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

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

    Published: 26 January 2023

    https://doi.org/10.1093/infdis/jiad021

    Justin R Ortiz, David I Bernstein, Daniel F Hoft, Christopher W Woods, Micah T McClain, Sharon E Frey, Rebecca C Brady, Christopher Bryant, Ashley Wegel, Robert W Frenck, Jr.,
    Emmanuel B Walter, Getahun Abate, Sarah R Williams, Robert L Atmar, Wendy A Keitel, Nadine Rouphael, Mathew J Memoli, Mamodikoe K Makhene, Paul C Roberts, Kathleen M Neuzil


    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.

    https://watermark.silverchair.com/ji...RIlvRceLsAvs-c
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