A Multicenter, Controlled Human Infection Study of Influenza A(H1N1)pdm09 in Healthy Adults
Jan-23
Journal Article
Authors:
Volume:
228
Pagination:
287-298
Issue:
3
Journal:
J Infect Dis
PMID:
36702771
URL:
https://www.ncbi.nlm.nih.gov/pubmed/36702771
Keywords:
Humans Adult *Influenza, Human/prevention & control *Influenza A Virus, H1N1 Subtype Antibodies, Viral Research Design Hemagglutination Inhibition Tests *Influenza Vaccines H1N1 subtype clinical trial human influenza influenza A virus
Abstract:
<p>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. Clinical Trials Registration. NCT04044352.</p>