all CBRN environments’ is difficult
• CBRN Protection capabilities are beginning to get the
investment they need
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24. UNCLASSIFIED
Biological Agents
• Very low infectious dose
– Highly toxic
• Infectious via the inhalational route
• Cause endemic disease
• Usually zoonotic diseases
• Lethal or incapacitating
• BTWC has no schedules and no verification regime
28. UNCLASSIFIED
Regulations and Best Practise
• Dangerous Pathogens work conducted in accordance
with Health and Safety Executive
(ACDP/ACGM/COSHH) and DEFRA guidelines
• Animal studies conducted under licence by the Home
Office
29. UNCLASSIFIED
Vaccination
• Name derived from use of cowpox (Vaccinia) to protect against
smallpox
– Jenner 1796
– Pasteur 1881
• Suspension of dead, attenuated or otherwise modified micro-
organisms USED TO INDUCE IMMUNITY TO A DISEASE
– Stimulates immune system (e.g. antibodies)
– Induces memory
– Eradicates disease
The most cost effect way to treat infectious disease
30. UNCLASSIFIED
Time (days)
Percentsurvival
0 7 14 21 28
0
20
40
60
80
100
Conjugate
LPS
TetHc + LPS
PBS
TetHc
Bacteria(cfu/spleen)
Conjugate
LPS
TetHc + LPS
PBS
TetHc
10
100
1000
10000
100000
1000000
P<0.001
Exp.1
Exp.2
Exp.1
Exp.2
Exp.1
Exp.2
Exp.1
Exp.2
Exp.1
Exp.2
Conjugate
LPS
TetHc + LPS
PBS
TetHc
Burkholderia and Francisella vaccines
31. UNCLASSIFIED
Antibiotics
• Not active against some bacteria
– Natural resistance
• Different antibiotics required for different agents
• Relapsing infection
• Trigger to treat required
• Compliance/Side effects
– 44% completed 60 day course during BA letter attacks
BUT
• Broad spectrum of activity
• No predefined threat spectrum
32. UNCLASSIFIED
CFI is a broad spectrum antibiotic effective
against multiple BW agents
• Treatment with encapsulated
ciprofloxacin effectively treats three
BW agents: F. tularensis, Y. pestis
and C. burnetii
• In collaboration with Health
Protection Agency, Defence
Research and Development
Canada and Aradigm Corporation
33. UNCLASSIFIED
Humanised Antibody for the Treatment of Venezuelan
Equine Encephalitis Virus (VEEV)
• No available licensed vaccines or
antivirals for treatment of VEEV
• A mouse monoclonal antibody is
effective for the treatment of
VEEV in a mouse model of
disease
• Humanised antibody produced to
reduce potential adverse
reactions in humans
– biologically active
– protects mice against lethal
VEEV challenge
0 5 25 50 75 100
0
20
40
60
80
100
Antibody (μg) Administered
PercentSurvival
Survival of BALB/c mice pre-treated with humanised
antibody before challenge with 100LD50 of VEEV
O'Brien LM et al, Virology. 2012,
Goodchild SA, et al, Antiviral Res. 2011
34. UNCLASSIFIED
Summary
• A flexible response is essential
• Vaccines provide excellent protection for those
immunised before exposure
• Post-exposure therapies provide a rapid response
capability against some agents
• Following a BW attack, and for some agents, it will be
necessary to use both post-exposure therapies and
vaccines
36. Key dates
• Competition launches today
• Presentation to follow
• Opportunity for Q&A
• Webinar Tuesday 1 April
• Deadline for applications Thursday 5 June 2014 at 17:00 hrs
via Centre for Defence Enterprise Portal
• Funding decisions to be made July 2014
• Notifications end July
© Crown copyright 2014 Dstl
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37. Background: biothreat agents
• Pathogenic for man or animals
• Very low infectious dose
• Infectious via the inhalational route
• Cause endemic disease around world
• Usually are zoonotic diseases
• Lethal or incapacitating
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38. © Crown copyright 2014 Dstl
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Defence against biothreats
• Many potential biothreat agents
• How to defend against them?
