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Published: 26 January 2023
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.
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.