Characterisation of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional

Summary: 
      The study will characterise Influenza A/Perth/16/2009(H3N2) virus in healthy participants
      using the viral challenge model. The study includes two cohorts.

      Cohort 1: A randomised, double-blind study of 4 titres of Challenge Virus to determine the
      optimum titre.

      Cohort 2: An open-label extension arm in which all participants will receive the 'optimum'
      titre as identified from Cohort 1.
    

Detailed description: 
      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. Studies using experimental influenza virus infection in human participants have
      demonstrated that adult volunteers can be infected by nasal inoculation, and experimental
      infection is safe and not associated with transmission to contacts. The experimental virus is
      manufactured in compliance with Good Manufacturing Practice for use in the Human Viral
      Challenge Model.

      The investigators chose an H3N2 influenza subtype given that this strain has the most
      substantial impact in terms of morbidity or mortality annually as described by the Centre for
      Disease Control . The investigators first subjected the virus batch to rigorous adventitious
      agent testing, then confirmed the virus to be wild-type by Sanger sequencing and finally
      determined the virus titres appropriate for human use via the established ferret model. hVIVO
      team built on its previous experience with other H3N2 and H1N1 viruses to develop this unique
      model.

      The first part of study (Cohort 1) was to determine the safety and optimal virus titre in
      healthy adult volunteers using our unique clinical quarantine facility in London, UK. After
      the first part of the study was completed, the study was amended to add an older population
      group (45-64 years old) in order to characterise the course of infection in an age group
      better representing the at-risk population.
    

Intervention name(s): Infectious titre 1 (H3N2); Infectious titre 2 (H3N2); Infectious titre 3 (H3N2); Infectious titre 4 (H3N2); Infectious titre 5 (H3N2) (Subjects aged 18 to 45 years old); Infectious titre 5 (H3N2) (Subjects aged 46 to 64 years old)
Intervention type(s): Other; Other; Other; Other; Other; Other
Intervention description(s): Infectious titre 1: 2.8 x 10*3 TCID50/mL; Infectious titre 2: 2.5 x 10*4 TCID50/mL; Infectious titre 3: 3.6 x 10*5 TCID50/mL; Infectious titre 4: 4.7 x 10*6 TCID50/mL; Infectious titre 5: 3.5 x 10*5 TCID50/mL; Infectious titre 5: 3.5 x 10*5 TCID50/mL
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Flu; Influenza; Human Viral Challenge Model; Wild-Type; H3N2; Universal Influenza Vaccine; Intra-seasonal vaccines; Antiviral