title: Characterisation of a wild-type influenza (A/H1N1) virus strain as an experimental challenge agent in humans.
abstract: BACKGROUND
  Human challenge models using respiratory viruses such as influenza are increasingly utilised in the development of novel vaccines and anti-viral modalities and can provide preliminary evidence of protection before evaluation in field trials. We describe the results of a clinical study characterising an A/H1N1 influenza challenge virus in humans.
  
  
  METHODS
  The challenge agent, influenza A/California/2009 (H1N1), was manufactured under cGMP conditions and characterised in accordance with regulatory guidelines. A dose-ascending open-label clinical study was conducted in 29 healthy young adults screened sero-negative to the challenge strain. Subjects were intranasally inoculated with three increasing doses of virus and physician-reported signs, subjected-reported symptoms, viral shedding and immunological responses were monitored.
  
  
  RESULTS
  A dose-dependent increase in clinical signs and symptoms was observed with 75% of subjects developing laboratory-confirmed illness at the highest inoculum (3.5 × 10(6) TCID50). At the highest dose, physician or subject-reported signs of infection were classified as mild (all subjects), moderate (50%) and severe (16%) with peak symptoms recorded four days after infection. Clinical signs were correlated with nasal mucus weight (P < .001) and subject-reported symptoms (P < .001). Geometric mean peak viral shedding was log10 5.16 TCID50 and occurred three days after inoculation with a median duration of five days. The safety profile was such that physiological responses to viral infection were mainly restricted to the upper airways but were not of such severity to be of clinical concern.
  
  
  CONCLUSIONS
  A highly characterised wild-type Influenza A/California/2009 (H1N1) virus manufactured for clinical use was shown to induce a good infectivity profile in human volunteers. This clinical challenge model can be used for evaluating potential efficacy of vaccines and anti-viral therapeutics.
  
  
  BACKGROUND
  NCT02014870.
authors: Immune Targeting Systems Ltd, London BioScience Innovation Centre, 2 Royal College Street, London, NW1 0NH, UK. jeannette.watson@its-innovation.com.
authors: Jeannette M
authors: JM
authors: Watson
authors: Immune Targeting Systems Ltd, London BioScience Innovation Centre, 2 Royal College Street, London, NW1 0NH, UK. james.francis@its-innovation.com.
authors: James N
authors: JN
authors: Francis
authors: SGS LSS, Clinical Research Unit, Antwerpen, Belgium. sofie.mesens@sgs.com.
authors: Sofie
authors: S
authors: Mesens
authors: Immune Targeting Systems Ltd, London BioScience Innovation Centre, 2 Royal College Street, London, NW1 0NH, UK. gabriel.faiman@its-innovation.com.
authors: Gabriel A
authors: GA
authors: Faiman
authors: Jill Makin Consulting Ltd, 7 Cholmondeley Road, West Kirby, Wirral, CH48 7HB, UK. jill@jillmakinconsulting.co.uk.
authors: Jill
authors: J
authors: Makin
authors: Biologics Consulting Group, INC, 1317 King Street, Alexandria, VA, 22314, USA. ppatriarca@bcg-usa.com.
authors: Peter
authors: P
authors: Patriarca
authors: University of Rochester Medical Center, 601 Elmwood Avenue, Box 689, Rochester, NY, 14642, USA. John_Treanor@URMC.Rochester.edu.
authors: John J
authors: JJ
authors: Treanor
authors: Immune Targeting Systems Ltd, London BioScience Innovation Centre, 2 Royal College Street, London, NW1 0NH, UK. bertrand.georges@its-innovation.com.
authors: Bertrand
authors: B
authors: Georges
authors: Immune Targeting Systems Ltd, London BioScience Innovation Centre, 2 Royal College Street, London, NW1 0NH, UK. campbell.bunce@its-innovation.com.
authors: Campbell J
authors: CJ
authors: Bunce
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000302:isolation & purification / Q000627:therapeutic use; D002675:Child, Preschool; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000502:physiology*; D007252:Influenza Vaccines / Q000276:immunology / Q000302:isolation & purification; D007251:Influenza, Human / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D036302:Therapeutic Human Experimentation; D017201:Virus Shedding; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D007252:Influenza Vaccines
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