A Multicenter, Controlled Human Infection Study of Influenza A(H1N1)pdm09 in Healthy Adults

Authors

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
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

Publication Date

8-11-2023

Journal

The Journal of Infectious Diseases

DOI

10.1093/infdis/jiad021

PMID

36702771

PMCID

PMC10420403

PubMedCentral® Posted Date

1-26-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Adult, Influenza, Human, 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 titers76.9% 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.

Comments

Clinical Trials Registration. NCT04044352.

Associated Data