A Multicenter, Controlled Human Infection Study of Influenza A(H1N1)pdm09 in Healthy Adults

Background We evaluated the associations between baseline influenza virus-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers and subsequent symptomatic influenza virus infection in a controlled human infection study. Methods We inoculated unvaccinated healthy adults aged 18-49 years with an influenza A/California/04/2009/H1N1pdm-like virus (NCT04044352). We collected serial safety labs, serum for HAI and MN, and nasopharyngeal swabs for reverse-transcription polymerase chain reaction (RT-PCR) testing. Analyses used the putative seroprotective titer of >= 40 for HAI and MN. The primary clinical outcome was mild-to-moderate influenza disease (MMID), defined as >= 1 postchallenge positive qualitative RT-PCR test with a qualifying symptom/clinical finding. Results Of 76 participants given influenza virus challenge, 54 (71.1%) experienced MMID. Clinical illness was generally very mild. MMID attack rates among participants with baseline titers >= 40 by HAI and MN were 64.9% and 67.9%, respectively, while MMID attack rates among participants with baseline titers <40 by HAI and MN were 76.9% and 78.3%, respectively. The estimated odds of developing MMID decreased by 19% (odds ratio, 0.81 [95% confidence interval, .62-1.06]; P = .126) for every 2-fold increase in baseline HAI. There were no significant adverse events. Conclusions We achieved a 71.1% attack rate of MMID. High baseline HAI and MN were associated with protection from illness. In a multicenter controlled human infection model study, we inoculated 76 participants with influenza A/California/04/2009/H1N1pdm-like virus and safely achieved a 71.1% attack rate of mild-to-moderate influenza disease. High virus-specific hemagglutination inhibition and microneutralization titers were associated with protection from illness.