Human challenge studies in healthy volunteers: practical considerations and outcomes of influenza trials
-
1
SGS Belgium NV, Clinical Pharmacology Unit Antwerpen, Belgium
Background: Influenza challenge studies in healthy volunteers aim at disease modelling in strictly-regulated and controlled
conditions, and testing novel antiviral/anti-inflammatory therapies. An optimal human model requires a virulent species with
high infectivity, relevant symptoms without safety concerns, as well as optimal methods for virus preparation, inoculation,
sample management and data analysis. We report our experience with influenza trials at our clinical site.
Methods: Our challenge models included influenza A subtypes H1N1 and H3N2, inoculated (0.25 mL per nostril) with a pipette or
a VaxINator device respectively. Immunity to influenza was assessed by hemagglunitation-inhibition (HAI) or microneutralisation
(MNT) assays, and adventitious agents in the airways were screened using semi-quantitative PCR1. Influenza-like illness (ILI) was
monitored twice daily using a 35-questions symptoms scorecard (SSC)2, qPCR and tissue culture.
Results: Subjects’ selection strategy was crucial, with 29% (MNT) to 58% (HAI) volunteers being excluded for immunity to
influenza and 12-13% for abnormal spirometry records. Inoculation with VaxINator device, which produces a spray of challenge
agent in the airways, was much appreciated by the operational team. The SSC showed a dose-dependent ILI between 3 to 5
days post-inoculation, and this pattern correlated with viral shedding in the three dose groups (H3N2) or in the treated versus
placebo groups (H1N1) as assessed by qPCR and viral culture.
Conclusion: Human challenge studies are intensive processes requiring close monitoring and optimal techniques to deliver
reliable data. Our influenza H1N1 and H3N2 challenge studies provided expected outcomes while following standardized
methods. Another H3N2 interventional study is currently in recruitment phase.
References:
1 Ruggiero P., McMillen T., Tang Y., Babady N.E. Evaluation of the BioFire Film Assay Respiratory Panel and the GenMark eSensor
Respiratory Viral Panel on Lower Respiratory Tract Specimens. J.Clin.Microbiol, 2014 52(2): 288-290. DOI 10.1128/JC M.02787-13
2Powers J.H, Guerrero M.L, Kline Leidy N., Fairchok M.P.,Rosenberg A. et al. Development of the Flu-PRO: a patient-reported
outcome (PRO) instrument to evaluate symptoms of influenza. BMC Infectious Diseases, 2016, 16:1. DOI 10.1186/s1 2879-015-
1330-0-1-11
INSERT IMAGES 3
Keywords:
influenza,
viral shedding,
Influenza like illness,
Challenge study
Conference:
EUFEMED 2017, London, United Kingdom, 17 May - 19 May, 2017.
Presentation Type:
Oral and Poster
Topic:
EUFEMED 2017 CONFERENCE
Citation:
Mfopou
J,
Memoli
G,
Pillu
H,
De Swert
H and
De Cock
P
(2019). Human challenge studies in healthy volunteers: practical considerations and outcomes of influenza trials.
Front. Pharmacol.
Conference Abstract:
EUFEMED 2017.
doi: 10.3389/conf.fphar.2017.62.00012
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
29 Aug 2017;
Published Online:
25 Jan 2019.
*
Correspondence:
Dr. Heidi De Swert, SGS Belgium NV, Clinical Pharmacology Unit Antwerpen, Antwerp, 2060, Belgium, heidi.deswert@sgs.com