Characterisation of a wild-type influenza (A/H1N1) virus strain as an experimental challenge agent in humans

Virology Journal

Campbell J Bunce⁵  Bertrand Georges⁵  John J Treanor¹  Peter Patriarca²  Jill Makin⁴  Gabriel A Faiman⁵  Sofie Mesens³  James N Francis⁵  Jeannette M Watson⁵ 

[1] University of Rochester Medical Center, 601 Elmwood Avenue, Rochester 14642, NY, USA;Biologics Consulting Group, INC, 1317 King Street, Alexandria 22314, VA, USA;SGS LSS, Clinical Research Unit, Antwerpen, Belgium;Jill Makin Consulting Ltd, 7 Cholmondeley Road, West Kirby CH48 7HB, Wirral, UK;Immune Targeting Systems Ltd, London BioScience Innovation Centre, 2 Royal College Street, London NW1 0NH, UK

关键词: Clinical trial;    Vaccine;    Challenge agent;    Influenza A/H1N1 virus;   

Others  :  1131020
DOI  :  10.1186/s12985-015-0240-5

 received in 2014-07-03, accepted in 2015-01-13,  发布年份 2015

【 摘 要 】

Background

Human challenge models using respiratory viruses such as influenza are increasingly utilised in the development of novel vaccines and anti-viral modalities and can provide preliminary evidence of protection before evaluation in field trials. We describe the results of a clinical study characterising an A/H1N1 influenza challenge virus in humans.

Methods

The challenge agent, influenza A/California/2009 (H1N1), was manufactured under cGMP conditions and characterised in accordance with regulatory guidelines. A dose-ascending open-label clinical study was conducted in 29 healthy young adults screened sero-negative to the challenge strain. Subjects were intranasally inoculated with three increasing doses of virus and physician-reported signs, subjected-reported symptoms, viral shedding and immunological responses were monitored.

Results

A dose-dependent increase in clinical signs and symptoms was observed with 75% of subjects developing laboratory-confirmed illness at the highest inoculum (3.5 × 10⁶ TCID₅₀). At the highest dose, physician or subject-reported signs of infection were classified as mild (all subjects), moderate (50%) and severe (16%) with peak symptoms recorded four days after infection. Clinical signs were correlated with nasal mucus weight (P < .001) and subject-reported symptoms (P < .001). Geometric mean peak viral shedding was log₁₀ 5.16 TCID₅₀ and occurred three days after inoculation with a median duration of five days. The safety profile was such that physiological responses to viral infection were mainly restricted to the upper airways but were not of such severity to be of clinical concern.

Conclusions

A highly characterised wild-type Influenza A/California/2009 (H1N1) virus manufactured for clinical use was shown to induce a good infectivity profile in human volunteers. This clinical challenge model can be used for evaluating potential efficacy of vaccines and anti-viral therapeutics.

Trial registration

NCT02014870 webcite

【 授权许可】

   
2015 Watson et al.; licensee BioMed Central.

【 图 表 】

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