Key result
Inoculation with 10 TCID50 of a newly manufactured GMP Wild-Type HRV-16 challenge virus was safe, pathogenic, and established as the optimal minimum titre to achieve reproducible disease with a 100% infection rate in healthy volunteers.
Why the study?
What is the optimal infectious titre of a newly manufactured GMP Wild-Type HRV-16 challenge virus to yield reproducible infection and mild-to-moderate symptoms in healthy adults?
RCT (n=17)
Single-blind
Permuted block algorithm in a 1:1:1 ratio
No
What is the optimal infectious titre of a newly manufactured GMP Wild-Type HRV-16 challenge virus to yield reproducible infection and mild-to-moderate symptoms in healthy adults?
A newly manufactured GMP Wild-Type HRV-16 challenge virus is safe and pathogenic, with 10 TCID50 identified as the optimal inoculum titre for future human viral challenge models.
Validates low-dose HRV-16 challenge model in volunteers; leaves open utility for antiviral or vaccine trials.
BACKGROUND: Human Rhinovirus infection is an important precursor to asthma and chronic obstructive pulmonary disease exacerbations and the Human Viral Challenge model may provide a powerful tool in studying these and other chronic respiratory diseases. In this study we have reported the production and human characterisation of a new Wild-Type HRV-16 challenge virus produced specifically for this purpose. METHODS AND STOCK DEVELOPMENT: A HRV-16 isolate from an 18 year old experimentally infected healthy female volunteer (University of Virginia Children's Hospital, USA) was obtained with appropriate medical history and consent. We manufactured a new HRV-16 stock by minimal passage in a WI-38 cell line under Good Manufacturing Practice conditions. Having first subjected the stock to rigorous adventitious agent testing and determining the virus suitability for human use, we conducted an initial safety and pathogenicity clinical study in adult volunteers in our dedicated clinical quarantine facility in London. HUMAN CHALLENGE AND CONCLUSIONS: In this study we have demonstrated the new Wild-Type HRV-16 Challenge Virus to be both safe and pathogenic, causing an appropriate level of disease in experimentally inoculated healthy adult volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we have established the minimum inoculum titre required to achieve reproducible disease. We have demonstrated that although inoculation titres as low as 1 TCID50 can produce relatively high infection rates, the optimal titre for progression with future HRV challenge model development with this virus stock was 10 TCID50. Studies currently underway are evaluating the use of this virus as a challenge agent in asthmatics. TRIAL REGISTRATION: ClinicalTrials.gov NCT02522832.
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Fullen et al. (2016) conducted an RCT in Healthy volunteers (serosuitable for HRV-16) (n=17). Wild-Type HRV-16 challenge virus vs. Different dose groups was evaluated on Area under the curve (AUC) of each HRV-16 virus titre load as determined by quantitative polymerase chain reaction (PCR). Inoculation with 10 TCID50 of a newly manufactured GMP Wild-Type HRV-16 challenge virus was safe, pathogenic, and established as the optimal minimum titre to achieve reproducible disease with a 100% infection rate in healthy volunteers.
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