A Multicenter, Controlled Human Infection Study of Influenza A(H1N1)pdm09 in Healthy Adults
01/2023
Journal Article
Authors:
Ortiz, J. R.;
Bernstein, D. I.;
Hoft, D. F.;
Woods, C. W.;
McClain, M. T.;
Frey, S. E.;
Brady, R. C.;
Bryant, C.;
Wegel, A.;
Frenck, R. W.;
Walter, E. B.;
Abate, G.;
Williams, S. R.;
Atmar, R. L.;
Keitel, W. A.;
Rouphael, N.;
Memoli, M. J.;
Makhene, M. K.;
Roberts, P. C.;
Neuzil, K. M.
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:
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.