• Impossible to make a vaccine/therapy for every
potential agent
• Require generic therapy
39. Generic approach to therapy
• By influencing the host response
• Requires an understanding of the host response to pathogen & safe
ways to influence it
• Requires identification of relevant targets or pathways in the host
31 March 2014
© Crown copyright 2014 Dstl
40. Innate (host) response targets for therapy
• Objective of this competition is to look broadly across research and
development to identify host cell targets and pathways
• Using data derived from diverse infection models
• Respondents to competition do not need to work directly with
biothreat agents
• Ultimate aim is to apply the most innovative approaches to biothreat
agents
31 March 2014
© Crown copyright 2014 Dstl
41. CDE themed competition specifics
• Seeking innovative proposals for short projects (<1year); £30-
80k guide; (£500k total budget)
• Show proof-of-concept for your proposal; there is funding
allocated for follow-on work for successful projects
• Competition divided into 3 challenges
• Respondents need to address 1 of the challenges, may address
>1, do not have to address all 3
• Challenges described fully in the competition document
• Bids must be ethical and compliant with UK government
legislation
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© Crown copyright 2014 Dstl
42. Challenge 1
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Identification of new cellular or host pathway targets
43. Identification of new cellular or host pathway
targets
• In host-pathogen model of your choice
– Does not need to be a biodefence pathogen
– Does not need to be in vivo
• Conditioning of cells ex vivo
eg to profile responses or prior to adoptive transfer
• Targeting cells in situ eg
– to refocus them
– to activate them
– to induce them to traffic
– to redirect them
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44. Identification of new cellular or host pathway
targets
May involve the identification of eg
• immuno stimulants
• modulators
• transfection factors
• chemokines, cytokines
or the induction (or blockade) of these
• cytokine/chemokine/growth factor receptors
and application of these to modulate host
responses
© Crown copyright 2014 Dstl
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45. Identification of new cellular or host pathway
targets
• Some of these may be
exogenous and some
endogenous factors
• Some endogenous natural
regulators /regulatory
pathways may be exploited
• to reduce inflammation
and to restore homeostasis
© Crown copyright 2014 Dstl
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Normal
OveractiveUnderactive
46. Possible outcomes
Proposals for
– identification of new cellular targets /pathways
– new applications of manipulating known cellular targets/pathways
– demonstration that targets may be influenced beneficially, for
example to:
• prevent cytotoxicity
• prevent/reduce microbial invasion
• reduce microbial load
• restore normal cell function
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48. Identification of new candidate therapies
Exploit appropriate cellular targets and pathways to
identify new therapies by, for example:
• enhancing cell-mediated immunity
• investigating novel combinations
• identification and manipulation of significant
transcription factors
• micro RNA-directed therapies or antagonists
© Crown copyright 2014 Dstl
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49. Possible outcomes
• Candidate therapies should be druggable and generic
• Proposals should show proof-of-concept
• Does not exclude the re-purposing or augmentation of existing
therapies
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51. Identification of new platform technologies
For assessing therapeutic benefit
• Novel technologies such as:
• non-invasive methods of in-vivo/ex-vivo
analysis eg bio-imaging or tracking
• Transcriptomics including micro RNA analysis
• In-silico modelling of host responses
• Novel assays to monitor the host immune response
© Crown copyright 2014 Dstl
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52. Possible outcomes
• New technologies which may facilitate the identification and
development of candidate therapies
• Proposals should demonstrate the impact of the technology
on therapeutic development
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53. What we want
• Highly innovative approaches that are significantly different from
existing technologies
• Generally technology readiness level (TRL) ≤ 3
• Generic approaches (not pathogen specific)
• Approaches applicable to intracellular pathogens where
appropriate
• Approaches that will lead to a feasible clinical product
© Crown copyright 2014 Dstl
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54. What we don’t want
Proposals that concern:
• high technology readiness level (TRL) capability
• serological targets only (rather than cellular)
• antibody-based therapies (but antibodies as a targeting
mechanism are acceptable)
• existing solutions or technology already tested and found to
have limited utility
• a paper study or review or similar
• pre-exposure therapies or therapeutics
• topical therapies for wounds
© Crown copyright 2014 Dstl
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55. Successful proposals
• Each will be assigned a Technical Partner
– Provides interface between project and defence community
– If project successful, potential routes to exploitation
developed
© Crown copyright 2014 Dstl
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56. Summary
• Competition launches today
• Webinar Tuesday 1 April
• Closes on Thursday 5 June 2014 at 17:00 hrs
• Short proof-of-concept proposals
• If successful, potential for follow-on funding
• May include additional research to develop technology for MOD
• Competition information available on CDE website
www.science.mod.uk
© Crown copyright 2014 Dstl
31 March 2014