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Master of Public Health

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

AUTHORS

Ortiz JR , Bernstein DI , Hoft DF , Woods CW , McClain MT , Frey SE , Brady RC , Bryant C , Wegel A , Frenck RW , Walter EB , Abate G , Williams SR , Atmar RL , Keitel WA , Rouphael N , Memoli MJ , Makhene MK , Roberts PC , Neuzil KM , , . The Journal of infectious diseases. 2023 1 26; ().

ABSTRACT

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 through 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 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.

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% CI: 0.62, 1.06; p=0.126) for every two-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.

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