Human rhinoviruses (HRV) are some of the most commonly isolated viral pathogens in people suffering with ‘the common cold’. Over 150 antigenically distinct types of HRV are currently known and these different serotypes span three species: HRV A, HRV B, and HRV C. Rhinovirus infection primarily results in mild upper respiratory tract disease (approximately 50% of all URTIs) and infection rates among young children can be as high as 8–12 times a year. HRV infections are known to be an important predisposing factor to conditions such as sinusitis, otitis media, bronchitis and primary pneumonia, inclusive of secondary bacterial infections. Rhinovirus infections are also linked to asthma exacerbations in children, and this predisposition may persist into adulthood!
Rhinoviruses are known to precipitate serious disease states in the elderly, immune compromised and those with existing respiratory diseases. There is strong epidemiological evidence of a relationship between rhinovirus infection and exacerbation of asthma and chronic obstructive pulmonary disease (COPD). To date, no antiviral agent has been approved in the prevention or treatment of rhinovirus infection and clinical treatment is directed towards addressing symptoms of the disease only (supportive care).
We have an approved and well characterised rhinovirus (HRV-16) that has been used to safely infect individuals in a large number of viral challenge studies carried out at our main containment unit in London.
Markers associated with the primary endpoints for HRV studies, such as infection rates, as measured by viral shedding (peak viral load and viral area under curve (vAUC)), and disease (the clinical syndrome or symptoms associated with experimental infection) are consistent and may be captured from the time of inoculation through to recovery and discharge of the subject.
Volunteers for a rhinovirus study are pre-screened for anti-HRV-16 antibodies to look for immunity to the challenge virus. Naïve or serosusceptible individuals are progressed to further screening relating to protocol associated inclusion and exclusion criteria. Over 373 subjects have been safely infected with HRV to date and this model is widely accepted and practiced across the globe in the investigation of new treatments for the common cold.
Challenge with HRV-16 produces infection in up to 90% of susceptible volunteers. Symptoms usually first appear within 24 hours after inoculation and peak at 48-72 hours. The clinical syndrome is comparable to that reported in natural colds. Approximately one-third of rhinovirus infections, whether natural or experimental, are asymptomatic.
HRV-16 challenge trials may be used to test both prophylactics (i.e. drugs and vaccines that prevent infection and disease) or therapeutics (i.e. mainly drugs used to treat disease once an infection is established).
Over 373 subjects have been safely infected with Human Rhinoviruses to date and this model is widely accepted and practiced across the globe in the investigation of new treatments for the common cold.
Demonstrating efficacy of novel vaccines in the field is time-consuming, costly and associated with risk
Establishing efficacy of antivirals in early clinical trials is challenging Comor
Clinical proof-of concept and dosing finding delivered in a controlled setting
Demonstrating clinical efficacy in early stage field trials is challenging
Clinical proof-of concept and dosing finding delivered in a controlled setting
