More Related Content Similar to Innate response targets for therapy CDE themed competition launch (20) More from 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
UNCLASSIFIED© Crown copyright 2014 Dstl
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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
UNCLASSIFIED© Crown copyright 2014 Dstl
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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
UNCLASSIFIED© Crown copyright 2014 Dstl
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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
UNCLASSIFIED© Crown copyright 2014 Dstl
31 March 2014
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
31 March 2014
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
© Crown copyright 2014 Dstl
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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
31 March 2014
© Crown copyright 2014 Dstl
42. Challenge 1
© Crown copyright 2014 Dstl
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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
© Crown copyright 2014 Dstl
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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
31 March 2014
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
© Crown copyright 2014 Dstl
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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
© Crown copyright 2014 Dstl
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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
31 March 2014
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
© Crown copyright 2014 Dstl
31 March 2014
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
31 March 2014
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
31 March 2014
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
31 March 2014
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