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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