Scientific paper 93 – Use of a Human Influenza Challenge Model to Assess Person-to-Person Transmission: Proof-of-Concept Study

November 7, 2016 3:08 pm

Authors -Ben Killingley,1 Joanne E. Enstone,1 Jane Greatorex,2 Anthony S. Gilbert,3 Rob Lambkin-Williams,3 Simon Cauchemez,4 Jacqueline M. Katz,5 Robert Booy,6 Andrew Hayward,7 John Oxford,8 Carolyn B. Bridges,5 Neil M. Ferguson,4 and Jonathan S. Nguyen Van-Tam1

1 Division of Epidemiology and Public Health, University of Nottingham,

2 Clinical Microbiology and Public Health, Addenbrooke’s Hospital, Cambridge,

3 hVIVO plc formerly Retroscreen Virology Ltd, Queen Mary BioEnterprises, Innovation Centre, London,

4 School of Public Health, Imperial College London, United Kingdom;

5 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia;

6 National Centre for Immunisation Research and Surveillance, Westmead, Australia;

7 Centre for Infectious Disease Epidemiology, University College London,

8 Centre for Infectious Diseases, Bart’s and the London, Queen Mary’s School of Medicine and Dentistry, London, United Kingdom

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Influenza transmission in humans remains poorly understood. In particular, the relative contribution of contact, large droplet, and aerosol transmission is unknown. The aims of this proof-of-concept study were to determine whether an experimentally induced influenza infection is transmissible between humans and whether this would form a viable platform for future studies.


In a quarantine facility, healthy volunteers (‘‘donors’’) were inoculated with A/Wisconsin/67/2005 (H3N2) influenza virus via intranasal drops. On study days 2 and 3 ‘‘recipient’’ volunteers were exposed to donors under close living conditions. Volunteers socialized for 30 hours during a 2-day period. Infection was confirmed by $1 positive results from polymerase chain reaction, virus culture, or serology.


After inoculation, 4 of 9 donors developed symptoms consistent an influenza-like illness (ILI) and 7 of 9 were proven to be influenza-infected. After exposure, 4 of 15 recipients developed symptoms of ILI and 3 of 15 were proven to be infected. Serum collected within 2 days of study initiation indicated that 1 donor and 3 recipients were seropositive at study initiation. After adjustment for preexposure immunity, the overall secondary attack rate was 25% (3 of 12).


Experimental human exposure studies offer an attractive potential method for answering outstanding questions related to influenza transmission and the evaluation of interventions to reduce it.

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