title: Accelerating Influenza Research: Vaccines, Antivirals, Immunomodulators and Monoclonal Antibodies. The Manufacture of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model.
abstract: BACKGROUND
  Influenza and its associated diseases are a major cause of morbidity and mortality. The United States Advisory Committee on Immunization Practices recommends influenza vaccination for everyone over 6 months of age. The failure of the flu vaccine in 2014-2015 demonstrates the need for a model that allows the rapid development of novel antivirals, universal/intra-seasonal vaccines, immunomodulators, monoclonal antibodies and other novel treatments. To this end we manufactured a new H3N2 influenza virus in compliance with Good Manufacturing Practice for use in the Human Viral Challenge Model.
  We chose an H3N2 influenza subtype, rather than H1N1, given that this strain has the most substantial impact in terms of morbidity or mortality annually as described by the Centre for Disease Control. We first subjected the virus batch to rigorous adventitious agent testing, confirmed the virus to be wild-type by Sanger sequencing and determined the virus titres appropriate for human use via the established ferret model. We built on our previous experience with other H3N2 and H1N1 viruses to develop this unique model.
  We conducted an initial safety and characterisation study in healthy adult volunteers, utilising our unique clinical quarantine facility in London, UK. In this study we demonstrated this new influenza (H3N2) challenge virus to be both safe and pathogenic with an appropriate level of disease in volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we established the minimum infectious titre required to achieve reproducible disease whilst ensuring a sensitive model that can be translated to design of subsequent field based studies.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02525055.
authors.affiliation: hVIVO Services Limited, Queen Mary BioEnterprises Innovation Centre, 42 New Rd, London, E1 2AX, England, United Kingdom.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Fullen
authors.affiliation: hVIVO Services Limited, Queen Mary BioEnterprises Innovation Centre, 42 New Rd, London, E1 2AX, England, United Kingdom.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Noulin
authors.affiliation: hVIVO Services Limited, Queen Mary BioEnterprises Innovation Centre, 42 New Rd, London, E1 2AX, England, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Catchpole
authors.affiliation: hVIVO Services Limited, Queen Mary BioEnterprises Innovation Centre, 42 New Rd, London, E1 2AX, England, United Kingdom.
authors.forename: Hosnieh
authors.initials: H
authors.lastname: Fathi
authors.affiliation: hVIVO Services Limited, Queen Mary BioEnterprises Innovation Centre, 42 New Rd, London, E1 2AX, England, United Kingdom.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Murray
authors.affiliation: hVIVO Services Limited, Queen Mary BioEnterprises Innovation Centre, 42 New Rd, London, E1 2AX, England, United Kingdom.
authors.forename: Alex
authors.initials: A
authors.lastname: Mann
authors.affiliation: hVIVO Services Limited, Queen Mary BioEnterprises Innovation Centre, 42 New Rd, London, E1 2AX, England, United Kingdom.
authors.forename: Kingsley
authors.initials: K
authors.lastname: Eze
authors.affiliation: hVIVO Services Limited, Queen Mary BioEnterprises Innovation Centre, 42 New Rd, London, E1 2AX, England, United Kingdom.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Balaratnam
authors.affiliation: hVIVO Services Limited, Queen Mary BioEnterprises Innovation Centre, 42 New Rd, London, E1 2AX, England, United Kingdom.
authors.forename: Daryl W
authors.initials: DW
authors.lastname: Borley
authors.affiliation: hVIVO Services Limited, Queen Mary BioEnterprises Innovation Centre, 42 New Rd, London, E1 2AX, England, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gilbert
authors.affiliation: hVIVO Services Limited, Queen Mary BioEnterprises Innovation Centre, 42 New Rd, London, E1 2AX, England, United Kingdom.
authors.forename: Rob
authors.initials: R
authors.lastname: Lambkin-Williams
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000737:chemistry; D004311:Double-Blind Method; D005260:Female; D005289:Ferrets; D064368:Healthy Volunteers; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics*; D007252:Influenza Vaccines / Q000737:chemistry / Q000627:therapeutic use*; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D008131:London; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017201:Virus Shedding; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000998:Antiviral Agents; D007252:Influenza Vaccines