Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection
BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.