A Multi-Center, Controlled Human Infection Study of Influenza A (H1N1)pdm09 in Healthy Adults

ABSTRACT Background Influenza controlled human infection model (CHIM) studies can advance development of vaccines and therapeutics. Our objective was to evaluate the associations between baseline challenge virus-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers and subsequent symptomatic influenza virus infection. Methods We enrolled healthy adults aged 18 through 49 years in a multisite CHIM study using influenza A/Bethesda/MM2/H1N1, an A/California/04/2009/H1N1pdm-like virus ( NCT04044352 ). We excluded persons vaccinated against influenza within the previous six months. We collected serial safety labs, serum for HAI and MN, and nasopharyngeal swabs for 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 post-challenge positive qualitative RT-PCR test with a qualifying symptom/clinical finding. Findings Of 76 participants given influenza virus challenge, 54 (71.1%) experienced MMID. Clinical illness post-challenge 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% CI: 0.62, 1.06; p=0.126) for every two-fold increase in baseline HAI. There were no deaths, serious adverse events, or other significant adverse events. Interpretation In a multi-site influenza CHIM study, we assured the safety of our participants and achieved a 71.1% attack rate of MMID. High baseline HAI and MN were associated with protection from illness.