Human Rhinoviruses (HRV)

The Model

Human rhinoviruses (HRV) are 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 may also trigger asthma attacks in children, and this predisposition may persist into adulthood.

Rhinoviruses are known to precipitate serious disease states in the elderly and there is strong epidemiological evidence of a relationship between rhinovirus infection and exacerbation of 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).

hVIVO has an approved and well characterised rhinovirus (HRV16) that has been used to safely infect individuals in a large number of viral challenge studies carried out at the main hVIVO 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-HRV16 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 1,500 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.

Validated Human Rhinovirus Model

Challenge with HRV16 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.

HRV16 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 1,500 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.

Vaccines

Conceptual Challenges

Demonstrating efficacy of novel vaccines in the field is time-consuming, costly and associated with risk

  • Initial exposure to virus unknown

  • Variation in circulating strains

  • Large study size and duration

  • Difficult to power for clinical efficacy

  • Seasonality limitations

Flu Vaccines

hVIVO Human Challenge Models: Towards a deeper understanding
  • Effective exploration of vaccine efficacy & correlates of protection

  • Match study design to product mechanism of action

  • Immunological Assays

  • Host Response Analysis

Primary & Secondary Endpoints:
  • Reduction in incidence of symptomatic infection

  • Reduction in disease severity

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Antivirals/Treatments

Conceptual Challenges

Establishing efficacy of antivirals in early clinical trials is challenging

  • Initial exposure to virus unknown

  • Dose ranging and timing difficult

  • Comorbidities and other

Antiviral/Treatments

hVIVO Human Challenge Models: Towards a deeper understanding

Clinical proof-of concept and dosing finding delivered in a controlled setting

  • Study design matched to investigational product mechanism of actions

  • Optimisation of treatment timing

  • Time-dependent measurements of biomarkers

  • Triggered-dosing options (time or virological)

  • Controlled strain exposure

  • Consistent placebo response

  • Efficient resistance monitoring

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Immunomodulators

Conceptual Challenges

Demonstrating clinical efficacy in early stage field trials is challenging

  • Baseline prior to infection unachievable, difficult to establish host response

  • Effect with/without standard of care treatment difficult to establish

  • Large study size and duration

  • Circulating strain variation

  • Biomarker identification difficult

Immunomodulator

hVIVO Human Challenge Models: Towards a deeper understanding

Clinical proof-of concept and dosing finding delivered in a controlled setting

  • Well controlled quarantine environments

  • Baseline well established prior to infection

  • Appropriate for both prophylaxis and treatment

  • Flexible dosing and timing

  • Establish safety & efficacy to impact infected subjects host response

  • Investigate and demonstrate target engagement

  • Controlled combination-treatment with drug and standard of care or antivirals

Human Rhinoviruses (HRV) Scientific Papers / Abstracts