MS Porton Down Microbiology & Translational Research Mission - - PowerPoint PPT Presentation

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MS Porton Down Microbiology & Translational Research Mission - - PowerPoint PPT Presentation

Apr 30, 2023 32 likes •145 views

MS Porton Down Microbiology & Translational Research Mission Public Health England To protect and improve the nations health and to address inequalities, working with national and local government, the NHS, industry, academia,

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MS Porton Down

Microbiology & Translational Research Mission – Public Health England

“To protect and improve the nation’s health and to address inequalities, working with national and local government, the NHS, industry, academia, the public and the voluntary and community sector.” Phil Marsh

  • n behalf of Miles Carroll
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SLIDE 2

PHE - Porton

  • emergency response capability
  • high containment of

pathogenic agents [CL2-CL4]

  • diagnostic capabilities [RIPL]
  • culture collection (CC of PHE)
  • developmental production
  • biopharmaceutical manufacture
  • translational research
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SLIDE 3

Discovery Development Licensure Applied research Translational research

An Integrated Capability for the Development of Interventions

Development route is in vitro, in vivo, product development and clinical studies

Working with Partners to develop interventions. Past successes: Whooping cough, Meningitis, Anthrax, Plague, Dysport (cerebral Palsy), Erwinase (childhood leukaemia treatment, Decontamination products

NVEC

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SLIDE 4

Infectious Disease Programmes

Research

Mening & Pertussis

Correlates Vaccines

TB

Vaccines Antibiotics Diagnostics

Diagnostics Technology

Diagnostics Bio/Molecular

Toxins

Botulinum Clostridium Immunotherapy Diagnostics

Medical Counter Measures

NIAID Anthrax

Immune Modulation

Inflammation Adjuvants GxP

Immune Assay Clinical Trials Assay Validation Product release assays

Preclinical

Efficacy studies Aerosol Pathol/ Imaging Immunology

Developing Interventions with academia, Govt and industry Emerging Diseases

Virology/Influenza Bacteriology

Biosafety

Detection Decontam HCAI/vCJD Training

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SLIDE 5

rpm

Medium

Capabilities - Chemostat

 Continuous culture device  Controlled and defined environment  Select a “growth-limiting” nutrient  Constant growth rate for prolonged periods - steady state  Defined, physiological state  Vary individual parameters  Direct cause-and-effect relationships  Expression profiles are reproducible

pH

O2

Biomass

C

Pure culture:  Neisseria gonorrhoeae  Legionella pneumophila  Salmonella enteritidis  oral opportunitic pathogens  Mycobacterium tuberculosis / M. bovis Conditions:

  • Carbon limitation
  • Nitrogen limitation
  • Iron limitation
  • Growth temperature
  • Growth rate
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Application of chemostats to drug evaluation

  • 96 well plate
  • Drug combinations
  • Fluorescent stain
  • Fix
  • Flow cytometry

Host-like conditions Slow growth Stationary phase Reproducible source of cells

Defined populations:

  • Live
  • Dead
  • Persistent

O2 pH

Development of a rapid assay Definition of live, dead, and drug tolerant (persisting) bacteria Fluorescence stains and flow cytometry

10 20 30 40 50 60 70 80 90 100 Day 0 Day 1 Day 2 Day 3 Day 4 1.00E+00 1.00E+01 1.00E+02 1.00E+03 1.00E+04 1.00E+05 1.00E+06 1.00E+07 1.00E+08 Day 0 Day 1 Day 2 Day 3 Day 4 cfu/ml

INH TVCs

0 ug/ml 0.25 ug/ml 0.5 ug/ml 1 ug/ml 2 ug/ml 4 ug/ml 8 ug/ml 16 ug/ml 32 ug/ml

A C B

INH

s

0 ug/ml 0.25 ug/ml 0.5 ug/ml 1 ug/ml 2 ug/ml 4 ug/ml 8 ug/ml 16 ug/ml 32 ug/ml INH 0.5 µg/ml INH No drug 8 µg/ml INH 16 µg/ml INH % of events in gate R5 (CV+SG-)

DAY 0 - No drug DAY 04

FL6 log FL1 log FL6 log FL6 log FL6 log FL1 log FL1 log FL1 log FL6 log FL1 log R3 R2 R3 R4 R5 R4 R5 R4 R5 R4 R5 R2 R3 R2 R3 R2 R3 R4 R5 R2

CL3 cell sorting:

  • defined bacterial populations for

further analyses

Biofilm models

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SLIDE 7

Preclinical testing at Porton Down

  • Range of models.
  • Immunogenicity and challenge studies.
  • ACDP3 containment facilities: in vitro,

in vivo, ex vivo studies.

  • Large capability

(largest TB vaccine evaluator in Europe – small animal models).

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SLIDE 8

Aerosol Generation

  • Nebulisers generate particles in respirable range

<5 µm.

  • Henderson Apparatus controlled by Aero-MP

(relative humidity, flow rates, exposure times, suspending fluid).

  • Directional flow systems -

(bespoke ‘sow’ system or individual mask).

  • Plethysmography equipment.
  • Reproducible, low dose (5-10 cfu),

even distribution.

Aerobiology expertise

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National & International Reference Centre

  • Haemorrhagic Fever viruses

Filoviridae Arenaviridae

  • Arboviruses

Flaviviridae Bunyaviridae Togaviridae Reoviridae

  • Orthopoxviruses
  • Hantaviruses
  • Henipaviruses

WHO Collaborative Centre for Viruses (Arboviruses & VHFs) Porton Down 1976

Flexible film isolator with computer controlled exposure system

9 In vitro and in vivo R&D at high containment; PHE Porton

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SLIDE 10

Translational R&D

New antigens:

  • meningitis
  • TB
  • anthrax
  • C. difficile

Correlates of protection:

  • meningitis
  • pertussis
  • TB

Evaluation [clinical trials]:

  • NVEC
  • grants
  • commercial

Evaluation in preclinical models: [drugs, vaccines, etc]

  • medical counter-measures
  • TB
  • ‘flu
  • ......& many others....

PHE Porton: Unique Translational Research Capability

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SLIDE 11

Translational Research Model

PHE Discovery Product Industry Academia/Govt/NforP

PHE plays a pivotal role in translating Research into future health care interventions